Biomarkers for Intestinal Permeability in Patients With Constipation

Irritable Bowel Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02246647
• Other study ID #: 14-002382
• Status: Completed
• Start date: September 2014
• Est. completion date: December 8, 2016

Study information

• Verified date: August 2019
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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).

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: December 8, 2016
• Est. primary completion date: December 8, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Constipation
• Intestinal Diseases
• Irritable Bowel Syndrome

Intervention

Diagnostic Test:
• Permeability measurement
Saccharide excretion was compared between IBS-C and healthy volunteers

Procedure:
• Esophagogastroduodenoscopy
Duodenal biopsies were collected from IBS-C and healthy volunteers
• Flexible sigmoidoscopy
Colonic biopsies were collected from IBS-C and healthy volunteers

Locations

Country	Name	City	State
United States	Mayo Clinic in Rochester	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	Takeda Pharmaceuticals International, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Lactulose:C13 Mannitol Excretion Ratio 8-24hrs.	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.	8-24 hr post test-dose administration
Secondary	Lactose:C13 Mannitol Excretion Ratio 0-2hours		0-2 hr post-test dose administration
Secondary	Baseline Transmucosal Resistance (TMR) of Duodenal Mucosa		Baseline
Secondary	Cumulative FITC-Dextran (4kDa) Concentration Across Duodenal Mucosa	This is not a pharmacokinetic or pharmacodynamic measure. Hence only one time assessment is made 3 hours after FITC-Dextran (4kDa) administration.	3 hours post FITC-Dextran (4kDa) administration
Secondary	Rate of FITC-Dextran (4kDa) Flux Across Duodenal Mucosa	This is not a pharmacokinetic or pharmacodynamic measure. Hence only one time assessment is made 3 hours after FITC-Dextran (4kDa) administration.	Over 3 hours post FITC-Dextran (4kDa) administration
Secondary	Baseline Transmucosal Resistance (TMR) of Colonic Mucosa		Baseline
Secondary	Cumulative FITC-Dextran (4kDa) Concentration Across Colonic Mucosa		3 hours post FITC-Dextran (4kDa) administration
Secondary	Rate of FITC-Dextran (4kDa) Flux Across Colonic Mucosa		Over 3 hours post FITC-Dextran (4kDa) administration
Secondary	Cumulative E.Coli Bio- Particle K12 Concentration Across Duodenal Mucosa		3 hours post E.coli Bio- Particle administration
Secondary	Rate of E.Coli Bio- Particle K12 Flux Across Duodenal Mucosa		Over 3 hours post E.coli Bio- Particle administration
Secondary	Cumulative E.Coli Bio- Particle K12 Concentration Across Colonic Mucosa		3 hours post E.coli Bio- Particle administration
Secondary	Rate of E.Coli Bio- Particle K12 Flux Across Colonic Mucosa		Over 3 hours post E.coli Bio- Particle administration
Secondary	Duodenal Impedance		Baseline
Secondary	Mean Serum Endotoxin (Bacterial LPS) Levels		Fasting, one time measurement after 8 hours