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OpenTrials
Completed

NCT Number: NCT02246647

Biomarkers for Intestinal Permeability in Patients With Constipation

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).

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Key information

Age range

18 year–65 year

Sex eligibility

Female

Study type

Observational

Primary location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

About this study

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

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

  • History of Inflammatory Bowel Disease (IBD) , microscopic colitis or celiac disease
  • Use of tobacco products within the past 6 months
  • Use of NSAIDs or aspirin within the past week
  • Use of oral corticosteroids within the previous 6 weeks
  • 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
  • Ingestion of any prescription, over the counter, or herbal medications which can affect gastrointestinal transit 7 days before study begins
  • Any treatment specifically taken for IBS, including loperamide, cholestyramine, alosetron
  • Drugs with a known pharmacological activity at 5-HT4, 5-HT2b or 5-HT3 receptors (e.g, tegaserod, ondansetron, tropisetron, granisetron, dolasetron, mirtazapine);
  • All narcotics (e.g, codeine, morphine, and propoxyphene, either alone or in combination)
  • Anti-cholinergic agents (e.g, dicyclomine, hyoscyamine, propantheline).
  • Ultram
  • 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);
  • Antimuscarinics;
  • Peppermint oil;
  • Systemic antibiotics, rifaximin, metronidazole.
  • Bleeding disorders or medications that increase risk of bleeding from mucosal biopsies.
  • Score > 8 for anxiety or depression on Hospital anxiety and depression scale.
  • Pregnancy

Treatment and study plan

Permeability measurement

Diagnostic Test

Saccharide excretion was compared between IBS-C and healthy volunteers

Other names: 12C Mannitol, 13C Mannitol, Lactulose

Esophagogastroduodenoscopy

Procedure

Duodenal biopsies were collected from IBS-C and healthy volunteers

Flexible sigmoidoscopy

Procedure

Colonic biopsies were collected from IBS-C and healthy volunteers

Primary outcomes

  1. Lactulose:C13 Mannitol Excretion Ratio 8-24hrs.

    Time frame: 8-24 hr post test-dose administration

    In vivo measurement of intestinal permeability using 13C mannitol & lactulose was used. High performance liquid chromatography-tandem mass spectrometry was used to measure concentrations calculated using the overall urine volume excreted in each interval. Concentrations of 13C adjusted for the % of 13C in 12C mannitol (4.98% of 12C mannitol excreted was subtracted from 13C mannitol values; determined by analyzing replicate samples of control urine). All lactulose or 13C mannitol concentrations 8-24hr post-ingestion were used to determine colonic permeability. Lactulose to 13C mannitol excretion ratios, as a measure of dose of saccharide administered, were calculated.

Secondary outcomes

  1. Lactose:C13 Mannitol Excretion Ratio 0-2hours

    Time frame: 0-2 hr post-test dose administration

  2. Baseline Transmucosal Resistance (TMR) of Duodenal Mucosa

    Time frame: Baseline

  3. Cumulative FITC-Dextran (4kDa) Concentration Across Duodenal Mucosa

    Time frame: 3 hours post FITC-Dextran (4kDa) administration

    This is not a pharmacokinetic or pharmacodynamic measure. Hence only one time assessment is made 3 hours after FITC-Dextran (4kDa) administration.

  4. Rate of FITC-Dextran (4kDa) Flux Across Duodenal Mucosa

    Time frame: Over 3 hours post FITC-Dextran (4kDa) administration

    This is not a pharmacokinetic or pharmacodynamic measure. Hence only one time assessment is made 3 hours after FITC-Dextran (4kDa) administration.

  5. Baseline Transmucosal Resistance (TMR) of Colonic Mucosa

    Time frame: Baseline

  6. Cumulative FITC-Dextran (4kDa) Concentration Across Colonic Mucosa

    Time frame: 3 hours post FITC-Dextran (4kDa) administration

  7. Rate of FITC-Dextran (4kDa) Flux Across Colonic Mucosa

    Time frame: Over 3 hours post FITC-Dextran (4kDa) administration

  8. Cumulative E.Coli Bio- Particle K12 Concentration Across Duodenal Mucosa

    Time frame: 3 hours post E.coli Bio- Particle administration

  9. Rate of E.Coli Bio- Particle K12 Flux Across Duodenal Mucosa

    Time frame: Over 3 hours post E.coli Bio- Particle administration

  10. Cumulative E.Coli Bio- Particle K12 Concentration Across Colonic Mucosa

    Time frame: 3 hours post E.coli Bio- Particle administration

  11. Rate of E.Coli Bio- Particle K12 Flux Across Colonic Mucosa

    Time frame: Over 3 hours post E.coli Bio- Particle administration

  12. Duodenal Impedance

    Time frame: Baseline

  13. Mean Serum Endotoxin (Bacterial LPS) Levels

    Time frame: Fasting, one time measurement after 8 hours

Sponsors and collaborators

Lead sponsor

Mayo Clinic

Other

Collaborators

  • Takeda Pharmaceuticals International, Inc.

Registry information

Official study title

Biomarkers for Intestinal Permeability in Patients With Functional Lower Gastrointestinal Disorders Associated With Constipation.

Important dates

Study start
2014
Primary completion
2016
Study completion
2016
First posted
Sep 23, 2014
Registry last updated
Aug 21, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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