Writing a Gastroparesis Book - And Need Your Help

So, I have been debating on whether or not to write a GP book for years, now. The reason I haven't done so yet is that I remember what it's like not to have health insurance and having to choose between the doctor and medications for the month or rent. However, I have put most of the pertinent information online for free, in my blog. I am working on my outline at present, before I start writing. I want to make sure I cover a lot of ground, and I do not want to lose focus on that.


I don't believe in profiting off of sick people. If this book does sell well, and that's a shot in the dark, I don't need the money so I could send it to a foundation I trust. That's if it sells well. If it does, maybe I can start a 501(c)3 in Atlanta, and expand across GA to help people to get to doctor's appts, fight with their ins companies for them, help them get assistance or something like that. But, if it went to a great cause, like helping others in the community find rides cheaply or at no cost to them, people who could help with insurance hangups, someone to fight for you with your doctor, I mean, I've got a lot of ideas. Please fill out the form below if you are interested in helping me. I will be glad to give credit where credit is due. I really do appreciate this, because I am so tired of losing friends. We need some help and I'm not saying I'm that person, but I'm going to try my best to write something helpful, and maybe it will be published. I hope if it is, that even if they just sell one, I hope it goes to the doctor/scientist who will do research for us. That's my fantasy. I try to remain optimistic. But, the form is below. Just fill that out and again, thank you.
















If you would like to contact me about the questions above, what I should include, and/or if you want to send me your personal stories with photos (I already have photos people have sent me of them before and after GP, which you can do too - or I'm working on a project on my page Gastroparesis - Emily's Stomach, "A Day in the Life of a GPer" which is an event that shows GPers without make up, hair done, no airbrushing or anything, just how we look daily with GP, if you want to send a picture like that. It's up to you).


You can email it to me at: emilysstomach@gmail.com


I know that this research is NOT scientifically accurate because I do not have access to your medical records or anything, but I still have A LOT of your Progressional Timelines that I wanted to graph and insert into the book. I would like you to email your timelines to me, but please let me know it's OK to for me to use your timeline results in my book, let me know how you want me to use your name, or if you would like me to change your name. I need a valid email address you're mailing it from, just in case I have any follow up questions. Your personal information will be respected because I respect privacy.

If this sounds like something you would be interested in (I was trying to find a correlation in us all), you can find out more information about it here:


http://www.emilysstomach.com/2018/10/request-for-gastroparesis-progressional.html


http://www.emilysstomach.com/2013/05/progressional-timeline-of-gastroparesis.html


I'm hoping, that even though my research is thorough, but not scientifically accurate, that someone will read the book who has the power to make this scientifically accurate and start up a research project.




I'm sure I may think of other questions and things later, but I REALLY appreciate any help you guys can spare. I'm going to include a very special thank you page to each person who emails me to help me with this. I believe in giving credit where credit is due. You guys are amazing and I really hope once I sit down to write this, that somehow, it will get to the right person who can do research for better treatments for us. It's not enough to survive, we need to LIVE too!












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Velusetrag and Investigational Medicine Trials for Gastrointestinal Motility Disorders

One of my Gastroparesis friends brought this medication to my attention this morning. A special thanks to Robin for kping me informed about these trials.

Some of these trials were done a year ago, while some of these are up to date. I wanted to include them all so that the progression of these clinical trials can be seen. It gives me hope that there are clinical trials being conducted to help find a less invasive way to help motility in those who have Gastroparesis.



According to Theravance Biopharma,

"Velusetrag is an oral, investigational medicine developed for gastrointestinal motility disorders. It is a highly selective agonist with high intrinsic activity at the human 5-HT4 receptor and is being developed in collaboration with Alfa Wassermann in a Phase 2 program to test its efficacy, safety and tolerability in the treatment of patients with gastroparesis. A Phase 2b study is currently underway following positive top-line results from a Phase 2 proof-of-concept trial.


Axelopran (TD-1211) is a once-daily, oral peripherally active mu opioid receptor antagonist being developed for the treatment of opioid induced constipation (OIC). Axelopran, which has completed long term toxicology studies, is intended to normalize bowel function without impacting analgesia. As a stand-alone treatment, Axelopran has been successfully advanced through Phase 2 studies, demonstrating a rapid restoration of normal bowel function followed by maintenance in OIC patients compared to placebo. Phase 2 study data also shows statistically significant improvements in a range of gastrointestinal symptoms in OIC patients for Axelopran as compared to placebo. We are refining the development and commercial strategy for both single agent and a fixed-dose combination of Axelopran, as well as speaking with potential collaborators.

We believe that pairing Axelopran and an opioid in a fixed-dose combination (FDC) could present an important market opportunity, as it has the potential to provide pain relief without constipation in a single abuse-deterrent pill for patients using opioids on a chronic basis. To this end, we have developed a proprietary spray-coating technology and applied it to the creation of a FDC of Axelopran and controlled-release Oxycodone.

To date, we have successfully conducted a Phase 1 study of our novel Axelopran FDC, showing that our proprietary spray-coating formulation allowed Oxycodone to be coated with Axelopran in a single pill without any modification of oxycodone, its activity or abuse-deterrent characteristics. Based on our work to date, we believe our spray-coating technology is applicable to a broad range of opioids, allowing for a potential FDC platform. We are refining the development and commercial strategy for both single agent and a FDC of Axelopran, as well as speaking with potential collaborators.



TD-8954 is a selective 5-HT4 receptor agonist being investigated for potential use in the treatment of gastrointestinal motility disorders, including enteral feeding intolerance ("EFI"). Millennium Pharmaceuticals, Inc., a wholly-owned subsidiary of Takeda Pharmaceutical Company Limited has a global license, development and commercialization agreement for TD-8954 for potential use in the treatment of gastrointestinal motility disorders, including short-term intravenous use for EFI to achieve early nutritional adequacy in critically ill patients at high nutritional risk, for which TD-8954 received U.S. Food and Drug Administration (FDA) Fast Track Designation.



TD-1473 is an intestinally restricted pan-janus kinase (JAK) inhibitor that has demonstrated a high affinity for each of the JAK family of enzymes (JAK1, JAK2, JAK3 and TYK2). Through the inhibition of these enzymes, TD-1473 interferes with the JAK/STAT signaling pathway and, in turn, modulates the activity of a wide range of pro-inflammatory cytokines. Importantly, as an intestinally restricted treatment, TD-1473 is specifically designed to distribute adequately and exclusively to the tissues of the intestinal tract and to minimize systemic exposure. As such, we believe that this novel approach to JAK inhibition has the potential to treat inflammation in the tissues of the intestinal tract while minimizing the risk of systemic side effects. We are conducting a Phase 1 clinical study of TD-1473."

Image Source: Located on the image.





According to Government Clinical Trials,

"Brief Summary:

This is a multicenter, randomized, double-blind, incomplete block, three period fixed sequence crossover, multicenter, placebo-controlled study. The study will assess three oral doses of velusetrag (5 mg, 15 mg, and/or 30 mg) or placebo, administered once daily in three periods of 1-week duration each, with a 1-week washout period between treatment periods, in subjects with diabetic or idiopathic gastroparesis.

Study 0093 will evaluate the effect of Velusetrag in subjects with diabetic or idiopathic gastroparesis by assessing changes in gastric emptying.

Velusetrag (INN,[1] USAN; previously known as TD-5108) is an experimental drug candidate for the treatment of gastric neuromuscular disorders including gastroparesis, and lower gastrointestinal motility disorders including chronic idiopathic constipation and irritable bowel syndrome.[2] It is a potent, selective, high efficacy 5-HT4 receptor serotonin agonist [3] being developed by Theravance Biopharma[4] and Alfa Wassermann.[5] Velusetrag demonstrates less selectivity for other serotonin receptors, such as 5-HT2 and 5-HT3, to earlier generation 5-HT agonists like cisapride[6] and tegaserod.[7]

In a large clinical trial in patients with chronic idiopathic constipation (n=401), velusetrag statistically and clinically improved the frequency and consistency of complete spontaneous bowel movements (CSBMs) compared to placebo. Doses of 15 and 30 mg were well tolerated compared to placebo.[8]

Velusetrag showed accelerated intestinal and colonic transit after single dosing and accelerated gastric emptying after multiple dosing in healthy volunteer subjects.[9] In addition, velusetrag showed accelerated gastric emptying in patients with diabetic or idiopathic gastroparesis. The proportion of patients who experienced at least a 20% improvement is gastric emptying ranged from 20% to 52% for velusetrag dosed patients and 5% for placebo patients.[10][11]

On December 6, 2016, Theravance Biopharma announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to velusetrag for the treatment of symptoms associated with diabetic and idiopathic Gastroparesis.[12]

As of May 10, 2017, Velusetrag is being studied, at doses of 5, 15 and 30 mg over a 12 week treatment period, for symptomatic improvement in patients with diabetic or idiopathic gastroparesis in the DIGEST study.[13]"

