Clinical trial NCT02246647: Biomarkers for Intestinal Permeability in Patients With Constipation
Official title: Biomarkers for Intestinal Permeability in Patients With Functional Lower Gastrointestinal Disorders Associated With Constipation.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Intestinal Diseases
Irritable Bowel Syndrome
Constipation
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: Takeda Pharmaceuticals International, Inc.
First posted: 2014-09-23
Enrollment: 39
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: IBS-Constipation patients and healthy volunteers

Brief summary: Our overall objective with this study is firstly to provide a comprehensive assessment of intestinal permeability, mucosal barrier function using existing biomarkers and secondly to explore novel biomarkers for measuring intestinal permeability in patients with constipation predominant Irritable Bowel Syndrome (IBS-C).

Detailed description: In order to determine the differences in permeability in IBS-C in comparison with healthy volunteers, the following will be determined: differences in in vivo small intestinal and colonic permeability, differences in small intestinal and colonic mucosal barrier function, differences in effects of fecal supernatants on barrier function of T84 monolayers, and differences in novel biomarkers for intestinal permeability

Eligibility criteria: Inclusion criteria:

1. 18 - 65 years old
2. IBS-C by Rome III criteria (for IBS-C participants)
3. No abdominal surgery (except appendectomy and cholecystectomy)

Exclusion criteria:

1. History of Inflammatory Bowel Disease (IBD) , microscopic colitis or celiac disease
2. Use of tobacco products within the past 6 months
3. Use of NSAIDs or aspirin within the past week
4. Use of oral corticosteroids within the previous 6 weeks
5. Ingestion of artificial sweeteners such as Splenda (sucralose), Nutrasweet (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

   1. Any treatment specifically taken for IBS, including loperamide, cholestyramine, alosetron
   2. Drugs with a known pharmacological activity at 5-HT4, 5-HT2b or 5-HT3 receptors (e.g, tegaserod, ondansetron, tropisetron, granisetron, dolasetron, mirtazapine);
   3. All narcotics (e.g, codeine, morphine, and propoxyphene, either alone or in combination)
   4. Anti-cholinergic agents (e.g, dicyclomine, hyoscyamine, propantheline).
   5. Ultram
   6. GI preparations

      * Anti-nausea agents (e.g, trimethobenzamide, promethazine, prochlorperazine, dimenhydrinate, hydroxyzine)
      * Osmotic laxative agents (e.g, lactulose, sorbitol or PEG solutions as Miralax and Glycolax)
      * Prokinetic agents (e.g, cisapride, metoclopramide, itopride, domperidone);
   7. Antimuscarinics;
   8. Peppermint oil;
   9. Systemic antibiotics, rifaximin, metronidazole.
7. Bleeding disorders or medications that increase risk of bleeding from mucosal biopsies.
8. Score \> 8 for anxiety or depression on Hospital anxiety and depression scale.
9. Pregnancy

Primary outcomes:
measure: Lactulose:C13 Mannitol Excretion Ratio 8-24hrs.
timeFrame: 8-24 hr post test-dose administration
Secondary outcomes:
measure: Lactose:C13 Mannitol Excretion Ratio 0-2hours
timeFrame: 0-2 hr post-test dose administration
measure: Baseline Transmucosal Resistance (TMR) of Duodenal Mucosa
timeFrame: Baseline
measure: Cumulative FITC-Dextran (4kDa) Concentration Across Duodenal Mucosa
timeFrame: 3 hours post FITC-Dextran (4kDa) administration
measure: Rate of FITC-Dextran (4kDa) Flux Across Duodenal Mucosa
timeFrame: Over 3 hours post FITC-Dextran (4kDa) administration
measure: Baseline Transmucosal Resistance (TMR) of Colonic Mucosa
timeFrame: Baseline
measure: Cumulative FITC-Dextran (4kDa) Concentration Across Colonic Mucosa
timeFrame: 3 hours post FITC-Dextran (4kDa) administration
measure: Rate of FITC-Dextran (4kDa) Flux Across Colonic Mucosa
timeFrame: Over 3 hours post FITC-Dextran (4kDa) administration
measure: Cumulative E.Coli Bio- Particle K12 Concentration Across Duodenal Mucosa
timeFrame: 3 hours post E.coli Bio- Particle administration
measure: Rate of E.Coli Bio- Particle K12 Flux Across Duodenal Mucosa
timeFrame: Over 3 hours post E.coli Bio- Particle administration
measure: Cumulative E.Coli Bio- Particle K12 Concentration Across Colonic Mucosa
timeFrame: 3 hours post E.coli Bio- Particle administration
measure: Rate of E.Coli Bio- Particle K12 Flux Across Colonic Mucosa
timeFrame: Over 3 hours post E.coli Bio- Particle administration
measure: Duodenal Impedance
timeFrame: Baseline
measure: Mean Serum Endotoxin (Bacterial LPS) Levels
timeFrame: Fasting, one time measurement after 8 hours
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Madhusudan Grover, MBBS
role: PRINCIPAL_INVESTIGATOR
References: