Clinical trial NCT02603822: Performance of 13C Mannitol for in Vivo Measurement of Small Intestinal Permeability
Official title: Performance of 13C Mannitol for in Vivo Measurement of Small Intestinal Permeability
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Impaired Small Intestinal Permeability
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2015-11-13
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Small intestine permeability as measured by change in cumulative excretion of mannitol 0-2 hours
timeFrame: baseline, approximately 2 hours
Secondary outcomes:
measure: Colonic permeability as measured by change in mannitol excretion between 8 and 24 hours
timeFrame: 8 hours, approximately 24 hours
measure: Change in mannitol excretion at 24 hours
timeFrame: baseline, approximately 24 hours
measure: Change in lactulose-mannitol excretion assay at 2 hours
timeFrame: baseline, approximately 2 hours
measure: Change in hour lactulose-mannitol excretion assay between 8 and 24 hours
timeFrame: 8 hours, approximately 24 hours
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Madhusudan Grover, MBBS
role: PRINCIPAL_INVESTIGATOR
References: