First-in-Human Assessment of Gut Permeability in Crohn’s Disease Patients Using Fluorophore Technology

Background and Aims The dual sugar absorption test (DSAT) as a classic measure of human intestinal permeability has limited clinical utility due to lengthy and cumbersome urine collection, assay variability, and long turnaround. We aimed to determine if the orally administered fluorophore MB-102 (relmapirazin) (MW=372) compares to lactulose (L) (MW=342) and rhamnose (R) (MW=164)-based DSAT as a measure of gut permeability in people with a spectrum of permeability including those with Crohn’s disease (CD). Methods We performed a single center, randomized, open label, crossover study comparing orally administered MB-102 (1.5 or 3.0 mg/kg) to L (1000 mg) and R (200 mg). Adults with active small bowel CD on magnetic resonance enterography (cases) and healthy adults (controls) were randomized to receive either MB-102 or L and R on study day 1, and the other tracer 3-7 days later. Urine was collected at baseline and 1, 2, 4, 6, 8, 10, and 12 hours after tracer ingestion to calculate the cumulative urinary percent excretion of MB-102 and L and R. Results Nine cases and 10 controls completed the study without serious adverse events. Urinary recovery of administered MB-102 correlated with recovery of lactulose (r-squared = 0.83) for all participants. MB-102 urine recovery also tracked with the L:R ratio urine recovery (r-squared=0.57). In controls, the percentages of L and MB-102 recovered were similar within a narrow range unlike in CD patients. Conclusions This first-in-human study of an orally administered fluorophore to quantify gastrointestinal permeability in adults with CD demonstrates that MB-102 is well tolerated, and its recovery in urine mirrors that of percent L and the L:R ratio.