Diarrhea-Predominant Irritable Bowel Syndrome
Conditions
Keywords
Irritable Bowel Syndrome, Glutamine, Intestinal Permeability
Brief summary
New and effective treatments are needed for patients with post-infectious irritable bowel syndrome (PI-IBS). We conducted a randomized, placebo-controlled trial to assess the efficacy and safety of glutamine, an abundant amino acid in the body and the principal fuel for enterocytes, in patients who developed diarrhea-predominant irritable bowel syndrome with increased intestinal permeability following an enteric infection.
Detailed description
In a double-blind trial, eligible adults with post-infectious IBS with increased intestinal permeability were randomly assigned to receive either glutamine (5 g three times daily) or placebo for eight weeks. The primary end point was the proportion of patients who had a reduction of ≥50 on the Irritable Bowel Severity Scoring System (IBS-SS).
Interventions
DRUGGlutamine
Drug
Sponsors
Tulane University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 72 Years
Healthy volunteers
No
Inclusion criteria
* men and women age 18-72 years old who developed post-infectious diarrhea-predominant IBS (D-IBS) * increased intestinal permeability on Lactulose/Mannitol permeability test * able and willing to cooperate with the study * \*absence of alcohol or NSAIDs 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 * Abnormal blood urea nitrogen(BUN) and/or creatinine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Irritable Bowel Symptom Severity Scale | baseline and 8 weeks following therapy | The primary outcome measure will be a change in the Irritable Bowel Symptom Severity Scale (IBS-SS) from baseline to 8 weeks at the conclusion of therapy. The IBS-SS scale ranges from 0 to 500 (worst). A decrease in 50 or greater in the IBS-SS is considered a positive response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Intestinal Permeability | baseline and 8 weeks following therapy | The secondary outcome measure will be a change in intestinal permeability from baseline to 8 weeks at the conclusion of therapy. Intestinal permeability is measured by the urinary lactulose/mannitol ratio following ingestion of a solution of lactulose and mannitol. |
| Stool Frequency | Baseline and 8 weeks following therapy | Baseline and 8 week at the conclusion of therapy |
| Stool Consistency | Baseline and 8 weeks following therapy | Bristol Stool Scale The Bristol Stool Scale characterizes stool characteristics and ranges from a minimum score of 1 with depicts hard or constipated stool to a maximum score of 7 which is watery or diarrheal stools. In this trial, stool that is less than 7 is better and depicts a good outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Glutamine Oral Glutamine Powder | 54 |
| Placebo Oral Whey Protein Powder | 52 |
| Total | 106 |
Baseline characteristics
| Characteristic | Glutamine | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 32.4 years STANDARD_DEVIATION 9.5 | 30.9 years STANDARD_DEVIATION 7.1 | 31.7 years STANDARD_DEVIATION 8.3 |
| Region of Enrollment United States | 54 Participants | 52 Participants | 106 Participants |
| Sex: Female, Male Female | 37 Participants | 37 Participants | 74 Participants |
| Sex: Female, Male Male | 17 Participants | 15 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 54 | 0 / 52 |
| other Total, other adverse events | 0 / 54 | 0 / 52 |
| serious Total, serious adverse events | 0 / 54 | 0 / 52 |
Outcome results
Primary
Change in the Irritable Bowel Symptom Severity Scale
The primary outcome measure will be a change in the Irritable Bowel Symptom Severity Scale (IBS-SS) from baseline to 8 weeks at the conclusion of therapy. The IBS-SS scale ranges from 0 to 500 (worst). A decrease in 50 or greater in the IBS-SS is considered a positive response.
Time frame: baseline and 8 weeks following therapy
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glutamine | Change in the Irritable Bowel Symptom Severity Scale | 181 units on a scale | Standard Deviation 48 |
| Placebo | Change in the Irritable Bowel Symptom Severity Scale | 301 units on a scale | Standard Deviation 57 |
Secondary
Intestinal Permeability
The secondary outcome measure will be a change in intestinal permeability from baseline to 8 weeks at the conclusion of therapy. Intestinal permeability is measured by the urinary lactulose/mannitol ratio following ingestion of a solution of lactulose and mannitol.
Time frame: baseline and 8 weeks following therapy
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glutamine | Intestinal Permeability | 0.05 lactulose/mannitol (L/M) | Standard Deviation 0.01 |
| Placebo | Intestinal Permeability | 0.10 lactulose/mannitol (L/M) | Standard Deviation 0.03 |
Secondary
Stool Consistency
Bristol Stool Scale The Bristol Stool Scale characterizes stool characteristics and ranges from a minimum score of 1 with depicts hard or constipated stool to a maximum score of 7 which is watery or diarrheal stools. In this trial, stool that is less than 7 is better and depicts a good outcome.
Time frame: Baseline and 8 weeks following therapy
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glutamine | Stool Consistency | 3.9 units on a scale (1-7) | Standard Deviation 1.2 |
| Placebo | Stool Consistency | 6.6 units on a scale (1-7) | Standard Deviation 0.53 |
Secondary
Stool Frequency
Baseline and 8 week at the conclusion of therapy
Time frame: Baseline and 8 weeks following therapy
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glutamine | Stool Frequency | 2.9 stools per day | Standard Deviation 0.9 |
| Placebo | Stool Frequency | 5.3 stools per day | Standard Deviation 2.1 |