References
"WHO Drug Information, Vol. 24, No. 1, 2010. International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names: List 63" (PDF). World Health Organization. p. 79. Retrieved 26 April 2016.
M. Vazquez-Roque, and M. Camilleri (2011). "Velusetrag". Drugs of the Future. 36 (6): 447–454. doi:10.1358/dof.2011.036.06.1594078.
Smith, JA; Beattie, DT; Marquess, D; Shaw, JP; Vickery, RG; Humphrey, PP (2008). "The in vitro pharmacological profile of TD-5108, a selective 5-HT(4) receptor agonist with high intrinsic activity". Naunyn-Schmiedeberg's archives of pharmacology. 378 (1): 125–37. doi:10.1007/s00210-008-0282-y. PMID 18415081.
"Theravance Biopharma: Programs". Theravance Biopharma. Retrieved 2017-05-10.
"Theravance and Alfa Wassermann Enter Into Agreement to Develop and Commercialize Velusetrag for Gastroparesis". www.sec.gov. Retrieved 2017-05-10.
"Cisapride". Wikipedia. 2017-02-17.
"Tegaserod". Wikipedia. 2017-02-17.
Goldberg, M; Li, YP; Johanson, JF; Mangel, AW; Kitt, M; Beattie, DT; Kersey, K; Daniels, O (2010). "Clinical trial: The efficacy and tolerability of velusetrag, a selective 5-HT4 agonist with high intrinsic activity, in chronic idiopathic constipation - a 4-week, randomized, double-blind, placebo-controlled, dose-response study". Alimentary pharmacology & therapeutics. 32 (9): 1102–12. doi:10.1111/j.1365-2036.2010.04456.x. PMID 21039672.
Manini, ML; Camilleri, M; Goldberg, M; Sweetser, S; McKinzie, S; Burton, D; Wong, S; Kitt, MM; et al. (2010). "Effects of Velusetrag (TD-5108) on gastrointestinal transit and bowel function in health and pharmacokinetics in health and constipation". Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. 22 (1): 42–9, e7–8. doi:10.1111/j.1365-2982.2009.01378.x. PMC 2905526 Freely accessible. PMID 19691492.
"Theravance Biopharma Presents Positive Phase 2 Study Data on Velusetrag (TD-5108) for Treatment of Gastroparesis in "Poster of Distinction" at Digestive Disease Week (DDW) 2015 (NASDAQ:TBPH)". investor.theravance.com. Retrieved 2017-05-10.
House, SA Editor Douglas W. (2015-05-18). "Theravance's velusetrag performs well in gastroparesis study". Seeking Alpha. Retrieved 2017-05-10.
Morales, Sysy (2016-12-18). "FDA Gives Fast Track Designation for Gastroparesis Treatment". Diabetes Daily. Retrieved 2017-05-10.
"The Diabetic and Idiopathic Gastroparesis Efficacy, Safety, and Tolerability (DIGEST) Study". ClinicalTrials.gov. Retrieved 26 April 2016.





As of right now, these are the only options available to people battling Gastroparesis:

Source: Located on image.




According to the U.S. Library of National Medicine,

"Velusetrag has been used in trials studying the treatment of Gastroparesis and Alzheimer's Disease. It is a highly selective serotonin receptor agonist effective in patients with chronic constipation. It is being developed by Theravance. Velusetrag was discovered by Theravance through the application of its multivalent drug design in a research program dedicated to finding new treatments for GI motility disorders."

Source: unknown.



As of August of 2017, According to Theravance Biopharma,

"Theravance Biopharma Announces Positive Top-Line Results from Phase 2b Study of Velusetrag (TD-5108) in Patients with Gastroparesis: Improvements in Symptoms and Normalized Gastric Emptying Demonstrated in both Diabetic and Idiopathic Gastroparesis Patients



Theravance Biopharma, Inc.
Aug 02, 2017, 07:00 ET


DUBLIN, Ireland, Aug. 2, 2017 /PRNewswire/ -- Theravance Biopharma, Inc. (NASDAQ: TBPH) ('Theravance Biopharma' or the 'Company') today announced positive results from a 12-week, Phase 2b study of velusetrag (TD-5108), an oral investigational drug in development for the treatment of patients with diabetic and idiopathic gastroparesis. Top-line results from the study demonstrated statistically significant improvements in gastroparesis symptoms and gastric emptying in patients receiving 5 mg of velusetrag as compared to placebo. Additionally, velusetrag was shown to be generally well-tolerated, with 5 mg and placebo having comparable rates of adverse events (AEs) and serious adverse events (SAEs).

The study was conducted in 232 patients with either diabetic or idiopathic gastroparesis who received either velusetrag (5, 15 or 30 mg) or placebo, administered orally as a once daily dose. After four weeks of dosing, when the primary assessments were made, patients in the 5 mg velusetrag treatment arm demonstrated statistically significant improvements in symptom scores compared to placebo in two separate patient reported outcome (PRO) tools: the Gastroparesis Cardinal Symptom Index (GCSI) (nominal p = 0.0327) and the Gastroparesis Rating Scale (GRS) (nominal p = 0.0159). Improvements in GRS total score were maintained at 12 weeks of treatment (nominal p = 0.0427). Compared to placebo, patients in the 5 mg treatment arm also demonstrated statistically significant improvements in gastric emptying time (nominal p < 0.001) and in individual disease-specific symptom scores including post-prandial fullness/early satiety, bloating and upper abdominal pain (all nominal p < 0.05). Importantly, the symptom improvements seen with 5 mg of velusetrag were observed in both diabetic and idiopathic gastroparesis patients. The primary endpoint analysis included a pre-specified analysis of each dose against placebo to report nominal p-values. The analysis also included multiplicity adjustments of p-values to account for three dose comparisons to placebo. Patients in the 15 and 30 mg velusetrag study arms did not demonstrate nominally statistically significant improvements in gastroparesis symptoms versus placebo, possibly due to an increased frequency in gastrointestinal side effects at these doses that may have been caused by rapid emptying of the stomach. The lack of dose response resulted in a lack of statistical significance across the three doses when adjusted for multiplicity. As a result, the statistical comparisons for the 5 mg dose are not adjusted for multiple comparisons, and all are quoted as nominal. Of note, the 15 mg and 30 mg doses remained highly statistically significant compared to placebo in gastric emptying time (nominal p < 0.001), as measured by scintigraphy. "We are very encouraged by the results of this study as they demonstrate not only consistent evidence of improved gastric emptying but also meaningful improvement in gastroparesis symptoms following treatment with 5 mg of velusetrag. The findings from this study demonstrate that a 5 mg dose was sufficient to ameliorate the symptoms of gastroparesis. We believe that these findings provide clear evidence of the potential benefit of velusetrag in patients with gastroparesis, a debilitating disease in significant need of therapeutic innovation," said Brett Haumann, MD, Chief Medical Officer of Theravance Biopharma. "We are now preparing to meet with regulators to discuss the next phase in our development plan." Velusetrag was shown to be generally well-tolerated, with rates of AEs and SAEs comparable between the 5 mg dose and placebo. The most commonly reported AEs across all groups (active treatment and placebo) were diarrhea, nausea and headache. Consistent with velusetrag's mechanism of action, patients receiving treatment demonstrated higher rates of diarrhea and nausea/vomiting than those receiving placebo, and these rates were numerically highest in the 15 and 30 mg arms of the study. Diabetic subjects treated with velusetrag generally maintained adequate glucose control throughout the study, and there were no episodes of hyperglycemia reported. There was no difference in the number of cardiac adverse events, with four events reported in placebo subjects and four events reported in all velusetrag treated subjects. There were no deaths reported in the study. Theravance Biopharma intends to present additional results from the study at upcoming medical conferences, as well as in appropriate scientific journals. Theravance Biopharma will hold a conference call and webcast presentation today at 8:00 am ET to discuss the results of the Phase 2b study of velusetrag. To participate in the live call by telephone, please dial (855) 296-9648 from the U.S., or (920) 663-6266 for international callers, using the confirmation code 61886684. To listen to the conference call live via the internet please visit Theravance Biopharma's website at www.theravance.com, under the Investor Relations section, Presentations and Events. To listen to the live call please go to Theravance Biopharma's website 15 minutes prior to its start to register, download, and install any necessary audio software. A replay of the conference call will be available on Theravance Biopharma's website through September 2, 2017. An audio replay will also be available through 8:00 am ET on August 9, 2017 by dialing (855) 859-2056 from the U.S., or (404) 537-3406 for international callers, using the confirmation code 61886684. [**Blogger's NOTE: Call has already been done as of today] About the Phase 2b Study

The study was a multicenter, double-blind, placebo-controlled, parallel group Phase 2b characterizing the impact on symptoms and gastric emptying of multiple doses of velusetrag administered once daily over 12 weeks of therapy. The study enrolled 232 subjects with diabetic or idiopathic gastroparesis with documented gastric delay, by either gastric emptying scintigraphy (GES) or gastric emptying breath test (GEBT), and documented symptoms prior to and throughout the baseline period. Two daily patient reported outcomes (PRO) tools were used to characterize symptom change: the Gastroparesis Cardinal Symptom Index (GCSI), which assessed the severity of three cardinal symptom domains; and the Gastroparesis Rating Scale (GRS), which assessed severity, frequency and timing of seven symptom domains, including the three symptom domains in the GCSI. GRS is a proprietary PRO tool being developed by the Company with academic collaboration. The primary endpoint in the study was mean GCSI score at the end of week 4 of the treatment period.


