Performance of 13C Mannitol for in Vivo Measurement of Small Intestinal Permeability

Phase 1

Completed

• Conditions: Impaired Small Intestinal Permeability
• Interventions: Dietary Supplement: 12C mannitol; Drug: Indomethacin; Dietary Supplement: 13C mannitol; Dietary Supplement: Lactulose

• Registration Number: NCT02603822
• Lead Sponsor: Mayo Clinic

Brief Summary

The investigators' overall objective with this study is to determine performance characteristics of small intestine permeability measurement using 13C mannitol and 12C (regular) mannitol.

Detailed Description

An impaired intestinal permeability is implicated in the pathophysiology of a number of disorders such as celiac disease, environmental enteropathy, inflammatory bowel disease, obesity, and HIV. Current measurements of intestinal permeability rely on urinary excretion of naturally available, orally ingested, non-absorbable sugars (e.g. lactulose, mannitol). However, dietary intake of these sugars limits interpretation from these assays.

Subjects will have an esophagogastroduodenoscopy (EGD) with biopsies and provide a baseline urine sample. They will be asked to ingest 3 saccharides (12C mannitol 100 mg,13C mannitol 100 mg and lactulose 1 g) in 250 ml of water. Urine samples will be obtained every 30 min. in the Clinical Research and Trials Unit (CRTU) for 0-2 hours. Subjects will collect 2-8 hour sample in provided container. Another container will be provided to collect the 8-24 hour urine which will be returned the following morning. Subjects will undergo an Indomethacin challenge intervention. They will be instructed to take three 25 mg capsules 8 hours before their next visit (just before fasting). They will take 3 additional 25 mg capsules 30 min. before the repeat in vivo permeability testing. Repeat EGD with duodenal biopsies will be done. Long term follow-up will be done within 4-6 weeks of previous testing, where subjects will once again be asked to complete the in vivo permeability testing.

Study Timeline

• Study Start: 2015-08
• Study First Submitted: 2015-09-22
• Study First Submitted QC: 2015-11-10
• Study First Posted: 2015-11-13
• Primary Completion: 2018-07-17
• Study Completion: 2018-07-17
• Status Verified: 2019-06
• Last Update Submitted: 2019-06-03
• Last Update Posted: 2019-06-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Healthy Volunteers	12C mannitol	Subjects will receive a saccharide solution of 12C mannitol 100 mg, 13C mannitol 100 mg, and lactulose 1 g in 250ml of water at visits 2, 5, and 7 prior to permeability testing. The subjects will also receive Indomethacin capsules prior to visit 5.
Healthy Volunteers	Lactulose	Subjects will receive a saccharide solution of 12C mannitol 100 mg, 13C mannitol 100 mg, and lactulose 1 g in 250ml of water at visits 2, 5, and 7 prior to permeability testing. The subjects will also receive Indomethacin capsules prior to visit 5.
Healthy Volunteers	13C mannitol	Subjects will receive a saccharide solution of 12C mannitol 100 mg, 13C mannitol 100 mg, and lactulose 1 g in 250ml of water at visits 2, 5, and 7 prior to permeability testing. The subjects will also receive Indomethacin capsules prior to visit 5.
Healthy Volunteers	Indomethacin	Subjects will receive a saccharide solution of 12C mannitol 100 mg, 13C mannitol 100 mg, and lactulose 1 g in 250ml of water at visits 2, 5, and 7 prior to permeability testing. The subjects will also receive Indomethacin capsules prior to visit 5.

Primary Outcome Measures

Name	Time	Method
Small intestine permeability as measured by change in cumulative excretion of mannitol 0-2 hours	baseline, approximately 2 hours

Secondary Outcome Measures

Name	Time	Method
Colonic permeability as measured by change in mannitol excretion between 8 and 24 hours	8 hours, approximately 24 hours
Change in hour lactulose-mannitol excretion assay between 8 and 24 hours	8 hours, approximately 24 hours	The ratio of urinary excretion of lactulose to mannitol was used to measure intestinal mucosal permeability, with higher ratios indicative of increased intestinal permeability.
Change in mannitol excretion at 24 hours	baseline, approximately 24 hours
Change in lactulose-mannitol excretion assay at 2 hours	baseline, approximately 2 hours	The ratio of urinary excretion of lactulose to mannitol was used to measure intestinal mucosal permeability, with higher ratios indicative of increased intestinal permeability.

Trial Locations

Locations (1)

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