Seven out of nine children with active ulcerative colitis experienced at least a temporary clinical response within 1 week of a series of fecal transplants – with four of the patients staying in complete remission 1 month later.
The procedures represent the first time fecal transplantation has been used to treat ulcerative colitis, Dr. Sachin Kunde and his colleagues reported online in the Journal of Pediatric Gastroenterology and Nutrition (2013 March 29 [doi: 10.1097/MPG.0b013e318292fa0d]).
"Utilization of fecal material transplantation in ulcerative colitis may not be as simple as its use in recurrent C. difficile infection," wrote Dr. Kunde of the Helen DeVos Children’s Hospital, Grand Rapids, Mich., and his coauthors. Still, they said, this early success in a devastating, hard-to-manage disease should be the launching point for larger trials.
Dr. Sachin Kunde
The study group comprised 10 patients who ranged in age from 7 to 20 years. All had mild to moderate, active ulcerative colitis. Disease duration ranged from 1 to 8 years. Participants had stable disease and received medical treatment for at least 2 months before the procedure. Only one patient had used anti–tumor necrosis factor (anti-TNF)-alpha medications.
The intervention consisted of a 5-day series of daily enemas containing fresh stool from a donor. Each of the patients chose an adult donor; most were first-degree relatives. One patient chose a close family friend. The donors took daily over-the-counter stool softeners to produce the required amount – a mean of 90 g/day. This was blended with 250 mL of sterile normal saline, strained, and divided into four 60-mL portions. In each treatment, all four of the portions were infused, each over a 15-minute period.
The patients did not receive any bowel preparation before the procedures. They received the enemas while lying on the left side, and then rotating to the right side and back again to allow the solution to travel into the colon.
Ten patients entered treatment. However, one could not retain the enemas and so was not included in the final analysis. The remaining patients were able to tolerate an enema volume of 75-240 mL (average retention, 165 mL). Retention was not directly related to age, the investigators noted, since the subject who could not retain it was the oldest. Retention times ranged from 3 to 24 hours.
There were no serious adverse events during the study. Patients did report the expected discomfort of left-sided abdominal fullness. One experienced a moderate fever and chills 3 hours after the first two transplants, which spontaneously resolved over 6 hours. For the final three procedures, that patient took prophylactic acetaminophen and diphenhydramine.
Another patient had a low-grade fever after one transplant, which resolved without intervention. There were no cases of sepsis.
One patient experienced a disabling hematochezia 3 weeks after the transplant series. This was judged to be a flare unrelated to the transplant.
In the first week after the transplant series, seven of the nine patients in the analysis (78%) had a clinical response, defined as a decrease of more than 15 points in the Pediatric Ulcerative Colitis Activity Index. Six of the nine (67%) maintained that improvement at 1 month.
Three experienced clinical remission at 1 week, which lasted for 1 month. Two patients had a PUCAI score of 0 from week 3 until the end of the 7-week follow-up period.
The pilot study shows the feasibility of fecal transplants for ulcerative colitis, Dr. Kunde said. But while the technique is similar to that employed in C. difficile treatment, a more prolonged treatment seems necessary to elicit a response in ulcerative colitis.
"In order to better understand how fecal transplants can be used to treat ulcerative colitis, many unanswered questions need to be addressed. We must further investigate standardization of ... preparation, ideal donor selection, ideal route of administration, and optimal duration of scheduling [the transplants] to induce and maintain a clinical response. Most importantly, the effects of fecal material transplant on the colonic microbiome and mucosal inflammation in ulcerative colitis need to be explored."
The Helen Devos Children’s Hospital supported the research. The authors did not disclose any financial relationships.