About Gastroparesis

Gastroparesis is a disorder characterized by delayed gastric emptying and symptoms of gastric retention in the absence of mechanical obstruction. In the United States, it is estimated to affect approximately six million individuals, or 1.8% of the population, and includes two major sub-classes: those with diabetic gastroparesis (29% of the overall gastroparesis population) and those with idiopathic gastroparesis (36%).1 Symptoms of gastroparesis are variable but typically include nausea, vomiting, early satiety, postprandial bloating/fullness or upper abdominal discomfort. Severe cases may also suffer from dehydration, electrolyte disturbances, weight loss and malnutrition. There is also a correlation between severity of symptoms and impairment of quality of life.2


About Velusetrag

Velusetrag is an oral, once-daily investigational medicine discovered internally and developed for gastrointestinal motility disorders. The compound has been granted Fast Track designation by the U.S Food and Drug Administration (FDA) for the treatment of symptoms associated with idiopathic and diabetic gastroparesis.

Velusetrag is a highly selective agonist with high intrinsic activity at the human 5-HT4 receptor. 5-hydroxytryptamine receptor 4 (5-HT4) agonists are established as gastrointestinal (GI) prokinetic agents for the treatment of GI tract dysfunction, such as chronic constipation. Velusetrag (or TD-5108) is a 5-HT4 receptor agonist that demonstrates high in vitro intrinsic activity and selectivity for the 5-HT4 receptor and has no significant affinity for all other receptor types, ion channels, or enzymes tested.

A previous Phase 2 trial of velusetrag showed that all three doses of velusetrag (5, 15 and 30 mg) reduced gastric emptying time (GE t1/2) compared to placebo in patients with either diabetic or idiopathic gastroparesis. The completed Phase 2 trial was the first study to evaluate gastric emptying, a diagnostic criterion for gastroparesis, in a patient population including both diabetic and idiopathic gastroparesis patients, as opposed to diabetic gastroparesis patients only. In addition, velusetrag has completed a 400-patient Phase 2 proof-of-concept study in chronic idiopathic constipation, demonstrating statistically significant prokinetic activity at all three doses tested in that study.

Velusetrag is being developed by Theravance Biopharma in collaboration with Alfasigma (S.p.A.) ("Alfasigma"). Under the terms of the agreement, Alfasigma has an exclusive option to develop and commercialize velusetrag in the European Union, Russia, China, Mexico and certain other countries, while Theravance Biopharma retains full rights to velusetrag in the United States, Canada, Japan and certain other countries.


About Theravance Biopharma

Theravance Biopharma is a diversified biopharmaceutical company with the core purpose of creating medicines that make a difference in the lives of patients suffering from serious illness.

Our pipeline of internally discovered product candidates includes potential best-in-class medicines to address the unmet needs of patients being treated for serious conditions primarily in the acute care setting. VIBATIV® (telavancin), our first commercial product, is a once-daily dual-mechanism antibiotic approved in the U.S., Europe and certain other countries for certain difficult-to-treat infections. Revefenacin (TD-4208) is a long-acting muscarinic antagonist (LAMA) being developed as a potential once-daily, nebulized treatment for chronic obstructive pulmonary disease (COPD). Our neprilysin (NEP) inhibitor program is designed to develop selective NEP inhibitors for the treatment of a range of major cardiovascular and renal diseases, including acute and chronic heart failure, hypertension and chronic kidney diseases, such as diabetic nephropathy. Our research efforts are focused in the areas of inflammation and immunology, with the goal of designing medicines that provide targeted drug delivery to tissues in the lung and intestinal tract in order to maximize patient benefit and minimize risk. The first program to emerge from this research is designed to develop intestinally restricted pan-Janus kinase (JAK) inhibitors for the treatment of a range of inflammatory intestinal diseases.

In addition, we have an economic interest in future payments that may be made by Glaxo Group Limited or one of its affiliates (GSK) pursuant to its agreements with Innoviva, Inc. relating to certain drug development programs, including the Closed Triple (the combination of fluticasone furoate, umeclidinium, and vilanterol), currently in development for the treatment of COPD and asthma.

For more information, please visit www.theravance.com.


THERAVANCE®, the Cross/Star logo, and VIBATIV® are registered trademarks of the Theravance Biopharma group of companies. Trademarks, trade names or service marks of other companies appearing on this press release are the property of their respective owners.

This press release and the conference call will contain contains certain 'forward-looking' statements as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding, among other things, statements relating to goals, plans, objectives, expectations and future events. Theravance Biopharma intends such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. Examples of such statements include statements relating to: the company's strategies, plans and objectives, the company's regulatory strategies and timing of clinical studies, the potential benefits and mechanisms of action of the company's product and product candidates, the company's expectations for product candidates through development, potential regulatory approval and commercialization (including their potential as components of combination therapies) and the company's expectations for product sales. These statements are based on the current estimates and assumptions of the management of Theravance Biopharma as of the date of the press release and are subject to risks, uncertainties, changes in circumstances, assumptions and other factors that may cause the actual results of Theravance Biopharma to be materially different from those reflected in the forward-looking statements. Important factors that could cause actual results to differ materially from those indicated by such forward-looking statements include, among others, risks related to: delays or difficulties in commencing or completing clinical studies, the potential that results from clinical or non-clinical studies indicate the company's product candidates are unsafe or ineffective (including when our product candidates are studied in combination with other compounds),the feasibility of undertaking future clinical trials for our product candidates based on FDA policies and feedback, dependence on third parties to conduct clinical studies, delays or failure to achieve and maintain regulatory approvals for product candidates, risks of collaborating with or relying on third parties to discover, develop and commercialize product and product candidates, and risks associated with establishing and maintaining sales, marketing and distribution capabilities with appropriate technical expertise and supporting infrastructure. Other risks affecting Theravance Biopharma are described under the heading 'Risk Factors' contained in Theravance Biopharma's Form 10-Q filed with the Securities and Exchange Commission (SEC) on May 9, 2017 and Theravance Biopharma's other filings with the SEC. In addition to the risks described above and in Theravance Biopharma's filings with the SEC, other unknown or unpredictable factors also could affect Theravance Biopharma's results. No forward-looking statements can be guaranteed and actual results may differ materially from such statements. Given these uncertainties, you should not place undue reliance on these forward-looking statements. Theravance Biopharma assumes no obligation to update its forward-looking statements on account of new information, future events or otherwise, except as required by law.

References:

1 American Gastroenterological Association. "Technical Review on the Diagnosis and Treatment of Gastroparesis." http://www.gastrojournal.org/article/S0016-5085(04)01634-8/fulltext. Published online July 27, 2005.

2 Journal of Neurogastroenterology and Motility. "Prevalence of Hidden Gastroparesis in the Community: The Gastroparesis 'Iceberg'." http://www.jnmjournal.org/journal/view.html?doi=10.5056/jnm.2012.18.1.34. Published online January 16, 2012."

In conclusion, these trials look promising. Hopefully, soon, we will have more treatments for Gastroparesis. There are several clinical trials being conducted that show promising results. I have more clinical trials in another blog article I wrote, which you can find here: http://www.emilysstomach.com/2018/06/fda-accepts-cardiac-safety-trial-for.html. I really hope that these trials continue to show promise, because as of right now, there are medications that can cause permanent neurological side effects, or very extreme measures like stomach surgery or the gastric pacemaker to help with Gastroparesis. We need something less invasive that will help to increase our motility. My friend Paul recommended this article: https://coatings.specialchem.com/tech-library/article/hsp-science-based-formulation-for-coatings for more information. He says,"After a week of research I have put together comprehensive article on "'HSP for Coatings.'" It's pwtj ceckok -

A Collection of Gastroparesis Medical Studies and Research

This article is from 2016, but I still think it's worth sharing. I also want to say that I will keep updating this article for any new studies, research, and new treatments for Gastroparesis. I want it to stay current and it might help someone.

Source: Unknown





According to EMORY:

"Minimally Invasive Procedure for Gastroparesis Shows Promising Results


A minimally invasive procedure at Emory University Hospital is showing promise in patients with gastroparesis, a digestive disorder in which the stomach does not empty food in a normal manner. The results of two small Emory studies were presented recently at the American College of Gastroenterology (ACG) in Las Vegas, where the researchers accepted the 2016 ACG Governor’s Award for Excellence in Clinical Research and the ACG Presidential Poster Award.

Gastroparesis occurs in diabetic patients and other patients with no underlying causes, where the muscles of the stomach and intestines do not properly function. Food then moves slowly or stops moving through the digestive tract.

In one study, Emory researchers performed a retrospective review of data in 10 patients who underwent gastric peroral endoscopic pyloromyotomy or G-POEM for gastroparesis. G-POEM involves guiding a small knife through an endoscope into the submucosal tunnel. Once there, an incision is made in the pyloric ring muscle to release the tightness of that muscle and normalize gastric emptying.

