FRESCO is a randomized, longitudinal, prospective, three arm, multicentre, double blind study to determine safety and efficacy of repeated faecal microbiota transplantation (FMT) or faecal microbiota filtrate transplantation (FMFT) compared to placebo using oral, frozen capsules in 174 randomized patients with mild to moderate active Ulcerative Colitis.
Ulcerative colitis (UC) is a chronic inflammatory bowel disease with significant morbidity and mortality. Although the precise cause remains unknown, disturbances in the intestinal microbial community and changes in the crosstalk between the microbiota and the mucosal immune system have been linked to its pathogenesis. As current therapies are limited, there is a medical need for new therapies. Faecal microbiota transplantation (FMT) has been proven to be effective in managing relapsing Clostridium difficile infection (CDI) and preliminary results indicated that also the transfer of filtrates of donor stool (FMFT) drives gastrointestinal microbiota changes and eliminate symptoms in CDI patients. FRESCO is a randomized, longitudinal, prospective, three arm, multicentre, double blind study to determine safety and efficacy of repeated FMT or FMFT compared to placebo using oral, frozen capsules in 174 randomized patients with mild to moderate active UC. The primary outcome will be clinical and endoscopic remission at week 12. This proposal aims to examine: (a) the efficacy of FMT / FMFT as a therapy for active UC, (b) the safety of FMT / FMFT in patients with UC and (c) the microbial and inflammable changes that occur after FMT / FMFT, to help understand how and why it works in this group of patients. All analyses will be conducted in both intention-to-treat (primary) and per-protocol (sensitivity analyses) populations, and the differences in remission rates and relapse rates between the groups will be statistically analysed to determine the efficiency of FMT versus FMFT.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
129
Multidonor stool mixed with sterile normal saline, homogenized, filtered, centrifuged, air pressure filtered, encapsulated in hypromellose capsules and frozen.
Multidonor stool mixed with sterile normal saline, homogenized, filtered, encapsulated in hypromellose capsules and frozen.
Sterile saline encapsulated in hypromellose capsules and frozen.
Jena University Hospital
Jena, Thuringia, Germany
RECRUITINGclinical remission
The primary outcome will be clinical remission at week 12 post first transfer of FMFT or FMT, defined by Mayo score ≤ 2, all subscores ≤ 1; additionally patients unavailable at the week 12 follow-up will be included as non-responders (i.e. counted no remission).
Time frame: 12 weeks
steroid-free clinical remission
steroid-free clinical remission at week 12 post first transfer of FMFT or FMT, with a minimum of steroid free time of 4 weeks (week 8 to 12)
Time frame: 12 weeks
clinical response
clinical response is defined by decrease in partial Mayo score by more than 3 points and a minimum decrease of 30% from output value and additional bleeding subscore by more than 1 point or absolute sub-score of 0-1
Time frame: 12 weeks
change in quality of life
quality of life is assessed at week 0,4,8,12 for short-term efficacy and for long-term efficacy at week 24,36 and 52 post first transfer by Inflammatory Bowel Disease Quality of Life Questionnaire (IBDQ). The IBDQ is a 32-item self-rated questionnaire with 4 domains (bowel symptoms, emotional function, social function, systemic symptoms). Each item is rated on a seven-point Likert Scale. The total score ranges from 32 to 224 points with higher scores reflecting better well-being.
Time frame: 52 weeks
endoscopic remission
endoscopic remission at week 12 post first transfer of FMFT or FMT, with a score between 0 and 3, (0 = Normal or inactive disease, 1 = mild inflammatory activity, 2 = moderate disease, 3 = severe disease)
Time frame: 12 weeks
mucosal inflammation - measured through fecal calprotectin
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Sozialstiftung Bamberg
Bamberg, Germany
RECRUITINGCharité Berlin
Berlin, Germany
RECRUITINGDRK Kliniken Berlin Westend
Berlin, Germany
RECRUITINGHavelhöhe
Berlin, Germany
RECRUITINGKrankenhaus Waldfriede
Berlin, Germany
RECRUITINGUniversitätsklinikum Carl Gustav Carus Dresden
Dresden, Germany
RECRUITINGFAU Universität Erlangen-Nürnberg
Erlangen, Germany
RECRUITINGAgaplesion Markus Krankenhaus
Frankfurt, Germany
RECRUITINGUniversitätsklinik Freiburg
Freiburg im Breisgau, Germany
RECRUITING...and 10 more locations
mucosal inflammation in stool samples at week 0, 4, 8, 12, 24, 36, 52 post first transfer of FMFT or FMT
Time frame: 52 weeks
microbiome analysis
analysis of stool samples at week 0, 4, 8, 12, 24, 36, 52 post first transfer of FMFT or FMT regarding microbiome diversity and composition
Time frame: 52 weeks
virome analysis
analysis of stool samples at week 0, 4, 8, 12, 24, 36, 52 post first transfer of FMFT or FMT regarding virome composition
Time frame: 52 weeks
MAYO Total Score
Comparison of the MAYO total Score between the 3 Arms (FMFT, FMT and Placebo)
Time frame: 52 weeks
Histological mucosal inflammation - Nancy index
Analysis of obtained mucosa biopsies at week 0 and 12, regarding disease activity graded with the Nancy index
Time frame: 12 weeks
Safety - adverse events and severe adverse events
adverse events and severe adverse events in the different treatment arms will be recorded
Time frame: 52 weeks