To explore the long-term outcomes of treatment for recurrent C diff, NIAID has launched a new trial that will follow patients for 4 years to assess the safety of fecal microbiota transplants.
Multiple research studies have indicated that fecal microbiota transplantation (FMT) is an effective method for curing recurrent Clostridium difficile (C diff) infections, yet long-term safety has not been verified.
Now, the National Institutes of Allergy and Infectious Disease (NIAID) has obtained an investigational new drug application from the US Food and Drug Administration to evaluate FMT in a clinical setting.
At the 6th International C diff Awareness Conference and Health EXPO, November 8, 2018, in Philadelphia, Pennsylvania, Sahil Khanna, MBBS, MS, an associate professor of medicine in the department of gastroenterology at the Mayo Clinic, highlighted the available information about the efficacy of fecal transplants for C diff in an interview with Contagion®.
“What we've learned over the years is that FMT, or fecal transplantation, is efficacious more than 85% to 90% of times in patients who have this deadly recurrent infection,” Dr. Khanna said. “We've also learned that it does not matter what donor it comes from as long donors are screened rigorously. [Furthermore,] fresh stool or frozen stool are similarly efficacious to prevent future recurrent C diff infection.”
Investigators with NIAID, which is part of the National Institutes of Health, are now enrolling volunteer participants into a multi-center trial at Emory University in Atlanta; Duke University Medical Center in Durham, North Carolina; and Vanderbilt University Medical Center in Nashville, Tennessee. All of these institutions are Vaccine and Treatment Evaluation Unit facilities, part of a network funded by NIAID.
Physicians use various routes to administer FMTs, which can include oral pills, upper gastrointestinal endoscopy, colonoscopy, and enema. In order to gather data on standardizing the FMT process, the new trial will focus solely on the safety and efficacy of FMT delivered via enema to patients with recurrent C diff associated diseases.
The trial, led by Nadine Rouphael, MD, associate professor in the Division of Infectious Diseases at Emory University, is designed to enroll 162 volunteer participants aged 18 years or older who have had 2 or more C diff-associated disease episodes within the past 6 months. Volunteers will be enrolled in the trial once recurrent C diff diarrhea symptoms have subsided after completing a standard course of antibiotics such as metronidazole, oral vancomycin, or oral fidaxomicin.
Participants will be randomized at enrollment to 1 of 2 study groups. The trial is partially blinded so that the participants and the investigators involved in the study will not know who is assigned to which group.
The first group of 108 participants will receive an anti-diarrheal medication and a stool transplant delivered by retention enema. The second group, made up of 54 participants, will take an anti-diarrheal medication and receive a placebo solution, which has been colored to resemble a stool transplant, delivered by retention enema.
Participants in either of the study groups whose stool samples test positive for C diff following the enema will receive an active stool transplant for a maximum of 2 FMTs. If a C diff infection follows the receipt of 2 FMTs, the participant will be referred to another available treatment option at the institution.
Each participant will be required to provide a stool and blood samples either 1 year from the date of their effective treatment or from the date of their last treatment if the treatment was unsuccessful. Investigators will monitor the stool sample for changes in microbiome diversity and the presence of infectious pathogens and will examine the blood sample for metabolic syndrome markers.
The participants will be monitored for adverse side effects for 3 years after completing treatment for recurrent C diff. Additionally, investigators will continue to collect information on any new onset of C diff-related medical conditions, or other serious health issues.