"In these 10 patients, clinical success was defined by improvement of symptoms measured with a decrease in the Gastroparesis Cardinal Score Index (GCSI) and no recurrent hospitalization," says Sunil Dacha, MD, assistant professor of medicine in the Division of Digestive Diseases, Emory University School of Medicine, and a former advanced endoscopic fellow with Qiang Cai, MD, professor of medicine in the Division of Digestive Diseases at Emory, who is an expert in the minimally invasive procedure. "We found G-POEM was clinically successful in eight of the 10 patients (80 percent) with a decrease in mean GCSI from 30.1 prior to the procedure to 12.8 at follow-up."

Gastric emptying studies were obtained on seven of the 10 patients following G-POEM. Results showed gastric emptying had normalized in five patients and improvements were noted in two other patients. Mean four-hour gastric retention decreased from 62.5 percent to 25.4 percent after G-POEM, indicating the stomach emptied much faster at four hours after a meal. A follow-up questionnaire also highlighted significant improvement in quality of life in several areas.

One patient in the study had no response and required hospitalization 15 days after G-POEM and another patient showed no improvement in symptoms.

A second study, presented at the ACG by Abhinav Koul, MD, a former Emory medical resident who worked with Cai, detailed three patients with gastroparesis who had failed gastric electrical stimulation, but showed improvement following G-POEM. Electrical stimulation of the gastric nerves by a small implantable device is one treatment option for patients with gastroparesis. In this retrospective study, Emory researchers determined G-POEM can be performed safely as a salvage therapy for patients with gastroparesis who failed treatment with a gastric stimulator.

The study also found G-POEM improved symptoms (mean GCSI decreased by an average of 64 percent from 27 to 10) as well as gastric emptying (60.6 percent to 18.3 percent mean average) in these patients. However, more data is needed to further define the role of G-POEM in this challenging patient population. Koul is now a clinical assistant professor at the Medical College of Georgia-UGA Medical Partnership at Athens Regional Medical Center.

"G-POEM is showing some positive results as an additional therapeutic modality for patients with gastroparesis who suffer with delayed gastric emptying," says Cai, who also serves as the director of the Advanced Endoscopy Fellowship at Emory. "We are only one of a few centers in the U.S. offering this specialized procedure."

In 2012, Cai started the POEM procedure at Emory University Hospital for patients with achalasia, a disorder of the esophagus that causes swallowing difficulties. He then developed the G-POEM program at the hospital, in hopes of finding alternative treatments for patients with gastroparesis."

Source: The above article



There is a new medication called, "Prucalopride," that is in trials right now for Gastroparesis. One of my friends brought this to my attention so I wanted to add it to this article. According to https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3263983/pdf/10.1177_1756283X11423706.pdf,

According to THE CLEVELAND CLINIC:

"New Program Offers Multidisciplinary Treatment and Hope to Patients with Gastroparesis


For patients with gastroparesis, long-term relief from nausea, vomiting and bloating may have seemed like an impossible dream. However, medical experts have discovered the secret to conquering this chronic condition. Effective patient care for gastroparesis requires innovative treatment combined with the expertise of physicians from multiple disciplines.


Challenges of traditional treatment

The most common treatments for gastroparesis include pain management, medication and surgery. However, using just one of these treatments is unlikely to relieve the patient’s symptoms. Physicians must consider the patient’s overall health, including diet, psychology and pain levels. When patients receive treatments from physicians in multiple disciplines, the overall treatment plan usually lacks cohesion and focus.

Because gastroparesis is such a rare disorder, few medical centers have had enough exposure to patients with this condition to develop effective treatment plans. Plus, the therapies are evolving so rapidly that many hospitals are struggling to keep up with the changes.

As a result, gastroparesis patients may spend a lot of time and money on various physicians and specialists who are not addressing their condition from a holistic viewpoint. A history of poor, ineffective treatments has left many gastroparesis patients very frustrated.


Convenient, multidisciplinary care

At the Digestive Disease & Surgical Institute, gastroparesis is the number one reason for patient referrals. This influx of patients gives physicians abundant opportunities to gain practical experience diagnosing and treating gastroparesis.

Currently led by Surgical Endoscopist John Rodriguez, MD, and Gastroenterologist Michael Cline, DO, the Gastroparesis Clinic offers a centralized place for patients to consult multiple specialists, including psychologists, gastroenterologists, pain specialists, nutritionists and surgical endoscopists. 'Because they have experience working together to support patients with gastroparesis, they know what works and what doesn’t,' explains Director of Surgical Endoscopy Matthew D. Kroh, MD. 'They also know whom to consult when they’ve hit a roadblock in the process.'

Following the patient’s initial appointments, the multidisciplinary team develops a treatment plan that’s tailored to every aspect of the patient’s condition. Throughout treatment, care team members stay in touch with each other and the patient, making adjustments as needed.The convenience of the Gastroparesis Clinic also contributes to patient ease. 'Our patients can schedule their appointments with multiple doctors over the course of one or two days, making scheduling one less thing that they have to worry about,' says Dr. Kroh. This is especially helpful for patients who must travel a considerable distance to seek treatment at Cleveland Clinic.



POP: Using surgical tools in endoscopic applications

The Digestive Disease & Surgical Institute’s Developmental Endoscopy Group recently used POP to treat several patients with gastroparesis. Led by Dr. Kroh and Medical Director Mansour Parsi, MD, MPH, these experts in gastroenterology, general surgery, colorectal surgery and interventional endoscopy work together to implement and refine POP procedures.

During POP, the physician cuts the pylorus, a muscular valve that empties the stomach, without surgery. Using advanced endoscopic tools, the entire procedure is performed through the mouth without the need for incisions. After the lining of the stomach is opened, only the pylorus is divided under high-definition vision, improving the emptying ability of the stomach.

By using an endoscopic method, the physician decreases the morbidity associated with laparoscopic surgery while delivering the same effectiveness for the patient. Traditional laparoscopic methods for dividing the pylorus muscle can result in pain from the incisions, herniation or leakage from the closure. POP eliminates the access trauma induced by open and laparoscopic surgery.

Many of the new endoscopic instruments and knives used in POP originated in Japan where physicians used them to remove early cancers. These pioneers in minimally invasive technology created a platform that allows Cleveland Clinic physicians to use surgical tools in innovative endoscopic applications.



Promising patient outcomes

The initial patient outcomes for POP procedures performed by the Digestive Disease & Surgical Institute look very promising. Immediately following treatment, physicians have noted symptomatic improvement as well as gastric emptying improvement.

'To finally be able to manage the full spectrum of care for patients who have suffered with gastroparesis for so many years is very rewarding,' says Dr. Kroh. 'Giving these patients the support and treatment they really need — and watching them steadily improve — makes it all worthwhile.'



Ongoing training and development

According to Dr. Kroh, the Developmental Endoscopy Group is busy training physicians in digestive disease fellowship programs at Cleveland Clinic to adopt the latest laparoscopic and endoscopic techniques. “When they graduate, these physicians will be fully prepared to help other hospitals implement innovative treatment programs for gastroparesis,” he reveals.

The Gastroparesis Clinic is a valuable resource for digestive disease physicians who lack experience in treating gastroparesis. 'We would love to have administrators or physicians from other hospitals work with us and do case observations through our clinic,' explains Dr. Kroh. 'This training would help them benefit from our expertise and put our technologies and treatments into practice.'

In support of the Gastroparesis Clinic, the Developmental Endoscopy Group will continue to develop laparoscopic and endoscopic procedures to treat patients with gastroparesis and other digestive disorders.

Source: Article above




According to HEALIO (from 2016):

"Latest Gastroparesis News, Research for Health Care Providers


An estimated 5 million Americans have gastroparesis, according to the International Foundation for Functional Gastrointestinal Disorders.

Michael Camilleri, MD, and colleagues detailed the management of gastroparesis in guidelines issued by the American College of Gastroenterology.

'Gastroparesis is identified in clinical practice through the recognition of the clinical symptoms and documentation of delayed gastric emptying,' they wrote. 'Symptoms from gastroparesis include nausea, vomiting, early satiety, postprandial fullness, bloating, and upper abdominal pain. Management of gastroparesis should include assessment and correction of nutritional state, relief of symptoms, improvement of gastric emptying and, in diabetics, glycemic control.'

In a statement for the record, Sen. Tammy Baldwin, D-Wis., brought attention to the condition, which can lead to issues in managing blood glucose levels, dehydration and malnutrition.

'While there is no cure for gastroparesis, some treatments, such as dietary measures, medications, procedures to maintain nutrition, and surgery, can help reduce symptoms,' she said. 'Unfortunately, gastroparesis is a poorly understood condition and so patients often suffer from delayed diagnosis, treatment and management of this disorder. As such, further research and education are needed to improve quality of life for this patient population.'

Relamorelin improves diabetic gastroparesis symptoms

Adults with diabetic gastroparesis experienced accelerated gastric emptying and reduced vomiting with 10 µg of subcutaneous relamorelin administered twice daily, according to phase 2 trial data. Read more.

G-POEM promising minimally invasive treatment for refractory gastroparesis

Mouen A. Khashab, MD, associate professor of medicine and director of therapeutic endoscopy at Johns Hopkins Hospital in Baltimore, discusses positive results from a study of gastric peroral endoscopic myotomy.

