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.