Kunde S, Pham A, Bonczyk S, et al. Safety, tolerability, and clinical response after fecal transplantation in children and young adults with ulcerative colitis. J Pediat Gastroenterol Nutr. 2013;56(6):597-601.
Prospective, open-label, uncontrolled pilot study
Ten children and young adults (ages 7–21) with mild to moderate ulcerative colitis [pediatric ulcerative colitis activity index (PUCAI) between 15 and 65].
Study Parameters Assessed & Primary Outcome Measures
- Tolerability (ability for subjects to retain 60 mL fecal slurry enema for at least an hour)
- Safety (monitoring and recording any untoward medical event associated with the fecal transplant intervention, whether or not it was definitely caused by the intervention)
- Clinical response (decrease of >15 points in PUCAI, clinical remission defined as decrease in PUCAI to <10)
Study Medication and Dosage
A stool donor was screened to rule out potentially communicable disease. An entire donor bowel movement (average 90 g) was collected a maximum of 6 hours prior to the procedure. The stool was mixed with 250 mL of normal saline in a blender for 1 minute, filtered through 2 layers of gauze, and divided into four 60 mL aliquots. One 60 mL aliquot was administered to the subject in the left decubitus position per rectum over the course of 5 minutes. If the subject was willing and comfortable, one 60mL aliquot was administered every 15 minutes until the entire 240 mL dose was retained. If tolerated, subjects received the intervention daily for 5 days.
The administration of fecal slurry as a medical intervention, also known as fecal microbiota transplantation (FMT) was recently classified by the FDA as a drug and a biological agent.
One subject showed intolerance with immediate leaking of enemas for 3 consecutive days. Otherwise, the intervention was well tolerated (an average of 165 mL retained without leakage for an average of 10 hours).
Fecal retention enemas were associated with a mild feeling of abdominal fullness. Two subjects reported a transient fever (1 received antipyretics) that the authors described as probably related to the fecal transplant. There were no signs of sepsis, and no serious adverse events related to the intervention. Some subjects experienced symptoms (for example, disabling hematochezia 3 weeks after the intervention) that appeared to be related to their baseline UC symptoms and not to the intervention.
Seven subjects showed a clinical response at 1 week, of whom 6 maintained a clinical response at 1 month. Three of the responders achieved clinical remission at 1 week and also maintained remission at 1 month. Median PUCAI score significantly decreased after fecal transplant (P=0.03) compared to baseline.
The administration of fecal slurry as a medical intervention, also known as fecal microbiota transplantation (FMT) was recently classified by the FDA as a drug and a biological agent.1 As such, the FDA has restricted clinicians’ use of FMT to clinical trials, except when used for antibiotic-resistant Clostridium difficile colitis.2 This has led to more widespread use of FMT prepared and administered at home by UC patients and the parents of pediatric UC patients. Can it be done safely and effectively at home? Silverman et al reported a 7-person case series in which they instructed patients with refractory C. difficile colitis to perform home FMT.3 They observed home FMT to be an effective and safe option for patients with chronic relapsing C. difficile infection.
Patients who have UC or other inflammatory bowel disease may request clinicians’ professional opinions, guidance, and assistance around the use of FMT at home. The equipment described by Kunde et al above (home blender, gauze, enema bags, or bottles) are all easily obtained, and the process of blending and administering fecal slurries can be done at home by most people without too much difficulty. Patients may request assistance from a clinician in selecting and obtaining a diluent, ensuring that their donor is free of transmissible disease, and monitoring their health status during and after FMT.
Both Kunde and Silverman used normal saline, which can be difficult to obtain without a prescription, as their diluent. A 2011 systematic review of FMT for recurrent C. difficile infection reported that 20 authors used a normal saline diluent in a total of 196 patients, with an 86% resolution rate, and 1 author used a water diluent in 65 cases, with a 98.5% resolution rate.4 Other clinicians have described using filtered water as their FMT stool diluent with apparent benefit for patients with refractory C. difficile colitis (C. Lee, personal communication, 2012) and inflammatory bowel disease. This gives clinicians the option of providing affordable normal saline for their patients, or taking a more hands-off method that steers clear of FDA grey-zones and letting patients know that easily obtainable filtered water can probably be used to provide the same degree of safety and benefit.
The Fecal Microbiota Transplantation Workgroup (an international group of clinicians with significant experience in FMT) published guidelines for testing donors in 2011.5 They recommended serum testing for HIV, syphilis, and viral hepatitis, and stool testing for ova and parasites, common enteric pathogens, C. difficile, Giardia, Cryptosporidium, Cyclospora, and Isospora. Other authors have suggested testing donor stool more specifically for Blastocystis hominis and Dientamoeba fragilis, and testing donor serum for antibodies to human T-cell lymphotropic virus, cytomegalovirus, Epstein–Barr virus, Strongyloides stercoralis, and Entamoeba histolytica.6
Monitoring Health Status
Kunde et al reported that they did not observe any serious adverse effects that they believed were caused by the intervention. They did observe a febrile response in 2/10 patients who received the intervention, 1 of whom was administered antipyretics. Clinicians should alert patients with inflammatory bowel disease who are self-administering FMT to be aware of a potential febrile response so the clinician can suggest treatment if indicated.
As of this writing, clinicaltrials.gov lists 9 FDA-approved clinical trials studying FMT for C. difficile infection, as well as 7 trials studying FMT for inflammatory bowel disease (not counting Kunde’s completed study), and 1 studying FMT for diabetes.7 As safety and efficacy data becomes available, the FDA may approve FMT for certain indications, and clinicians may have the liberty to use FMT outside of the context of FDA-approved clinical trials. This could include continued support for patients self-administering FMT at home, as well as clinician-supervised donor testing, donor stool collection, fecal slurry preparation, and fecal slurry administration via enema, rectal tube, colonoscope, or nasoduodenal tube.
- Midthun K. Letter to Boland CR, et al. American Gastroenterological Association. http://highroadsolution.com/file_upload_2/files/fda+response+letter+to+fmt+inquiry.pdf. Accessed August 29 2013.
- FDA Center for Biologics Evaluation and Research. Guidance for Industry: Enforcement Policy Regarding Investigational New Drug Requirements for Use of Fecal Microbiota for Transplantation to Treat Clostridium difficile Infection Not Responsive to Standard Therapies. U.S. Food and Drug Administration. http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Vaccines/ucm361379.htm. Accessed August 29, 2013.
- Silverman MS, Davis I, Pillai DR. Success of self-administered home fecal transplantation for chronic Clostridium difficile infection. Clin Gastroenterol Hepatol. 2010;8(5):471-473.
- Gough E, Shaikh H, Manges AR. Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. Clin Infect Dis. 2011;53(10):994-1002.
- Bakken JS, Borody T, Brandt LJ, et al. Treating Clostridium difficile infection with fecal microbiota transplantation. Clin Gastroenterol Hepatol. 2011;9(12):1044-1049.
- van Nood E, Vrieze A, Nieuwdorp M et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013; 31;368(5):407-415.
- Clinical Trials.gov. Gut Microbial Transplantation in Pediatric Inflammatory Bowel Diseases. U.S. National Institutes of Health. http://clinicaltrials.gov/ct2/show/NCT01560819?term=%22fecal+transplant%22+OR+%22Fecal+Transplantation%22+OR+%22fecal+microbiota+transplantation%22&rank=14. Accessed August 29, 2013.