Ulcerative Colitis (UC) is a chronic debilitating disease with an increased risk of bowel cancer. Management relies on life-long anti-inflammatory/immunosuppressive agents and, in some cases, patients need colectomy. There is a pressing need for better and more effective medical treatments to reduce the need for surgery and reduce the long-term cancer risk.
Recently we have begun to understand the relationship between ourselves and the many bacteria which share our gastrointestinal tract. What is becoming clearer is the vital role these bacteria play in maintaining health and the damage that can result when the delicate partnership between us and our gut bacteria is disrupted. We now know that there is a difference in the proportion of various colonic bacteria between people with and without UC. It is believed that this difference is related to the colonic inflammation seen in people with UC and that changing the balance of bacteria may have a beneficial effect in reducing the inflammation.
There have been numerous small studies concerning the effects of replacing the bacteria in the gut of patients with UC using probiotics which have been disappointing because the products lack bacterial diversity and concentration. In contrast, Faecal Microbial Transplant (FMT), which is a technique of attempting to alter the gut bacteria makeup of a patient with UC, with bacteria derived from a healthy person, involves the transfer of potentially an entire dense colonic microbial community. In this regard, FMT represents a very low-cost, potentially paradigm-changing, treatment for UC. In theory this treatment would, for the first time, address the cause of the disease rather that reactively treating the resulting inflammation.
FMT has been administered by both the colonic route and via a nasogastric tube (NGT). This latter method has been particularly successful in treating colitis caused by clostridium difficile infection (C Diff). In general, the results of FMT in UC have been encouraging and the treatments have been administered without causing harm. However, these studies in most part have been ‘uncontrolled’ with no comparison between the FMT treatment and an alternative therapy to accurately gauge the effect of FMT in UC. In addition the variability in design and processes used makes the results of these studies difficult to compare. To date, there have been few fully published randomised controlled trials in this field.
The STOP-Colitis trial is a planned 2-stage investigation. The first stage is a pilot trial to determine the optimum route of FMT delivery for the treatment of UC, and secondly, the efficacy of such treatment in patients with active UC which is refractory to standard treatment. At the end of the pilot an independent oversight committee will decide (1) which (if any) of the two routes of FMT delivery to take forward to the main trial; and (2) whether a full randomised control trial (RCT) is feasible (based on a review of the pilot data in terms of assessing treatment efficacy, tolerability, patient adherence to allocated treatment and qualitative perspectives on FMT and trial experience). We propose to proceed forward to the main RCT taking the preferred method into a randomised double-blind, placebo-controlled trial with an efficacy outcome measure of clinical remission.
Further details of the RCT will follow when available.