FDA issues draft guidance on clinical evaluation of gastroparesis drugs

'The purpose of this guidance is to assist sponsors in the clinical development of drugs for the treatment of diabetic and idiopathic gastroparesis,' the FDA wrote in the draft guidance. 'Specifically, this guidance addresses the [FDA’s] current thinking regarding clinical trial designs and clinical endpoint assessments to support development of gastroparesis drugs,' for which there is an “urgent medical need.'

Age, sex, obesity among factors that affect outcomes in gastroparesis

A recent study found that less than a third of patients with gastroparesis had significant symptom relief after treatment, and identified a number of independent predictors of symptom reduction. Read more.

FDA approves breath test for diagnosis of gastroparesis

The FDA today approved the Gastric Emptying Breath Test, or GEBT, a novel noninvasive diagnostic for gastroparesis.


References:

Camilleri M, et al. Am J Gastroenterol. 2013;doi: 10.1038/ajg.2012.373.

Statement in the Record Recognizing Gastroparesis Awareness Month. International Foundation for Functional Gastrointestinal Disorders website. Accessed August 18, 2016. (**Note, you can read more about topics and procedures in the article itself**)

Source: My friend Alley made this image.



Here are some additional blog articles that may help:

GASTROPARESIS PATIENTS VS DRUG SEEKERS.

GASTROPARESIS VS EATING DISORDERS.

INFORMATION ABOUT THE VAGUS NERVE.

The Brain in Your Gut

I know a lot of people with gastroparesis have memory issues, myself included. So, what causes this? How does our brain chemistry change when you have gastroparesis? Sleep deprivation, malnutrition, and medication can play a big part in altering our brain chemistry but I wanted to dig a bit deeper to see what else can change our body's brain chemistry, and why it affects us so harshly.

Credit: ISTOCKPHOTO/ERAXION


According to Cal Tech http://www.caltech.edu/news/microbes-help-produce-serotonin-gut-46495,

"Although serotonin is well known as a brain neurotransmitter, it is estimated that 90 percent of the body's serotonin is made in the digestive tract. In fact, altered levels of this peripheral serotonin have been linked to diseases such as irritable bowel syndrome, cardiovascular disease, and osteoporosis.

'More and more studies are showing that mice or other model organisms with changes in their gut microbes exhibit altered behaviors,' explains Elaine Hsiao, research assistant professor of biology and biological engineering and senior author of the study. 'We are interested in how microbes communicate with the nervous system. To start, we explored the idea that normal gut microbes could influence levels of neurotransmitters in their hosts.'

Peripheral serotonin is produced in the digestive tract by enterochromaffin (EC) cells and also by particular types of immune cells and neurons. Hsiao and her colleagues first wanted to know if gut microbes have any effect on serotonin production in the gut and, if so, in which types of cells. They began by measuring peripheral serotonin levels in mice with normal populations of gut bacteria and also in germ-free mice that lack these resident microbes.

The researchers found that the EC cells from germ-free mice produced approximately 60 percent less serotonin than did their peers with conventional bacterial colonies. When these germ-free mice were recolonized with normal gut microbes, the serotonin levels went back up—showing that the deficit in serotonin can be reversed.

'EC cells are rich sources of serotonin in the gut. What we saw in this experiment is that they appear to depend on microbes to make serotonin—or at least a large portion of it,' says Jessica Yano, first author on the paper and a research technician working with Hsiao.

The researchers next wanted to find out whether specific species of bacteria, out of the diverse pool of microbes that inhabit the gut, are interacting with EC cells to make serotonin.

After testing several different single species and groups of known gut microbes, Yano, Hsiao, and colleagues observed that one condition—the presence of a group of approximately 20 species of spore-forming bacteria—elevated serotonin levels in germ-free mice. The mice treated with this group also showed an increase in gastrointestinal motility compared to their germ-free counterparts, and changes in the activation of blood platelets, which are known to use serotonin to promote clotting.

Wanting to home in on mechanisms that could be involved in this interesting collaboration between microbe and host, the researchers began looking for molecules that might be key. They identified several particular metabolites—products of the microbes' metabolism—that were regulated by spore-forming bacteria and that elevated serotonin from EC cells in culture. Furthermore, increasing these metabolites in germ-free mice increased their serotonin levels.

Previous work in the field indicated that some bacteria can make serotonin all by themselves. However, this new study suggests that much of the body's serotonin relies on particular bacteria that interact with the host to produce serotonin, says Yano. 'Our work demonstrates that microbes normally present in the gut stimulate host intestinal cells to produce serotonin,' she explains.

'While the connections between the microbiome and the immune and metabolic systems are well appreciated, research into the role gut microbes play in shaping the nervous system is an exciting frontier in the biological sciences,' says Sarkis K. Mazmanian, Luis B. and Nelly Soux Professor of Microbiology and a coauthor on the study. 'This work elegantly extends previous seminal research from Caltech in this emerging field'.

Additional coauthor Rustem Ismagilov, the Ethel Wilson Bowles and Robert Bowles Professor of Chemistry and Chemical Engineering, adds, 'This work illustrates both the richness of chemical interactions between the hosts and their microbial communities, and Dr. Hsiao's scientific breadth and acumen in leading this work.'

Serotonin is important for many aspects of human health, but Hsiao cautions that much more research is needed before any of these findings can be translated to the clinic.

'We identified a group of bacteria that, aside from increasing serotonin, likely has other effects yet to be explored,' she says. 'Also, there are conditions where an excess of peripheral serotonin appears to be detrimental.'

Although this study was limited to serotonin in the gut, Hsiao and her team are now investigating how this mechanism might also be important for the developing brain. 'Serotonin is an important neurotransmitter and hormone that is involved in a variety of biological processes. The finding that gut microbes modulate serotonin levels raises the interesting prospect of using them to drive changes in biology,' says Hsiao.

The work was published in an article titled 'Indigenous Bacteria from the Gut Microbiota Regulate Host Serotonin Biosynthesis.' In addition to Hsiao, Yano, Mazmanian, and Ismagilov, other Caltech coauthors include undergraduates Kristie Yu, Gauri Shastri, and Phoebe Ann; graduate student Gregory Donaldson; postdoctoral scholar Liang Ma. Additional coauthor Cathryn Nagler is from the University of Chicago."

Image Credit: http://i2.wp.com/sitn.hms.harvard.edu/wp-content/uploads/2016/08/Gut-Brain-Microbe-Figures_FINAL.png





This is an interesting study considering that Gastroparesis/DTP is slow to little to no motility, depending on how severe it is in each person affected with it. If 90 percent of serotonin is produced in the stomach, what happens to that serotonin when the motility is limited or the stomach is removed? Could that be a link to depression in people with Gastroparesis? Scientific American believes that psychiatry may have to readjust to consider just that in the years to come as discussed below.



According to Scientific American https://www.scientificamerican.com/article/gut-second-brain/,

"As Olympians go for the gold in Vancouver, even the steeliest are likely to experience that familiar feeling of 'butterflies' in the stomach. Underlying this sensation is an often-overlooked network of neurons lining our guts that is so extensive some scientists have nicknamed it our 'second brain'.

A deeper understanding of this mass of neural tissue, filled with important neurotransmitters, is revealing that it does much more than merely handle digestion or inflict the occasional nervous pang. The little brain in our innards, in connection with the big one in our skulls, partly determines our mental state and plays key roles in certain diseases throughout the body.

Although its influence is far-reaching, the second brain is not the seat of any conscious thoughts or decision-making.

'The second brain doesn't help with the great thought processes…religion, philosophy and poetry is left to the brain in the head,' says Michael Gershon, chairman of the Department of Anatomy and Cell Biology at New York–Presbyterian Hospital/Columbia University Medical Center, an expert in the nascent field of neurogastroenterology and author of the 1998 book The Second Brain (HarperCollins).

Technically known as the enteric nervous system, the second brain consists of sheaths of neurons embedded in the walls of the long tube of our gut, or alimentary canal, which measures about nine meters end to end from the esophagus to the anus. The second brain contains some 100 million neurons, more than in either the spinal cord or the peripheral nervous system, Gershon says.

This multitude of neurons in the enteric nervous system enables us to 'feel' the inner world of our gut and its contents. Much of this neural firepower comes to bear in the elaborate daily grind of digestion. Breaking down food, absorbing nutrients, and expelling of waste requires chemical processing, mechanical mixing and rhythmic muscle contractions that move everything on down the line.

Thus equipped with its own reflexes and senses, the second brain can control gut behavior independently of the brain, Gershon says. We likely evolved this intricate web of nerves to perform digestion and excretion 'on site,' rather than remotely from our brains through the middleman of the spinal cord. 'The brain in the head doesn't need to get its hands dirty with the messy business of digestion, which is delegated to the brain in the gut,' Gershon says. He and other researchers explain, however, that the second brain's complexity likely cannot be interpreted through this process alone.

'The system is way too complicated to have evolved only to make sure things move out of your colon,' says Emeran Mayer, professor of physiology, psychiatry and biobehavioral sciences at the David Geffen School of Medicine at the University of California, Los Angeles (U.C.L.A.). For example, scientists were shocked to learn that about 90 percent of the fibers in the primary visceral nerve, the vagus, carry information from the gut to the brain and not the other way around. "Some of that info is decidedly unpleasant," Gershon says.

