12December2017

Fecal Transplantation Using a Novel Conditioning Method for Donor and Recipient in Mild to Moderate Treatment Refractory Colitis in IBD

Arie Levine, ECCO Grant Winner

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Arie LevineArie Levine © ECCO

Fecal microbial transplantation (FMT) is an exciting and evolving methodology to transform the microbiota in microbiota-related diseases. The rationale behind FMT is "transfer of a healthy microbiota" from a donor to a patient with IBD, leading to a change in recipient microbiota towards that of a healthy donor. However, current methods are simplistic. Random healthy donors do not necessarily have an appropriate microbiota, and transferred microbiota may not colonise the recipient’s gut. Diet can rapidly degrade certain taxa or increase others, such that if the recipient diet is not appropriate, donor microbiota expansion may not occur or functionality may be impaired.

The CRAFT UC study utilises a novel second-generation approach to FMT involving a predetermined diet to condition the donor towards specific targeted families and genera and to facilitate microbiota colonisation and expansion in the recipient by using the same diet in the recipient. The diet limits specific  food additives, sources of proteins and fats while including substrates for short chain fatty acid (SCFA) production. Harmonisation of diet between donor and recipient should theoretically allow for better colonisation. In this first RCT we plan to evaluate this method in patients with mild to moderate treatment-refractory Ulcerative Colitis (UC).

Study Objectives

  1. Overall aim of the research project
    We propose to modify FMT in order to achieve better sustained remission rates in treatment-refractory UC. We hypothesise that sustained remission will be improved in conditioned donors and recipients because of better colonisation and functionality of donor microbiota in the recipient. 
  2. We will perform a blinded multicentre multinational randomised controlled trial over 24 months to compare standard FMT via colonoscopy to FMT with conditioned donor and recipient, with translational arms evaluating changes in the microbiome.

Methodology

This is a three-arm single-blinded prospective randomised controlled study in 86 adults with mild to moderate drug-refractory UC. The study will be performed at four hospitals in Tel Aviv, Rome and Milan. Healthy screened donors will donate stool, then undergo a 10- to 14-day diet and then donate additional "conditioned" samples. Group 1 will receive standard FMT with non-conditioned stool via colonoscopy at day 0 and FMT enemas on days 2 and 14. Group 2 will receive stools from the same donors but after conditioning  with dietary conditioning of the recipient, and group 3 (10 pts) will receive the recipient diet alone. Patients will be seen at weeks 0, 2, 8, 12 and 20. Microbiome analysis (16S) will be performed in Paris by Professor Harry Sokol.

The primary endpoint is remission by SCCAI score <5 at week 8. We will evaluate  Mayo endoscopic scores (week 8) and changes in the microbiome and SCFA for both donor and recipient.

CoPIs: Nitsan Maharshak, Iris Dotan, Israel; Franco Scaldaferri, Silvio Danese, Italy;  Harry Sokol, France

Posted in ECCO News, Committee News, SciCom, Volume 12, Issue 4

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