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Transfer of FRozen Encapsulated Multidonor Stool Filtrate for Active Ulcerative COlitis (FRESCO)

Primary Purpose

Ulcerative Colitis, Inflammatory Bowel Diseases

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
encapsulated faecal microbiota filtrate
encapsulated faecal microbiota
Placebo
Sponsored by
Jena University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ulcerative Colitis focused on measuring fecal transplantation, multidonor fecal transplantation

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Prior endoscopic confirmation of UC of at least 6 months AND with a minimum disease extent of 15 cm from the anal verge.
  • Having active disease, defined with a Mayo Score between 4-9 and Mayo endoscopic subscore >1

  • May be receiving the following drugs (subjects on these therapies must be willing to remain on stable doses for the noted times

    • 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)
    • 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.
  • 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:

  • Crohn's disease or indeterminate colitis or proctitis alone
  • Acute abdomen or other clinical emergencies requiring emergent management (e.g. bowel obstruction, perforation and/or abscess, previous bowel surgery)
  • Concurrent gastrointestinal infections
  • Other causes of diarrhoea
  • Congenital or acquired immunodeficiency, severe comorbidities (e.g. diabetes mellitus, cancer, systemic lupus, decompensated cirrhosis, recent malignancy in the last 5 years)
  • Pregnancy
  • Patients who are unable or unwilling to undergo colonoscopy, conscious sedation with colonoscopy
  • Previous treatment with TNF- or integrin-antibodies
  • Any antibiotic use within the last 3 months
  • Participation in a clinical trial within the last 3 months
  • Prior history of FMT
  • Probiotic use within 30 days of start date

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Active Comparator

    Sham Comparator

    Arm Label

    faecal microbiota filtrate

    faecal microbiota

    Placebo

    Arm Description

    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.

    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.

    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.

    Outcomes

    Primary Outcome Measures

    clinical remission
    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
    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
    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
    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.

    Full Information

    First Posted
    February 14, 2019
    Last Updated
    September 8, 2021
    Sponsor
    Jena University Hospital
    Collaborators
    German Federal Ministry of Education and Research
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03843385
    Brief Title
    Transfer of FRozen Encapsulated Multidonor Stool Filtrate for Active Ulcerative COlitis
    Acronym
    FRESCO
    Official Title
    Longterm Transfer of FRozen Encapsulated Multidonor Stool Filtrate or Encapsulated Multidonor Microbiome for Chronic Active Ulcerative COlitis
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2021
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    October 2021 (Anticipated)
    Primary Completion Date
    October 2023 (Anticipated)
    Study Completion Date
    November 2023 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Jena University Hospital
    Collaborators
    German Federal Ministry of Education and Research

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. 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.
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Ulcerative Colitis, Inflammatory Bowel Diseases
    Keywords
    fecal transplantation, multidonor fecal transplantation

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2, Phase 3
    Interventional Study Model
    Parallel Assignment
    Model Description
    Patients will be randomized 1:1:1 to receive intensive dosing multi-donor FMFT or FMT as therapeutic strategies or saline as a placebo comparator. To achieve balanced distributions for pretreatment factors, we propose to apply stratified (stratum 1: no steroids / steroids / thiopurines / steroids and thiopurines; stratum 2: "participating centre") block randomization of variable block sizes.
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Masking Description
    To address "concealment of allocation", the 1:1:1 randomization will be done centrally and each patient who is randomized and who received one of the compared treatments is part of the full analysis set (ITT analysis set).
    Allocation
    Randomized
    Enrollment
    174 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    faecal microbiota filtrate
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    faecal microbiota
    Arm Type
    Active Comparator
    Arm Description
    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.
    Arm Title
    Placebo
    Arm Type
    Sham Comparator
    Arm Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    encapsulated faecal microbiota filtrate
    Other Intervention Name(s)
    FMFT
    Intervention Description
    Multidonor stool mixed with sterile normal saline, homogenized, filtered, centrifuged, air pressure filtered, encapsulated in hypromellose capsules and frozen.
    Intervention Type
    Drug
    Intervention Name(s)
    encapsulated faecal microbiota
    Other Intervention Name(s)
    FMT
    Intervention Description
    Multidonor stool mixed with sterile normal saline, homogenized, filtered, encapsulated in hypromellose capsules and frozen.
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Other Intervention Name(s)
    Encapsulated sterile saline
    Intervention Description
    Sterile saline encapsulated in hypromellose capsules and frozen.
    Primary Outcome Measure Information:
    Title
    clinical remission
    Description
    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).
    Time Frame
    12 weeks
    Secondary Outcome Measure Information:
    Title
    steroid-free clinical remission
    Description
    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).
    Time Frame
    12 weeks
    Title
    clinical response
    Description
    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
    Time Frame
    12 weeks
    Title
    change in quality of life
    Description
    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

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Prior endoscopic confirmation of UC of at least 6 months AND with a minimum disease extent of 15 cm from the anal verge. Having active disease, defined with a Mayo Score between 4-9 and Mayo endoscopic subscore >1 May be receiving the following drugs (subjects on these therapies must be willing to remain on stable doses for the noted times 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) 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. 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: Crohn's disease or indeterminate colitis or proctitis alone Acute abdomen or other clinical emergencies requiring emergent management (e.g. bowel obstruction, perforation and/or abscess, previous bowel surgery) Concurrent gastrointestinal infections Other causes of diarrhoea Congenital or acquired immunodeficiency, severe comorbidities (e.g. diabetes mellitus, cancer, systemic lupus, decompensated cirrhosis, recent malignancy in the last 5 years) Pregnancy Patients who are unable or unwilling to undergo colonoscopy, conscious sedation with colonoscopy Previous treatment with TNF- or integrin-antibodies Any antibiotic use within the last 3 months Participation in a clinical trial within the last 3 months Prior history of FMT Probiotic use within 30 days of start date
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Andreas Stallmach, Prof.
    Phone
    +49-3641-9
    Ext
    324401
    Email
    andreas.stallmach@med.uni-jena.de
    First Name & Middle Initial & Last Name or Official Title & Degree
    Philip C Grunert, MD
    Phone
    +49-3641-9
    Ext
    324465
    Email
    philip.grunert@med.uni-jena.de
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Andreas Stallmach, Prof.
    Organizational Affiliation
    Jena University Hospital
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided
    Citations:
    PubMed Identifier
    35193638
    Citation
    Stallmach A, Grunert P, Stallhofer J, Loffler B, Baier M, Rodel J, Kiehntopf M, Neugebauer S, Pieper DH, Junca H, Tannapfel A, Merkel U, Schumacher U, Breternitz-Gruhne M, Heller T, Schauer A, Hartmann M, Steube A. Transfer of FRozen Encapsulated multi-donor Stool filtrate for active ulcerative Colitis (FRESCO): study protocol for a prospective, multicenter, double-blind, randomized, controlled trial. Trials. 2022 Feb 22;23(1):173. doi: 10.1186/s13063-022-06095-1.
    Results Reference
    derived

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