Biomarkers for Intestinal Permeability in Patients With Constipation

NCT02246647 | Completed Results FDA Drug

• 1 other identifier: 14-002382
• Study Type: observational
• Target: 39
• Locations: 1 country
• Sites: 1

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).

Conditions

Intestinal Diseases; Irritable Bowel Syndrome; Constipation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (13)

• Lactose:C13 Mannitol Excretion Ratio 0-2hours

  0-2 hr post-test dose administration

• Baseline Transmucosal Resistance (TMR) of Duodenal Mucosa

  Baseline

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

  3 hours post FITC-Dextran (4kDa) administration

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

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

• Baseline Transmucosal Resistance (TMR) of Colonic Mucosa

  Baseline

Study Arms (2)

Healthy volunteers

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

Diagnostic Test: Permeability measurement; Procedure: Esophagogastroduodenoscopy; Procedure: Flexible sigmoidoscopy

IBS-C

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

Diagnostic Test: Permeability measurement; Procedure: Esophagogastroduodenoscopy; Procedure: Flexible sigmoidoscopy

Interventions

Flexible sigmoidoscopy PROCEDURE

Colonic biopsies were collected from IBS-C and healthy volunteers

Healthy volunteers; IBS-C

Permeability measurement DIAGNOSTIC_TEST

Saccharide excretion was compared between IBS-C and healthy volunteers

Also known as: 12C Mannitol, 13C Mannitol, Lactulose

Healthy volunteers; IBS-C

Esophagogastroduodenoscopy PROCEDURE

Duodenal biopsies were collected from IBS-C and healthy volunteers

Healthy volunteers; IBS-C

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

IBS-Constipation patients and healthy volunteers

You may qualify if:

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

You may not qualify if:

• 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);

Sponsors & Collaborators

• Mayo Clinic: lead
• Takeda Pharmaceuticals International, Inc.: collaborator

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Colonic Biopsies Duodenal Biopsies Blood Urine Fecal

MeSH Terms

Conditions

Intestinal Diseases; Irritable Bowel Syndrome; Constipation

Interventions

Endoscopy, Digestive System

Condition Hierarchy (Ancestors)

Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases, Functional; Colonic Diseases; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Digestive System; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Digestive System Surgical Procedures; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures

Results Point of Contact

• Title: Madhusudan Grover, MBBS
• Organization: Mayo Clinic

Grover.Madhusudan@mayo.edu

507-253-5384

Study Officials

• Madhusudan Grover, MBBS

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 18, 2014
• First Posted: September 23, 2014
• Study Start: September 1, 2014
• Primary Completion: December 8, 2016
• Study Completion: December 8, 2016
• Last Updated: August 21, 2019
• Results First Posted: August 21, 2019

Record last verified: 2019-08

Locations

US (1)