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

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.

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