Biomarkers for Intestinal Permeability in Patients With Constipation

Completed

• Conditions: Constipation; Intestinal Diseases; Irritable Bowel Syndrome
• Interventions: Diagnostic Test: Permeability measurement; Procedure: Esophagogastroduodenoscopy; Procedure: Flexible sigmoidoscopy

• Registration Number: NCT02246647
• Lead Sponsor: Mayo Clinic

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

Study Timeline

• Study Start: 2014-09
• Study First Submitted: 2014-09-18
• Study First Submitted QC: 2014-09-18
• Study First Posted: 2014-09-23
• Primary Completion: 2016-12-08
• Study Completion: 2016-12-08
• Results First Submitted: 2017-07-31
• Status Verified: 2019-08
• Results First Submitted QC: 2019-08-19
• Last Update Submitted: 2019-08-19
• Results First Posted: 2019-08-21
• Last Update Posted: 2019-08-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 39

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Healthy volunteers	Permeability measurement	Permeability measurement: Ingestion of saccharides {mannitol (regular, 12C) 100 mg, lactulose 1 g and labelled (13C mannitol) 100 mg} in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy
Healthy volunteers	Esophagogastroduodenoscopy	Permeability measurement: Ingestion of saccharides {mannitol (regular, 12C) 100 mg, lactulose 1 g and labelled (13C mannitol) 100 mg} in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy
Healthy volunteers	Flexible sigmoidoscopy	Permeability measurement: Ingestion of saccharides {mannitol (regular, 12C) 100 mg, lactulose 1 g and labelled (13C mannitol) 100 mg} in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy
IBS-C	Permeability measurement	Permeability measurement: Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and labelled (13C mannitol) 100 mg} in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy
IBS-C	Esophagogastroduodenoscopy	Permeability measurement: Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and labelled (13C mannitol) 100 mg} in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy
IBS-C	Flexible sigmoidoscopy	Permeability measurement: Ingestion of saccharides (mannitol (regular, 12C) 100 mg, lactulose 1 g and labelled (13C mannitol) 100 mg} in 250ml of water Esophagogastroduodenoscopy Flexible sigmoidoscopy

Primary Outcome Measures

Name	Time	Method
Lactulose:C13 Mannitol Excretion Ratio 8-24hrs.	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 Outcome Measures

Name	Time	Method
Baseline Transmucosal Resistance (TMR) of Duodenal Mucosa	Baseline
Baseline Transmucosal Resistance (TMR) of Colonic Mucosa	Baseline
Duodenal Impedance	Baseline
Lactose:C13 Mannitol Excretion Ratio 0-2hours	0-2 hr post-test dose administration
Cumulative FITC-Dextran (4kDa) Concentration Across Colonic Mucosa	3 hours post FITC-Dextran (4kDa) administration
Cumulative E.Coli Bio- Particle K12 Concentration Across Colonic Mucosa	3 hours post E.coli Bio- Particle administration
Mean Serum Endotoxin (Bacterial LPS) Levels	Fasting, one time measurement after 8 hours
Cumulative FITC-Dextran (4kDa) Concentration Across Duodenal Mucosa	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.
Rate of FITC-Dextran (4kDa) Flux Across Duodenal Mucosa	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.
Rate of E.Coli Bio- Particle K12 Flux Across Duodenal Mucosa	Over 3 hours post E.coli Bio- Particle administration
Rate of FITC-Dextran (4kDa) Flux Across Colonic Mucosa	Over 3 hours post FITC-Dextran (4kDa) administration
Cumulative E.Coli Bio- Particle K12 Concentration Across Duodenal Mucosa	3 hours post E.coli Bio- Particle administration
Rate of E.Coli Bio- Particle K12 Flux Across Colonic Mucosa	Over 3 hours post E.coli Bio- Particle administration

Trial Locations

Locations (1)

Mayo Clinic in Rochester; 🇺🇸 Rochester, Minnesota, United States