The second brain informs our state of mind in other more obscure ways, as well. 'A big part of our emotions are probably influenced by the nerves in our gut,' Mayer says. Butterflies in the stomach—signaling in the gut as part of our physiological stress response, Gershon says—is but one example. Although gastrointestinal (GI) turmoil can sour one's moods, everyday emotional well-being may rely on messages from the brain below to the brain above. For example, electrical stimulation of the vagus nerve—a useful treatment for depression—may mimic these signals, Gershon says.

Given the two brains' commonalities, other depression treatments that target the mind can unintentionally impact the gut. The enteric nervous system uses more than 30 neurotransmitters, just like the brain, and in fact 95 percent of the body's serotonin is found in the bowels. Because antidepressant medications called selective serotonin reuptake inhibitors (SSRIs) increase serotonin levels, it's little wonder that meds meant to cause chemical changes in the mind often provoke GI issues as a side effect. Irritable bowel syndrome—which afflicts more than two million Americans—also arises in part from too much serotonin in our entrails, and could perhaps be regarded as a "mental illness" of the second brain.

Scientists are learning that the serotonin made by the enteric nervous system might also play a role in more surprising diseases: In a new Nature Medicine study published online February 7, a drug that inhibited the release of serotonin from the gut counteracted the bone-deteriorating disease osteoporosis in postmenopausal rodents. (Scientific American is part of Nature Publishing Group.) 'It was totally unexpected that the gut would regulate bone mass to the extent that one could use this regulation to cure—at least in rodents—osteoporosis,' says Gerard Karsenty, lead author of the study and chair of the Department of Genetics and Development at Columbia University Medical Center.

Serotonin seeping from the second brain might even play some part in autism, the developmental disorder often first noticed in early childhood. Gershon has discovered that the same genes involved in synapse formation between neurons in the brain are involved in the alimentary synapse formation. 'If these genes are affected in autism,' he says, 'it could explain why so many kids with autism have GI motor abnormalities' in addition to elevated levels of gut-produced serotonin in their blood.

Down the road, the blossoming field of neurogastroenterology will likely offer some new insight into the workings of the second brain—and its impact on the body and mind. 'We have never systematically looked at [the enteric nervous system] in relating lesions in it to diseases like they have for the' central nervous system, Gershon says. One day, perhaps there will be well-known connections between diseases and lesions in the gut's nervous system as some in the brain and spinal cord today indicate multiple sclerosis.

Cutting-edge research is currently investigating how the second brain mediates the body's immune response; after all, at least 70 percent of our immune system is aimed at the gut to expel and kill foreign invaders.

U.C.L.A.'s Mayer is doing work on how the trillions of bacteria in the gut 'communicate' with enteric nervous system cells (which they greatly outnumber). His work with the gut's nervous system has led him to think that in coming years psychiatry will need to expand to treat the second brain in addition to the one atop the shoulders."

Image Credit: http://fitlife.tv/wp-content/uploads/2015/06/Gut-System.bmp






According to John's Hopkins http://www.hopkinsmedicine.org/health/healthy_aging/healthy_body/the-brain-gut-connection,

"If you’ve ever "gone with your gut' to make a decision or felt 'butterflies in your stomach' when nervous, you’re likely getting signals from an unexpected source: your second brain. Hidden in the walls of the digestive system, this 'brain in your gut' is revolutionizing medicine’s understanding of the links between digestion, mood, health and even the way you think.

Scientists call this little brain the enteric nervous system (ENS). And it’s not so little. The ENS is two thin layers of more than 100 million nerve cells lining your gastrointestinal tract from esophagus to rectum.



What Does Your Gut’s Brain Control?

Unlike the big brain in your skull, the ENS can’t balance your checkbook or compose a love note. 'Its main role is controlling digestion, from swallowing to the release of enzymes that break down food to the control of blood flow that helps with nutrient absorption to elimination,' explains Jay Pasricha, M.D., director of the Johns Hopkins Center for Neurogastroenterology, whose research on the enteric nervous system has garnered international attention. 'The enteric nervous system doesn’t seem capable of thought as we know it, but it communicates back and forth with our big brain—with profound results.'

The ENS may trigger big emotional shifts experienced by people coping with irritable bowel syndrome (IBS) and functional bowel problems such as constipation, diarrhea, bloating, pain and stomach upset. 'For decades, researchers and doctors thought that anxiety and depression contributed to these problems. But our studies and others show that it may also be the other way around,' Pasricha says. Researchers are finding evidence that irritation in the gastrointestinal system may send signals to the central nervous system (CNS) that trigger mood changes.

'These new findings may explain why a higher-than-normal percentage of people with IBS and functional bowel problems develop depression and anxiety,' Pasricha says. 'That’s important, because up to 30 to 40 percent of the population has functional bowel problems at some point.'



New Gut Understanding Equals New Treatment Opportunities

This new understanding of the ENS-CNS connection helps explain the effectiveness of IBS and bowel-disorder treatments such as antidepressants and mind-body therapies like cognitive behavioral therapy (CBT) and medical hypnotherapy. 'Our two brains ‘talk’ to each other, so therapies that help one may help the other,' Pasricha says. 'In a way, gastroenterologists (doctors who specialize in digestive conditions) are like counselors looking for ways to soothe the second brain.'

Gastroenterologists may prescribe certain antidepressants for IBS, for example—not because they think the problem is all in a patient’s head, but because these medications calm symptoms in some cases by acting on nerve cells in the gut, Pasricha explains. 'Psychological interventions like CBT may also help to 'improve communications' between the big brain and the brain in our gut,' he says.



Still More to Learn About Mind-Gut Link

Pasricha says research suggests that digestive-system activity may affect cognition (thinking skills and memory), too. 'This is an area that needs more research, something we hope to do here at Johns Hopkins,' he says.

Another area of interest: Discovering how signals from the digestive system affect metabolism, raising or reducing risk for health conditions like type 2 diabetes. 'This involves interactions between nerve signals, gut hormones and microbiota—the bacteria that live in the digestive system,'Pasricha says."

Image Credit: https://www.lotronex.com/Images/Patient-MOA_1.jpg




According to Neurology Advisor,

"Recently, evidence has accumulated to support a complex neurobiologic basis for migraine, with origins beyond the brain. The prevailing theory involves the gut-brain axis, which postulates a complex interplay between the brain and the gastrointestinal tract. However, the precise mechanism that links the brain and the gut and triggers a migraine event remains unclear."

Read more about it here: http://www.neurologyadvisor.com/migraine-and-headache/what-we-know-association-between-migraine-gastrointestinal-health/article/695858/

Image Source: The Smithsonian.









According to The Smithsonian,

"The human microbiome—a collection of bacteria, archaea, fungi and viruses commingling in the gut and intestines—has been linked to a wide range of human health conditions, including digestive health and the prevention of autoimmune diseases. Some research has even identified a possible link between gut health and brain function. Building on this work, a study published yesterday in Nature Microbiology reveals that clinical depression could be affected by the amounts of certain bacteria in the gut.

The research team, led by microbiologist Jeroen Raes of the Catholic University of Leuven in Belgium, found that almost all gut bacteria are able to produce neurotransmitters, which are chemicals like dopamine and serotonin that enable communication between neurons. If these 'chemical messengers' are sent to receptors in the brain, they can influence mood and behavior. The researchers also identified two strains of bacteria that are lacking in the guts of people who have been diagnosed with depression.

The study adds to mounting evidence that an association between gut health and the brain exists. However, it does not establish whether poor mental health causes depletion of the bacteria, or if the missing bacteria intensifies symptoms associated with mood disorders. More research is needed to conclusively say that gut bacteria influences mental health, says Mark Lyte, a professor of microbiology at Iowa State University who wasn’t involved in the study.

'The studies are just really starting,' Lyte says. 'We do not fully understand what all the genes in all the bacteria do, so don't make the conclusion that we understand everything about the microbiota in terms of their genetic capacity to make [neurotransmitters]. We only understand a fraction of that.' Scientists recently identified more than 100 new species of bacteria in the human gut, underscoring how much we still have to learn about the functions of the microbiome.

Raes and his team studied the gut bacteria of over 2,000 European participants to examine a possible link between the microbiome and mental health. In their study, the team tested the genomes of 532 strains of bacteria to determine if the bacteria could create neurotransmitters. Over 90 percent of the bacteria in the study demonstrated the ability to produce one or more of these chemical messengers.

The body’s longest nerve, the vagus nerve, runs from the brainstem to the lowest part of the intestines. The nerve is thought to be a two-way highway, sending signals from the brain to the gut to regulate digestion and bringing signals from the gut to the brain. The latter function provides a possible pathway for neurotransmitters produced by gut bacteria to influence mental health, Raes says. The team found that both Coprococcus and Dialister bacteria were depleted among individuals with depression, even when controlling for the effects of antidepressants. Coprococcus was also found to have a biological pathway associated with dopamine, a neurotransmitter known to influence mental health.

