Diarrhea, Diarrhea Predominant Irritable Bowel Syndrome
Conditions
Keywords
Gluten, Diarrhea or diarrhea predominant irritable bowel syndrome, Colonic permeability, Small bowel permeability, Colonic inflammatory response, Small bowel inflammatory response
Brief summary
The specific hypotheses are: Gluten supplementation for four weeks increases small intestinal permeability and accelerates colonic transit in patients with irritable bowel syndrome with diarrhea (IBS-D) or functional diarrhea (FD) who are HLA-DQ2 positive.
Detailed description
The study design is a double-blind, randomized, controlled, parallel-group, 6-week study comparing the effects of gluten rich versus gluten free diets in diarrhea or diarrhea predominant IBS patients. All participants will keep a daily bowel pattern diary throughout the study. All participants will have negative serum tissue transglutaminase (TTg) assay, and anti-endomysial antibody test, if TTg is positive or equivocal. All participants will have the following studies performed both before and after the 4-week dietary intervention: 1. Stool samples to check markers of inflammation such as fecal calprotectin. 2. Blood samples to check markers of inflammation and for genetic testing. 3. After ingestion of the mannitol, lactulose and sucralose sugars, urine samples to indirectly measure small intestinal and colonic permeability. 4. After sedation, upper gastrointestinal endoscopy and flexible sigmoidoscopy to obtain 6 mucosal biopsies from the small bowel and sigmoid colon for immunohistochemical analysis. 5. Scintigraphy to measure gastrointestinal transit.
Interventions
OTHERGluten free diet
A 4-week gluten free diet provided
OTHERGluten rich diet
A 4-week gluten rich diet is provided
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Diarrhea or diarrhea predominant IBS patients 2. Age 18 to 65 3. BDQ confirms presence of IBS-D or functional diarrhea, positive by Rome III criteria 4. No restrictions on Hospital Anxiety Depression score 5. No abdominal surgery (except appendectomy and cholecystectomy)
Exclusion criteria
1. Serum tissue transglutaminase IgA or IgG positive or medical record of small bowel biopsy suggestive of celiac disease 2. Use of tobacco products within the past 6 months (since nicotine may affect intestinal permeability) 3. Use of NSAIDs or aspirin within the past week (since NSAIDs affect intestinal permeability) 4. Use of oral corticosteroids within the previous 6 weeks 5. Ingestion of artificial sweeteners such as SplendaTM (sucralose), Nutrasweet TM(aspartame), lactulose or mannitol 2 days before the study begins, e.g., foods to be avoided are sugarless gums or mints and diet soda 6. Ingestion of any prescription, over the counter, or herbal medications which can affect gastrointestinal transit 7 days before study begins. 7. Any females who are pregnant or trying to become pregnant (due to radiation exposure) 8. Bleeding disorders or medications that increase risk of bleeding from mucosal
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Small bowel permeability | 0 - 2 hours post sugar ingestion | Excretion of mannitol 0-2 hours after liquid formulation |
| Colonic permeability | 2 -24 hours post sugars ingestion | Cumulative excretion of mannitol at 2-24 hours after liquid |
| Colonic transit | 24 hours | Colonic transit geometric center at 24 hours |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Gastric emptying | 0-2 hours | Gastric emptying T1/2 |
| Colonic inflammatory response | 4 weeks | Sigmoid colon mucosal immunocyte count in lamina propria |
| Colon transit | 6-12 hours | Ascending colon emptying T1/2 |
| Small bowel inflammatory response | 4 weeks | Duodenal mucosal immunocyte count in lamina propria |
| Stool frequency and consistency | 6 weeks | Bowel pattern diary |
| Colonic permeability | 2-24 hours after sugars ingestion | Cumulative excretion of lactulose |
| Small bowel transit time | 6 hours | Colonic filling at 6 hours (%) |
Countries
United States
Outcome results
None listed