FRESCO: Transfer of FRozen Encapsulated Multidonor Stool Filtrate for Active Ulcerative COlitis
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2/Phase 3 |
Detailed Description
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 mild-moderate UC, (b) the short- and long-term safety of FMT / FMFT in patients with UC and (c) the microbial and immunologic 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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: faecal microbiota filtrate Encapsulated faecal microbiota filtrate . 2×5 frozen capsules by mouth on 5 consecutive days per week (5 days on and 2 days off; week 1 - week 12) with water or apple juice. |
Drug: encapsulated faecal microbiota filtrate
Multidonor stool mixed with sterile normal saline, homogenized, filtered, centrifuged, air pressure filtered, encapsulated in hypromellose capsules and frozen.
Other Names:
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| Active Comparator: faecal microbiota Encapsulated faecal microbiota. 2×5 frozen capsules by mouth on 5 consecutive days per week (5 days on and 2 days off; week 1 - week 12) with water or apple juice. |
Drug: encapsulated faecal microbiota
Multidonor stool mixed with sterile normal saline, homogenized, filtered, encapsulated in hypromellose capsules and frozen.
Other Names:
|
| Sham Comparator: Placebo Placebo: Encapsulated sterile saline. 2×5 frozen capsules by mouth on 5 consecutive days per week (5 days on and 2 days off; week 1 - week 12) with water or apple juice. |
Drug: Placebo
Sterile saline encapsulated in hypromellose capsules and frozen.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- clinical remission [12 weeks]
The primary outcome will be clinical remission at week 12 post first transfer of FMFT or FMT, defined by Mayo score ≤ 2 without any subscore >1 and a Mayo endoscopic subscore 0-1; additionally patients unavailable at the week 12 follow-up will be included as non-responders (i.e. counted no remission).
Secondary Outcome Measures
- steroid-free clinical remission [12 weeks]
steroid-free clinical remission at week 12 post first transfer of FMFT or FMT, defined by Mayo score ≤ 2 without any subscore >1 and a Mayo endoscopic subscore 0-1; additionally patients unavailable at the week 12 follow-up will be included as non-responders (i.e. counted no remission).
- clinical response [12 weeks]
clinical response is defined by decrease in Mayo score by 3 points, decrease in bleeding subscore by 1 as an important patient-related outcome parameter, or absolute sub-score of 0-1
- change in quality of life [52 weeks]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Prior endoscopic confirmation of UC of at least 6 months AND with a minimum disease extent of 15 cm from the anal verge.
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Having active disease, defined with a Mayo Score between 4-9 and Mayo endoscopic subscore >1
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May be receiving the following drugs (subjects on these therapies must be willing to remain on stable doses for the noted times
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oral 5-ASA compounds (5-ASA) compounds provided the dose prescribed has been stable for at least 4 weeks prior to randomization; dose must be stable for first 12 weeks after randomization)
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Azathioprine, 6-Mercaptopurine (6-MP) or Methotrexate (MTX) provided the dose prescribed has been stable for 4 weeks prior to randomization; dose must be stable for first 12 weeks after randomization. Oral corticosteroid therapy (prednisone prescribed at a stable dose ≤ 20 mg/day or budesonide prescribed at a stable dose of ≤ 9 mg/day) provided the dose prescribed has been stable for 2 weeks prior to randomization.
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Ability to understand and willingness to sign informed consent document in patients whom the investigator believes can and will comply with the requirements of the protocol.
Exclusion Criteria:
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Crohn's disease or indeterminate colitis or proctitis alone
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Acute abdomen or other clinical emergencies requiring emergent management (e.g. bowel obstruction, perforation and/or abscess, previous bowel surgery)
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Concurrent gastrointestinal infections
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Other causes of diarrhoea
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Congenital or acquired immunodeficiency, severe comorbidities (e.g. diabetes mellitus, cancer, systemic lupus, decompensated cirrhosis, recent malignancy in the last 5 years)
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Pregnancy
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Patients who are unable or unwilling to undergo colonoscopy, conscious sedation with colonoscopy
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Previous treatment with TNF- or integrin-antibodies
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Any antibiotic use within the last 3 months
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Participation in a clinical trial within the last 3 months
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Prior history of FMT
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Probiotic use within 30 days of start date
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Jena University Hospital
- German Federal Ministry of Education and Research
Investigators
- Study Director: Andreas Stallmach, Prof., Jena University Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- KS2017-114