Gastroenterology

Gastroenterology

Volume 149, Issue 1, July 2015, Pages 110-118.e4
Gastroenterology

Original Research
Full Report: Clinical—Alimentary Tract
Findings From a Randomized Controlled Trial of Fecal Transplantation for Patients With Ulcerative Colitis

https://doi.org/10.1053/j.gastro.2015.03.045Get rights and content

Background & Aims

Several case series have reported the effects of fecal microbiota transplantation (FMT) for ulcerative colitis (UC). We assessed the efficacy and safety of FMT for patients with UC in a double-blind randomized trial.

Methods

Patients with mild to moderately active UC (n = 50) were assigned to groups that underwent FMT with feces from healthy donors or were given autologous fecal microbiota (control); each transplant was administered via nasoduodenal tube at the start of the study and 3 weeks later. The study was performed at the Academic Medical Center in Amsterdam from June 2011 through May 2014. The composite primary end point was clinical remission (simple clinical colitis activity index scores ≤2) combined with ≥1-point decrease in the Mayo endoscopic score at week 12. Secondary end points were safety and microbiota composition by phylogenetic microarray in fecal samples.

Results

Thirty-seven patients completed the primary end point assessment. In the intention-to-treat analysis, 7 of 23 patients who received fecal transplants from healthy donors (30.4%) and 5 of 25 controls (20.0%) achieved the primary end point (P = .51). In the per-protocol analysis, 7 of 17 patients who received fecal transplants from healthy donors (41.2%) and 5 of 20 controls (25.0%) achieved the primary end point (P = .29). Serious adverse events occurred in 4 patients (2 in the FMT group), but these were not considered to be related to the FMT. At 12 weeks, the microbiota of responders in the FMT group was similar to that of their healthy donors; remission was associated with proportions of Clostridium clusters IV and XIVa.

Conclusions

In this phase 2 trial, there was no statistically significant difference in clinical and endoscopic remission between patients with UC who received fecal transplants from healthy donors and those who received their own fecal microbiota, which may be due to limited numbers. However, the microbiota of responders had distinct features from that of nonresponders, warranting further study. ClinicalTrials.gov Number: NCT01650038.

Section snippets

Ethical Issues

The ethics committee at the study center approved the protocol (Supplementary Appendix 1). All participants provided written informed consent. Monitor visits were performed to ensure that the trial was conducted and documented properly. A Data Safety Monitoring Board (DSMB) unblinded for treatment allocation monitored safety and efficacy of the trial. The study was registered on ClinicalTrials.gov (NCT01650038) and the Dutch trial registry from start of the study (NTR2862). All authors had

Recruitment

From June 24, 2011 through May 28, 2014, fifty patients were recruited. An interim analysis was performed by the DSMB when 20 patients had passed their primary end point visit. Based on an observed treatment effect of less than expected, the DSMB advised a recalculation of sample size when 36 patients had passed their primary end point visit. At the second interim analyses, the DSMB advised to stop the trial due to futility. Three months results of all included patients are presented here.

Discussion

This is the first full report on the results of a proof of concept double-blind placebo-controlled trial of the efficacy of FMT in UC. In our cohort of 48 UC patients with mild to moderately active disease, 2 duodenal infusions of feces from a healthy donor did not result in a statistically significant difference in clinical remission and endoscopic improvement. Our results show that for FMT in UC, it is clearly not “one size fits all.” However, some patients do respond well to FMT, which

Acknowledgments

ClinicalTrials.gov Number: NCT01650038.

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    Conflicts of interest The authors disclose no conflicts.

    Funding This work was supported by MLDS grant 2011 (WO 11-17) to Noortje G. Rossen and NWO-Spinoza grant 2008 to Willem M. de Vos.

    Author names in bold designate shared co-first authorship.

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