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

NCT ID: NCT02603822

Last Updated: 2019-06-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-31
• Study Completion Date: 2018-07-17

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.

Conditions

Impaired Small Intestinal Permeability

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Healthy Volunteers

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.

Group Type: EXPERIMENTAL

12C mannitol

Intervention Type: DIETARY_SUPPLEMENT

12C mannitol 100 mg

Indomethacin

Intervention Type: DRUG

Subjects will receive six 25 mg capsules of Indomethacin (immediate release). The subjects will take 3 capsules 8 hours before the timing of visit 5 (before fasting), and 3 additional capsules 30 minutes before visit 5.

13C mannitol

Intervention Type: DIETARY_SUPPLEMENT

13C mannitol 100 mg

Lactulose

Intervention Type: DIETARY_SUPPLEMENT

lactulose 1 g

Interventions

12C mannitol

12C mannitol 100 mg

Intervention Type: DIETARY_SUPPLEMENT

Indomethacin

Subjects will receive six 25 mg capsules of Indomethacin (immediate release). The subjects will take 3 capsules 8 hours before the timing of visit 5 (before fasting), and 3 additional capsules 30 minutes before visit 5.

Intervention Type: DRUG

13C mannitol

13C mannitol 100 mg

Intervention Type: DIETARY_SUPPLEMENT

Lactulose

lactulose 1 g

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

Indocin

Eligibility Criteria

Inclusion Criteria

• Age (yr) 18 to 65
• No abdominal surgery (except appendectomy and cholecystectomy, others may be considered)

Exclusion Criteria

• History of irritable bowel syndrome (IBS), inflammatory bowel disease (IBD) (Crohn's disease or ulcerative colitis), microscopic colitis or celiac disease.
• Use of tobacco products within the past 6 months (since nicotine may affect intestinal permeability)
• Use of nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin within seven days of first permeability test (as NSAIDs affect intestinal permeability) and second permeability test (except those administered for the study)
• Use of oral corticosteroids within the previous 6 weeks
• Ingestion of artificial sweeteners such as Splenda® (sucralose), NutraSweet® (aspartame), lactulose or mannitol within two (2) days of each permeability test and endoscopy procedure date, 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 within 7 days each permeability test and endoscopy procedure date. This includes drugs such as serotonin (5-HT) agents, narcotics, anticholinergics, anti-nausea medications, any medications for diarrhea or constipation.
• Antibiotics within 7 days each permeability test and endoscopy procedure date
• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Madhusudan (Madhu) Grover, MBBS

Madhusudan Grover, MBBS

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Madhusudan Grover, MBBS

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Countries

United States

Other Identifiers

15-003603

Identifier Type: -

Identifier Source: org_study_id