According to the Centers for Disease Control and Prevention, in 2011 in the United States there were almost half a million Clostridium difficile infections, and 1 in 11 patients 65 or older with a health-care–associated C. diff infection died within 30 days of diagnosis.

This bacterial infection causes inflammation of the colon (colitis) and brings risk of hospitalization and death. Most C. diff infections occur in hospitals and nursing homes, and older patients exhibit markedly greater risk of the infection. Certain antibiotics, by disrupting gut flora, create an opening for the infection.

Antibiotics are the first-line treatment, but approximately 20% of patients relapse within weeks, and those who relapse have a 40% risk of a second relapse.“I take care of a lot of people with C. diff, and recurrence is a terrible problem. We have effective treatments, but we struggle with knowing what to do to prevent recurrence,” said David Aronoff, MD, Addison B. Scoville Jr. Professor of Medicine and director of Infectious Diseases at Vanderbilt.

Aronoff has reason to imagine that an inexpensive generic drug called misoprostol might prevent C. diff recurrence.He’ll now test that prospect with the aid of a $7.7 million grant from the Center for Advancing Translational Sciences at the National Institutes of Health.

The 5-year grant will support a phase 2 randomized, clinical trial at three centers: Vanderbilt University Medical Center, the University of North Carolina-Chapel Hill, and Washington University in St. Louis.Investigators will recruit 440 patients age 50 and over experiencing a first episode of C. diff infection, to receive a 2-week course of misoprostol or placebo.

A synthetic prostaglandin developed in 1973, misoprostol is a relatively safe drug once used to prevent gastrointestinal ulcers in people taking daily NSAIDs (aspirin, ibuprofen, etc), but for that use, it has since been replaced by newer alternatives.Aronoff says a combination of evidence has led him to investigate repurposing the drug.Epidemiological evidence shows that misoprostol protects the lining of the gastrointestinal tract, and Aronoff’s previous work shows that NSAIDs worsen disease severity in a mouse model of antibiotic-associated C. diff infection, while misoprostol reduces severity.

Key evidence came from BioVU, Vanderbilt’s biobank linking human DNA samples and genotype data to de-identified electronic health records.A BioVU scan conducted under auspices of the Vanderbilt Institute for Clinical and Translational Research (VICTR) found strong associations between colitis/gastroenteritis and variants in genes that code for the cell receptors targeted by misoprostol.

“I would not have applied for the trial without having a bioinformatics source that suggested this might be a good idea.“When you’re talking about repurposing a drug in older people, one wants to be careful about choosing drugs for that population. Having a bioinformatics-based rationale from BioVU really buttressed our model,” Aronoff said.A successful repurposing trial would open possibilities for improving the formulation of misoprostol to limit side effects and maximize efficacy for preventing infection recurrence, Aronoff said.