RESTORE-UC trial
“Fecal microbiota transplantation is a new emerging strategy in the treatment of active ulcerative colitis,” Dr. Caenepeel observed during her presentation. At the time the study was started in 2017 there had been four other studies, with “very heterogeneous” designs in terms of the samples used, the placebos given, the delivery of FMT, and the primary endpoints. The idea of superdonor samples also came out of those trials.
So the aim was to try to standardize practice and set up a trial “to examine if we could increase the FMT success rate in our active ulcerative colitis patients by strictly preselecting our donors; by standardized FMT preparation; and a standardized and repeated FMT administration,” Dr. Caenepeel said.
RESTORE-UC was a multicenter, randomized, double-blind, and sham-controlled trial conducted in seven Belgian hospitals. A predefined futility analysis was performed when 66% (n = 72) of the proposed 108 patients had been recruited. Of these, 36 receive autologous FMT and 30 received superdonor FMT.
“We put the emphasis on standardization. This started already with our donor selection,” Dr. Caenepeel said. From a potential 57 healthy donors, 15 were selected and altogether provided more than 500 samples that were then whittled down to the ones that provided the “best” microbial content.
FMT or autologous samples delivered four times – first by sigmoidoscopy and then at weekly intervals by rectal enema. Every patient received the same donor material, Dr. Caenepeel stressed, containing the same enterotype and concentration.
In addition to the primary endpoint of steroid-free endoscopic and clinical remission at Week 8, secondary endpoints included steroid-free clinical remission, steroid-free clinical response, steroid-free endoscopic remission, and steroid-free endoscopic response. Again, however, no significant differences were seen between the two study arms.
Two serious adverse events were seen in the trial, both occurring in the autologous sample group; these were dysuria/constipation and a worsening of colitis that needed surgery.
In discussion, Walter Reinisch, MD, the director of the inflammatory bowel disease study group at the Medical University of Vienna, picked up on why the study may have been negative. He observed that using a steroid-free endoscopic endpoint, where the Mayo score was zero, may have been a factor. A result of 19% at week 8 was not insignificant, he said, observing “if studies from big sponsors would get these results, they would be very happy.”
Perhaps the trials to date have been a little too simplistic by looking at the donor’s microbiota, Dr. Caenepeel. “It goes much further than microbiota,” she said. Thus, future work will perhaps look at the genetics and immunity of those undergoing FMT, she suggested.
Dr. Caenepeel, Dr. Kamm, and Dr. Reinisch had no conflicts of interest to disclose.