Glutamine for the Treatment of Patients With Irritable Bowel Syndrome (AT005291)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by The University of Texas, Galveston
Sponsor:
Information provided by (Responsible Party):
The University of Texas, Galveston
ClinicalTrials.gov Identifier:
NCT01414244
First received: July 29, 2011
Last updated: July 28, 2014
Last verified: July 2014
  Purpose

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. Several recent studies have shown that diarrhea-predominant IBS (D-IBS) patients have increased intestinal permeability that may lead to chronic gastrointestinal symptoms.

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. The investigators hypothesize that oral glutamine supplementation will improve the IBS Symptom Severity Scale and restore intestinal membrane permeability in diarrhea-predominant IBS patients. The investigators propose to conduct a randomized, double-blind, placebo-controlled clinical trial studying glutamine compared to placebo 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, the investigators 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 ≥50 from the baseline score on the IBS Symptom Severity Scale. Specific Aim 2: To determine if oral glutamine supplementation will restore intestinal permeability in IBS patients. To accomplish this aim, the investigators will measure the change in the intestinal permeability following treatment with either oral glutamine supplementation or placebo.


Condition Intervention Phase
Irritable Bowel Syndrome
Dietary Supplement: Glutamine Supplementation
Dietary Supplement: Placebo
Drug: Glutamine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Randomized, Placebo-Controlled Trial of Glutamine for the Treatment of Patients With Irritable Bowel Syndrome

Resource links provided by NLM:


Further study details as provided by The University of Texas, Galveston:

Primary Outcome Measures:
  • Change in the Irritable Bowel Symptom Severity Scale [ Time Frame: baseline and at 2, 4, 6, and 8 weeks following therapy ] [ Designated as safety issue: No ]
    The primary outcome measure will be a change in the Irritable Bowel Symptom Severity Scale from baseline to 2, 4, 6, and 8 weeks following therapy.


Secondary Outcome Measures:
  • Change in Intestinal Permeability [ Time Frame: baseline and 2, 4, 6, and 8 weeks following therapy ] [ Designated as safety issue: No ]
    The secondary outcome measure will be a change in intestinal permeability from base to 2, 4, 6, and 8 weeks following therapy.


Estimated Enrollment: 100
Study Start Date: November 2010
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Glutamine supplementation
Glutamine
Dietary Supplement: Glutamine Supplementation
Oral Glutamine
Other Name: L-Glutamine
Drug: Glutamine
Placebo Comparator: Placebo
Whey protein powder
Dietary Supplement: Placebo
Oral Placebo
Other Name: sugar pill

  Hide Detailed Description

Detailed Description:

Abstract 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. Several mechanisms that may lead to IBS have been proposed including: alterations in receptors and neuropeptides, bacterial overgrowth and altered microbiota, altered intestinal transit, anxiety and depressive symptoms, and increased intestinal membrane permeability. Several recent studies have shown that diarrhea-predominant IBS (D-IBS) patients have increased intestinal permeability that may lead to chronic gastrointestinal symptoms.

Our laboratory recently evaluated diarrhea-predominant IBS patients and reported that they have increased membrane permeability. The investigators 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. 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, the investigators hypothesize that oral glutamine supplementation will improve the IBS Symptom Severity Scale and restore intestinal membrane permeability in diarrhea-predominant IBS patients. The investigators 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. The IBS Symptom Severity Scale and intestinal membrane permeability will be measured at baseline, 2, 4, 6, and at 8 weeks. The results of this study 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, the investigators 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 of ≥50 from the baseline score on the IBS Symptom Severity Scale. This constitutes a clinically significant response to treatment.

Hypothesis 1. IBS patients will have an improvement of ≥50 on the IBS Symptom Severity Scale following oral glutamine supplementation compared to placebo.

Specific Aim 2: To determine if oral glutamine supplementation will restore intestinal membrane permeability in IBS patients. To accomplish this aim, the investigators will measure the change in the intestinal membrane permeability following treatment with either oral glutamine supplementation or placebo.

Hypothesis 2a. Oral glutamine supplementation will restore intestinal membrane permeability in IBS patients compared to placebo.

Hypothesis 2b. Improvement in the IBS Symptom Severity Scale is correlated with restoration of intestinal membrane permeability following oral glutamine compared to placebo.

Layman Statement: 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.

  Eligibility

Ages Eligible for Study:   18 Years to 72 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • men and women age 18-72 years old that meet the Rome III criteria for diarrhea-predominant IBS (D-IBS) for at least 1 year prior to study
  • increased intestinal membrane permeability on Lactulose/Mannitol permeability test
  • score between 37 and 110 on the Functional Bowel Disorder Severity Index (FBDSI)
  • able and willing to cooperate with the study
  • *absence of alcohol ingestion for 2 weeks prior to inclusion into study and throughout the study duration

Exclusion Criteria:

  • current participation in another research protocol or unable to give informed consent
  • women with a positive urine pregnancy test or breastfeeding
  • history of inflammatory bowel disease, lactose intolerance, and/or celiac sprue
  • + hydrogen breath test for bacterial overgrowth
  • + antiendomysial antibody titer
  • use of nonsteroidal antinflammatory drug(NSAIDs) 2 weeks before or during the study
  • known allergy to glutamine
  • abdominal surgery except for removal of gallbladder, uterus, or appendix >6 months prior to entry into the study
  • Beck Depression Inventory score of ≥30, State Trait Anxiety Inventory ≥53.
  • Abnormal blood urea nitrogen(BUN) and/or creatinine
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01414244

Contacts
Contact: QiQi Zhou, M.D., Ph.D 614-271-7118 qiqi06@gmail.com

Locations
United States, Texas
University of Texas Medical Branch Recruiting
Galveston, Texas, United States, 77550
Contact: QiQi Zhou, M.D., Ph.D.    614-271-7118    qiqi06@gmail.com   
Sponsors and Collaborators
The University of Texas, Galveston
Investigators
Principal Investigator: QiQi Zhou University of Texas, Galveston
  More Information

No publications provided

Responsible Party: The University of Texas, Galveston
ClinicalTrials.gov Identifier: NCT01414244     History of Changes
Other Study ID Numbers: 11-271
Study First Received: July 29, 2011
Last Updated: July 28, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Irritable Bowel Syndrome
Colonic Diseases, Functional
Colonic Diseases
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on August 28, 2014