As the practice of fecal microbiota transplantation to treat recurrent Clostridium difficile infection continues to evolve, a growing number of researchers have expressed interest in studying the procedure for other conditions, according to an article published in the February issue of Clinical Gastroenterology and Hepatology.
Even though the mechanism of action behind fecal microbiota transplantation (FMT) remains unclear, "the procedure results in restoration of normal microbial gut ecology," wrote Dr. Colleen Kelly, a gastroenterologist at the Women’s Medicine Collaborative, Providence, R.I., and her coinvestigators. "Therefore, it is possible that FMT may become applicable to other conditions associated with intestinal dysbiosis, including inflammatory bowel disease, irritable bowel syndrome, antibiotic-associated diarrhea, and components of metabolic syndrome such as obesity and diabetes."
Source: American Gastroenterological Association
With this in mind and noting that FMT is considered an investigational agent by the Food and Drug Administration, Dr. Kelly and her associates set out to provide guidance to other investigators and clinicians on how to prepare an investigational new drug application (IND) for the Center for Biologics Evaluation and Research to study FMT for recurrent C. difficile infection (R-CDI). "Because of the complexity of IND applications and their burden on a physician, the FDA announced its intention to exercise enforcement discretion regarding IND applications for use of FMT to treat R-CDI," the authors explained (doi:10.1016/j.cgh.2013.09.060). "In these cases, an IND is encouraged but not required. At this time, this decision decreases the need for INDs to treat individual patients with R-CDI. However, an IND for the use of FMT is still required for indications other than CDI for research purposes."
The IND application can have only one sponsor: the investigator or clinician who applies for it. After that is secured, 10 basic elements are required to complete the IND application, according to the authors. These include product name/chemical structure, proposed indications, dosage and route of administration, background about the therapy, and information regarding chemistry, manufacturing, and controls. "The contents of this section vary depending on the source/form of donor material," wrote the authors, who indicated that they hold approved INDs to use FMT in patients with CDI and inflammatory bowel disease. For example, "if the sponsor decides to seek an IND for frozen material, they will need to provide detail about how donor stool will be processed and stored."
Other basic elements of an IND application, according to the article, include a clinical data summary, an FMT treatment protocol that includes plans for clinical follow-up of treated patients and adverse event reporting, an explanation of the risks associated with FMT, and a safety-monitoring protocol that "may consist of symptom diaries maintained by patients/subjects and follow-up telephone contacts and clinic visits."
Dr. Kelly and her associates emphasized that their recommendations are "only a guide to all the elements necessary to put together a protocol and an FDA application and a starting point for the new IND sponsor." They added that minimal requirements for donor testing "are likely to change over time. Some testing that is currently merely recommended may become absolute requirements or may be found unnecessary."
The National Institutes of Health provided funding support for the article. One of the authors, Dr. Alexander Khoruts, has received research funding from CIPAC LLC. The other authors said they had no relevant financial conflicts to disclose.