The next step, Lyte says, is to develop a more complete understanding of how these two strains of bacteria function in the gut. Scientists have studied the genetic traits of some bacteria extensively, like E. Coli, but the genomes and traits of bacteria like Coprococcus and Dialister have yet to be carefully examined. Lyte says that scientists will need to use 'old-school' microbiology, growing these bugs in petri dishes to see how they function. A bacterium that behaves one way on paper could function very differently when exposed to a diverse environment of microbes similar to the human gut.

'You have to grow these bugs up and see what they do [in different environments] to understand what they’re going to do when they’re in the host,' Lyte says.

Additionally, Raes says his team has only identified bacteria that could influence mental health at the genus level, and that it’s crucial to identify the specific species of bacteria that are absent in people with depression to test a possible relationship between the gut and the brain. While lower levels of Dialister were associated with depression, a recent paper linked higher levels of Dialister with arthritis. It could be that prevalence of one species of Dialister increases risk of arthritis while prevalence of another reduces risk of depression, Raes says, but determining such specifics will require additional studies.

The ability to produce neurotransmitters also might be unique to bacteria that evolved in the gut, as the capability hasn’t been found in wild bacteria outside the microbiome. 'It feels like an evolutionary adaptation to the symbiosis of bacteria and [humans],' Raes says. 'If you start thinking about that, then your head explodes. Bacteria live within us and have found all these ways to communicate with us and potentially influence our behavior.'

Emma Allen-Vercoe, a professor of microbiology at the University of Guelph in Ontario, says she is excited about the future potential of microbiome research. While many more studies would be required before scientists could perform a treatment trial, Allen-Vercoe believes that Coprococcus and Dialister could be great candidates to use as psychobiotics, or probiotics that target mental health. Finding a way to grow these microbes so they could be administered to patients would be 'far from trivial,' but she hopes scientists can eventually introduce the bacteria into human guts of and examine the results.

'When I read this paper I was super excited, because I really think this is a new frontier in medicine,' Allen-Vercoe says. 'Thinking outside the box in terms of using microbes in the gut to treat diseases that traditionally haven’t been associated with the gut is quite exciting, because we’re thinking about things in a whole different way. They’ve really started something here.'"

Thank you, to one of our group members, Sarah L., for bringing the article above to my attention! I really appreciate it!



So, the brain in your gut can affect your memory. It makes me think that if you have little or no motility, it could contribute to memory loss, in addition to other things like sleep deprivation, malnutrition, and medication. It seems like a lot of issues can cause memory loss in those who suffer from Gastroparesis/DTP. Personally, I have to carry around a journal to write things in because I forget a lot of things. More research is going into this, so hopefully, we will have answers soon.

Losing A Loved One To a Chronic Illness and Handling Grief

We have all been there. We see a post or get a call, and the floor drops out from under us. We don't know what to do or what to say because we have just been told that one of our loved ones has passed away, without rhyme or reason, due to complications from a chronic illness. How do you handle that? It seems like it goes beyond the regular grieving process because you watched this person suffer and wrestle with a chronic illness for a long time before they passed. You get angry because people make off hand comments that they knew this person was going to die because they were so ill, yet the last time you talked to your loved one, they were fine. So, how do you deal with the news, knowing that you will never get to have another conversation? Knowing what you do about their illness?

With Gastroparesis, it can be a lot more sneaky. I mean, most people seem fine on the outside but are suffering immensely behind the scenes. If you want to know more about how people with Gastroparesis live and what they suffer from, I have great resources in my blog. But this article, this is to honor those fallen GP Warriors, those who have given their lives to fight for a cure for Gastroparesis. We will never forget them and we will keep them alive in our hearts and our memories, and keep them alive in our fight. So, again, how do you deal with the loss? Based on my personal experiences, I'm going to share some things that really help me when I lose a loved one, especially really good friends, to an invisible illness.

I have another article with the stages of grief in it, entitled, "The Grieving Process for a Chronic Illness, and How to Overcome It" that you can find by clicking here: http://www.emilysstomach.com/2014/02/the-grieving-process-for-chronic.html. This will tell you about the stages of grief. I recommend reading it so that you can prepare yourself and to know how grief effects people.

The only logical answer I can give you is that there is no way to get over a loss. You can move past it, but you never truly get over losing a loved one, especially to a chronic illness.

Lean on support groups, with other people who have gone what you are going through, to help you through this difficult time. I recommend that highly, because people are social animals, and it helps to have empathy and people on your side with what you're going through. I started a Facebook Group, Grief Group for GPers, for those who have lost loved ones to Gastroparesis and who want to talk about it. We ask that everything posted in the group, stays in the group, due to family privacy matters. We also have an album of loved ones who have passed that we keep updated, so that we never forget why we are fighting and who we are fighting for, when we fight for things like awareness, research, and a cure for Gastroparesis. The group can be found here: http://www.facebook.com/groups/gpgriefgroup/.

Joining a support group can definitely help, but I also recommend writing. Writing helps me a lot. When I'm able to get out all of my feelings onto a laptop or a piece of paper, I feel purged and a lot better. You can tear up the paper afterwards or delete a word document, if you don't want anyone else to stumble across it but it helps to get your feelings out. I write this blog to help me deal with even having an invisible illness and most days, it helps me keep my sanity. You don't have to start a blog, but keeping a notebook will help. Like I said, you don't have to keep your feelings once you've written them down. You can throw them away, tear them up, do whatever you like to the page(s) that you write. I like to keep mine to reflect back on how I was feeling and how far I've come since that point. I have a journal that I write in and carry around with me, in addition to this blog.

Lean on your friends. I know this seems like a no-brainer, but your friends are there to support you and help you. Invite them over to your house (I don't know about you, but it's hard for me to go out since I suffer from nausea and vomiting a lot due to GP, gastroparesis, but everyone's GP is different) and put on a movie that you all love, play a game, board or video, and talk. It helps having a distraction and your friends will be there for you. You can tell them about your loved one, relive memories, and honor them in your own way. It helps, at times like these, to have friends you can depend on to make you feel better and the interaction will really help, especially if you've been keeping yourself in isolation.

And the last thing that I would recommend, especially if you can't go to the funeral, is to have your own ceremony. I know this sounds weird, but hear me out. You can do something simple and personal, between you and the loved one you lost. I take flowers, they can be hand picked or bought at a store, and I sit in the backyard. I place them at the edge of the yard, and I talk to my loved one that I've lost. I tell them how I feel, and you can do this in your head if you want to, especially if there are people outside. The important thing is to let out any pent up tears and feelings. Talk to the person you lost like they were there with you, next to you. Lay down the flowers and have your own moment. You don't need a funeral to let them know how you feel. I know I have a hard time going places because I vomit quite a lot, and I am always nauseated. Being in a car exacerbates that feeling, because I get motion sick, so I have my own ceremony, in my backyard. I know this sounds odd, but it really helps me. It helps me say goodbye and saying goodbye, in your own way, is very important. It's important that you let go. You can do whatever makes you feel comfortable, this is just my own little ritual I want to share with you to give you an idea of the things you can do. This is just very personal for me, and this is something I've never told anyone. A good friend of mine, whom I lost, once told me that she didn't want to die because of the suffering she would cause to the people left behind. I still think about that and she's been gone for twenty years.

We have lost five people so far, just this month, from complications due to Gastroparesis. It breaks my heart and saddens me...but it also gives me purpose. I want to continue fighting for those people whom we've lost, and I want to do it to keep them alive. One day, we will find a cure. But, for right now, I have high hopes for more awareness and research. I actually met a lady at the dentist who knew all about Gastroparesis, and I didn't have to explain it to her. She had read about it somewhere. It's going to happen. It may be slow, but awareness is taking shape, and hopefully, research and a cure aren't far behind it.

May our loved ones walk among the stars and be proud of us for carrying on and fighting for Gastroparesis.

My friend shared this article with me and I wanted to post it here, because it is amazing and I think it would help with the grief.

According to Funnyshare.com (http://beautythings.info/2017/09/24/when-asked-for-advice-on-how-to-deal-with-grief-this-old-man-gave-the-most-incredible-reply/),

"When Asked for Advice on How to Deal with Grief, This Old Man Gave the Most Incredible Reply.

Someone on reddit wrote the following heartfelt plea online:

'My friend just died. I don’t know what to do.'

Many people responded with words of encouragement, but one response in particular, by an older gentlemen, really stood out from the rest…

Alright, here goes. I’m old. What that means is that I’ve survived (so far) and a lot of people I’ve known and loved did not. I’ve lost friends, best friends, acquaintances, co-workers, grandparents, mom, relatives, teachers, mentors, students, neighbors, and a host of other folks. I have no children, and I can’t imagine the pain it must be to lose a child. But here’s my two cents.

I wish I could say you get used to people dying. I never did. I don’t want to. It tears a hole through me whenever somebody I love dies, no matter the circumstances. But I don’t want it to 'not matter.' I don’t want it to be something that just passes. My scars are a testament to the love and the relationship that I had for and with that person. And if the scar is deep, so was the love.

