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

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

Study Overview

• Status: Completed
• Conditions: Impaired Small Intestinal Permeability
• Intervention / Treatment: Dietary supplement: 12C mannitol; Drug: Indomethacin; Dietary supplement: 13C mannitol; Dietary supplement: Lactulose

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 Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Healthy Volunteers

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Dietary supplement: 12C mannitol; 12C mannitol 100 mg; Drug: 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.; Other Names: Indocin; Dietary supplement: 13C mannitol; 13C mannitol 100 mg; Dietary supplement: Lactulose; lactulose 1 g

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Colonic permeability as measured by change in mannitol excretion between 8 and 24 hours		8 hours, approximately 24 hours
Change in mannitol excretion at 24 hours		baseline, approximately 24 hours
Change in lactulose-mannitol excretion assay at 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.	baseline, approximately 2 hours
Change in hour lactulose-mannitol excretion assay between 8 and 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.	8 hours, approximately 24 hours

Collaborators and Investigators

• Sponsor: Mayo Clinic

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Actual): July 17, 2018
• Study Completion (Actual): July 17, 2018

Study Registration Dates

• First Submitted: September 22, 2015
• First Submitted That Met QC Criteria: November 10, 2015
• First Posted (Estimate): November 13, 2015

Study Record Updates

• Last Update Posted (Actual): June 4, 2019
• Last Update Submitted That Met QC Criteria: June 3, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Gastrointestinal Agents; Natriuretic Agents; Diuretics, Osmotic; Diuretics; Reproductive Control Agents; Gout Suppressants; Tocolytic Agents; Lactulose; Mannitol; Indomethacin
• Other Study ID Numbers: 15-003603

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided