Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is estimated to affect 20% of the US population. IBS patients have significantly decreased quality of life and utilize large amounts of health care resources. IBS patients suffer from chronic abdominal pain associated with diarrhea, constipation, and/or bloating (Verne &Cerda, 1997). Several recent studies have shown that diarrhea-predominant IBS (D-IBS) patients have increased intestinal permeability that may lead to chronic gastrointestinal symptoms (Dunlop et al., 2006;Spiller 2000;2007;Zhou et al., 2009b). Our laboratory recently evaluated diarrhea-predominant IBS patients and reported that they have increased membrane permeability (Zhou et al, 2009b). We now have obtained preliminary evidence that oral glutamine supplementation restores membrane permeability and improves chronic gastrointestinal symptoms in these IBS patients. Previously, it has been well established that deficiencies in glutamine may lead to increased membrane permeability and supplementation with glutamine can restore intestinal membrane permeability (Souba,1990;Klimberg &Souba, 1990;Labow &Souba, 2000). There are no published studies to date to support the use of glutamine for Irritable Bowel Syndrome. However, given our preliminary data and the mechanisms of action of glutamine on the gastrointestinal tract, research testing whether oral glutamine is an effective therapy in Irritable Bowel Syndrome is definitely needed. Based on these new findings, we hypothesize that oral glutamine supplementation will improve the IBS Symptom Severity Scale and restore intestinal membrane permeability in diarrhea-predominant IBS patients. We propose to conduct a randomized, double-blind, placebo-controlled clinical trial studying glutamine 10 g po tid compared to placebo 10 g po tid for 8 weeks in 100 diarrhea-predominant IBS patients. This will lead to the following specific aims:
Specific Aim 1 : To determine if oral glutamine supplementation will improve the IBS Symptom Severity Scale in IBS patients. To accomplish this aim, we will measure the change in the IBS Symptom Severity Scale following treatment with either oral glutamine supplementation or placebo. The primary outcome measure will be an improvement or clinically significant response to treatment of e50 from the baseline score on the IBS Symptom Severity Scale.
Specific Aim 2 : To determine if oral glutamine supplementation will restore intestinal membrane permeability in IBS patients. To accomplish this aim, we will measure the change in the intestinal membrane permeability following treatment with either oral glutamine supplementation or placebo.

Public Health Relevance

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by chronic abdominal pain associated with an alteration in bowel habits with diarrhea and/or constipation. IBS patients with diarrhea have been shown to have a "leaky gut" in which bacteria and toxins may penetrate the gut wall, termed increased membrane permeability. The current proposal will investigate oral glutamine supplementation as a treatment of symptoms and "leaky gut" in diarrhea-predominant IBS patients.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AT005291-03
Application #
8333853
Study Section
Special Emphasis Panel (ZAT1-LD (34))
Program Officer
Weber, Wendy J
Project Start
2010-09-30
Project End
2013-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
3
Fiscal Year
2012
Total Cost
$186,832
Indirect Cost
$64,611
Name
University of Texas Medical Br Galveston
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
800771149
City
Galveston
State
TX
Country
United States
Zip Code
77555
Zhou, QiQi; Verne, G Nicholas (2011) New insights into visceral hypersensitivity--clinical implications in IBS. Nat Rev Gastroenterol Hepatol 8:349-55
Zhou, QiQi; Verne, G Nicholas (2011) miRNA-based therapies for the irritable bowel syndrome. Expert Opin Biol Ther 11:991-5
Zhou, QiQi; Price, Donald D; Callam, Christopher S et al. (2011) Effects of the N-methyl-D-aspartate receptor on temporal summation of second pain (wind-up) in irritable bowel syndrome. J Pain 12:297-303