So be it. Scars are a testament to life. Scars are a testament that I can love deeply and live deeply and be cut, or even gouged, and that I can heal and continue to live and continue to love. And the scar tissue is stronger than the original flesh ever was. Scars are a testament to life. Scars are only ugly to people who can’t see.

As for grief, you’ll find it comes in waves. When the ship is first wrecked, you’re drowning, with wreckage all around you. Everything floating around you reminds you of the beauty and the magnificence of the ship that was, and is no more. And all you can do is float. You find some piece of the wreckage and you hang on for a while. Maybe it’s some physical thing. Maybe it’s a happy memory or a photograph. Maybe it’s a person who is also floating. For a while, all you can do is float. Stay alive.

In the beginning, the waves are 100 feet tall and crash over you without mercy. They come 10 seconds apart and don’t even give you time to catch your breath. All you can do is hang on and float. After a while, maybe weeks, maybe months, you’ll find the waves are still 100 feet tall, but they come further apart. When they come, they still crash all over you and wipe you out.

But in between, you can breathe, you can function. You never know what’s going to trigger the grief. It might be a song, a picture, a street intersection, the smell of a cup of coffee. It can be just about anything…and the wave comes crashing. But in between waves, there is life.

Somewhere down the line, and it’s different for everybody, you find that the waves are only 80 feet tall. Or 50 feet tall. And while they still come, they come further apart. You can see them coming. An anniversary, a birthday, or Christmas, or landing at O’Hare. You can see it coming, for the most part, and prepare yourself. And when it washes over you, you know that somehow you will, again, come out the other side. Soaking wet, sputtering, still hanging on to some tiny piece of the wreckage, but you’ll come out.

Take it from an old guy. The waves never stop coming, and somehow you don’t really want them to. But you learn that you’ll survive them. And other waves will come. And you’ll survive them too. If you’re lucky, you’ll have lots of scars from lots of loves. And lots of shipwrecks."

I do not have the source for this, but it does help me in times of grief:

Image Source: taken from Imgur

According to www.Churchill.com,

"Introduction - As much as we don’t like to think about it, death is a part of life. While it’s not a nice thought, there’s nothing we can do to stop those we love from passing away when the time comes. It’s understandable to feel sad and even helpless when this happens, but the pain will become easier to cope with over time.

Common feelings after a death

People go through various stages of grief when they’re coming to terms with a death. These five stages have been studied for years:

1. Denial. By denying the death has happened, it prevents the person from being overwhelmed by grief. It’s normal to feel numb, wondering how life can go on. It can be hard to accept what’s happened.

1. Anger. Being easily irritated is a normal response to the loss of someone close to you. You might feel like snapping at people, even if it’s unlike you.

1. Bargaining. While we feel helpless, it’s natural for thoughts to turn to what could’ve been done differently. For example, being nicer to the person or getting medical help earlier.

1. Depression. When our thoughts return to the present, it often leads to another level of sadness. At this point, it’s normal for a person to struggle most with the loss.

1. Acceptance. You’re not okay with what’s happened, but you’ve reached a point where you can get on with your life without it having too much of an impact day-to-day.

Understanding the common stages of grief can help a person be better prepared, but everyone grieves differently. There’s no right or wrong amount of time to be upset about losing someone, so let things progress naturally.

The biological process of grief 

Your body responds when you’re grieving. Once grief has triggered a response, you’re likely to experience a number of side effects, including:

• Boosted adrenaline. Our brain triggers the fight or flight response, leading to a faster heartbeat and additional release of adrenaline. You might feel on high alert.

• Exhaustion. Often caused by a lack of sleep, grief can lead to insomnia and depression – leaving you drained of energy and motivation.

• Digestion problems. Issues with your digestion can be common when experiencing sadness.

If you lose someone close to you, be prepared for short-term changes to your health. It’s normal to feel the effects on your body. Staying active and eating well can help.

Daily life when you’re grieving 

How to maintain your regular lifestyle
The impact a death will have on your life is significant. But there are ways to cope with a loss, including:

• Create a routine. Having a routine in place can help keep you balanced. A structure will give you a solid foundation to rebuild from, at a time when you’re struggling to find your feet.

• Talk to loved ones. Open up to the people closest to you. You’ll be sharing a lot of the same feelings and talking about them is an important part of grieving.

• Encourage yourself to participate. It’s natural to withdraw from life when you’re under stress. If you find yourself feeling this way, take small steps to do the things that usually make you happy.

Helping children cope with a death 

The loss of a loved one can be especially hard on children, because it’s probably the first time they’ve experienced these feelings. You’ll play a large part in helping them deal with their grief.

• Use clear and honest words. Be as clear as possible when speaking to a child. They’re probably struggling to understand what’s happening, so being open will help them process what’s going on.

• Listen to their concerns and questions. Make sure you answer any questions they have, and let the child know it’s perfectly normal to feel the way they do.

• Explain funerals. There’s a good chance a child won’t know what a funeral is. If you want them to go, give them a description of why it happens, and what to expect on the day.

• Help them remember the person. Talking about memories of a lost loved one can be helpful to children. This positive energy is therapeutic and may help them battle through the worst of what they’re experiencing.

• Do things to keep their minds active. Keep a child happy and distracted with activities such as family days out. Sitting inside for too long won’t help anyone.

Helping adults around you to grieve 

It’s not only children who grieve. You might want to help a partner, friend or family member who’s experiencing this kind of pain. Some of the best methods include:

• Listening to them. Don’t presume the grieving person would want to be treated the same way you would. Just having someone to listen to them can help. You don’t always have to give advice or have a solution.

• Talk about the person who’s passed. Sometimes people feel as though mentioning the deceased will be upsetting. But somebody who’s grieving might want to talk about their loved one, so give them time to bring it up.

• Reaching out. Don’t wait for someone to ask you for help. While you don’t want to be pushy, it’s nice to make sure a person knows you’re there if needed.

• Point them towards professional help. If they’re struggling to come to terms with their loss, you can suggest they seek professional help.

Getting help with grief 

Finding the support and care you need at this distressing time can make a huge difference. 

Getting emotional support from those around you 

During difficult times, we rely on those closest to us for support. But we’ve got to want their help, so bear in mind these points:

• Share your issues. Make sure people around you know if you’re struggling. There’s a better chance they’ll be able to help if they know what’s up.

• Say yes to help. If someone reaches out to offer you advice, be open to their support. A heart-to-heart can make a difference. It’s worth getting a range of support too, from friends and professionals.

It can be uncomfortable to open up about your issues, but it’s important to separate yourself from those doubts to get the help you need.

Taking steps to help with your own emotional health 

Looking after your emotional health and well-being is always important, especially when you’re suffering a loss.

• Stay physically active. Exercising has been shown to have a positive impact on not only your body, but also your mind. Depression and anxiety can improve when you’re active.

• Take up a hobby. Take your mind off what’s troubling you by enjoying a hobby of your choice. It’s important to do things you enjoy, and not feel guilty about having a good time.

• Get enough sleep. A lack of sleep can make things worse. Try to start relaxing before it’s time to go to bed

Support lines and communities 

If you find yourself struggling, and feel like you can’t turn to anyone, there are support helplines to guide you. 

You’ll be speaking to trained professionals, with experience of helping people who are grieving. Just some of the incredible services available include:

• SupportLine. Provides phone counselling to help people with a wide variety of problems, including bereavement.

• Bereavement Trust. Focused around helping those who are experiencing grief. A team of volunteers work round the clock to make sure people can get the help and support they need.

• NHS. If you’re ever feeling dangerously low, the NHS offers a suicide hotline. Always get the support you need.

Whether it’s from your friends, family or these dedicated services, there’s always support available to you after a death. Try not to isolate yourself – instead, reach out and get help. 

If you feel like you want to talk to people who are in a similar situation to you, support groups can be a great help too. Having someone to chat to, who can relate to your situation, is incredibly useful. 

Useful links
https://www.cruse.org.uk/children/how-to-helphttps://www.helpguide.org/articles/grief/coping-with-grief-and-loss.htmhttps://www.mariecurie.org.uk/help/support/bereaved-family-friendshttps://www.nhs.uk/conditions/stress-anxiety-depression/mental-health-helplines/http://www.parentcompanion.org/article/understanding-the-stages-of-grief"

A friend sent me some websites that might help you in your grief and how to handle it with children, and the estate of a loved one:

http://www.lclark.edu/live/files/5969-grief-at-worka-guide-for-employees-and-managers

https://www.petcoach.co/article/grief-the-loss-of-a-pet/

http://www.drugrehab.org/coping-stigma-grieving-overdose-death/

https://www.vitas.com/resources/grief-and-bereavement/helping-grieving-children

https://www.cancer.org/treatment/end-of-life-care/grief-and-loss/depression-and-complicated-grief.html

https://www.neptunesociety.com/resources/preparing-for-the-death-of-a-terminally-ill-loved-one

https://www.homeadvisor.com/r/create-peaceful-at-home-hospice/

https://privatebank.wf.com/conversations/article/settling_a_family_estate

https://www.nytimes.com/2012/09/20/garden/letting-children-share-in-grief.html

https://www.parents.com/toddlers-preschoolers/development/social/talking-to-kids-about-death/

https://www.redfin.com/blog/how-to-be-estate-executor