The TURN 2 trial, transplantation of feces in ulcerative colitis; improving efficacy

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) of the colon that affects approximately 40,000 individuals in The Netherlands. Complaints such as abdominal pain, cramps and bloody diarrhoea usually start in early adulthood and lead to life-long substantial morbidity. The cause of UC is unknown, but the prevailing hypothesis is that there is a disproportionate immune response to the host gut microbiota. Many observational studies have shown a dysbiosis of the gut microbiota in UC. An attractive way to modulate this interaction is to radically reset the microbiota by fecal microbiota transplantation (FMT) from a healthy individual to a patient. We recently completed a randomized trial comparing FMT from a healthy donor with infusion of autologous feces in UC patients. In this phase 2a proof-of-concept trial, there was no statistically significant difference in clinical and endoscopic remission between patients with UC who received fecal transplants from healthy donors (30.4%) and those who received their own fecal microbiota (20.0%), which may be due to limited numbers. However, the microbiota of responders had distinct features from that of nonresponders, warranting further study. We next found that patients who received donor feces from a healthy individual rich in certain Clostridium clusters IV and XIVa and with a low abundance of Ruminococcus gnavus, had a high chance of sustained clinical remission. We hypothesize that by preselecting favorable donors, anaerobic fecal collection, augmenting engraftment by rigorous prior bowel cleansing and dual and repetitive administration of >60 gr of feces per donation, we can boost the treatment efficacy of FMT in UC patients. Furthermore, IBD is associated with primary sclerosing cholangitis (PSC) and a a recent pilot study described promising results in liver enzymes levels in PSC/UC patients.Therefore, we hypothesize that FMT can affect disease activity, captured by MRI liver images and post-processing analysis, of PSC in patiënts with PSC/UC.

We hypothesize that the treatment efficacy of FMT in UC can be augmented by anaerobic stool collection, appropriate donor selection based on their microbiota profile and by enhancing the engraftment by dual route administration. Furthermore, we hypothesize that FMT can affect disease activity of PSC, captured by MRI liver images and post-processing analysis, in patiënts with PSC/UC.

Week -4,0,1,2,3,4,8,18,39,52

Arm 1: Patients will be treated with faecal transplantation, processed for duodenal and rectal administration.
Arm 2: Patients will be treated with their own faeces (placebo), processed for duodenal and rectal administration.
PSC/UC subgroup will undergo a MRI liver at baseline and 8 weeks after faecal transplantation.