A national research consortium sponsored by the National Institutes of Health (NIH) and led by Emory University School of Medicine recently began enrolling patients in a clinical trial examining whether fecal microbiota transplantation (FMT) -- putting stool from a healthy donor in the colon of a recipient – delivered by enema is safe and able to prevent recurrent Clostridium difficile (C.diff) associated disease (CDAD), a potentially life-threatening diarrheal illness.

C.diff is a significant problem in health care facilities and causes an estimated 15,000 deaths in the United States each year. The randomized, controlled trial aims to provide much-needed data on the efficacy and long-term safety of FMT delivered by enema to cure recurrent C. diff infections.

Nadine Rouphael, MD, associate professor, Division of Infectious Diseases at Emory University School of Medicine, is principal investigator for the multi-site study, which aims to evaluate the safety and efficacy of FMT for patients with recurrent CDAD. Tanvi Dhere, MD, and Colleen Kraft, MD, directors of the FMT program at Emory, are co –investigators for the study.

The trial will take place at Emory University, Duke University Medical Center and Vanderbilt University Medical Center. Each location is a Vaccine and Treatment Evaluation Unit (VTEU), a network of clinical research sites funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH.

Investigators aim to enroll 162 volunteer participants 18 years or older who have had two or more episodes of C.diff within the previous six months.

C. diff, is a bacterium that infects the colon and can cause diarrhea, fever and abdominal pain. CDAD most commonly occurs in hospitalized older adults who have recently taken antibiotics. Although antibiotics can cure infections, they can also alter the gut microbiome and allow C. diff to grow and cause severe inflammation of the colon.

People with CDAD are usually treated with a course of antibiotics; however, CDAD returns in approximately 20 percent of people, according to the Centers for Disease Control and Prevention (CDC).

Physicians perform FMT using various routes of administration, including oral pills, upper gastrointestinal endoscopy, colonoscopy, and enema. Multiple research studies have indicated that FMT is an effective method for curing patients with repeat C. diff infections and restoring a healthy and diverse gut microbiome. The trial is part of an effort to gather data on how best to standardize the FMT process. The long-term outcomes of FMT delivered by enema, for example, have not been established, and more research is needed to determine the precise mechanisms that make FMT effective in curing recurrent CDAD.

Volunteers will be randomly assigned to one of two groups. One group will take an anti-diarrheal medication and receive an FMT by enema. The second group will take an anti-diarrheal medication and receive a placebo enema. Participants from both groups who have recurrent CDAD in the first week after the first enema will receive an additional FMT. If participants in either group remain symptomatic after receiving two FMTs, they will be referred to other locally available treatment options.

All participants will be evaluated for one year, with researchers studying changes in gut microbial diversity, and markers of metabolic syndrome. To learn more about the long-term outcomes of FMT, the researchers will monitor participants for safety outcomes for three years after completing treatment for recurrent CDAD. They will collect information on any new onset of CDAD, related chronic medical conditions, or any other serious health issues. A Data and Safety Monitoring Board comprising an independent group of non-NIAID experts will periodically review the study data for safety and make recommendations regarding trial modifications or termination.

NIAID submitted an Investigational New Drug (IND) Application to the Food and Drug Administration (FDA) to evaluate FMTs as part of a clinical research study. FDA approved the IND, which allows the trial investigators to obtain stool for FMTs from OpenBiome, a nonprofit stool bank based in Cambridge, Mass. 

For more information, visit ClinicalTrials.gov and search identifier NCT03548051 or call the Hope Clinic at 404 -712-1371