Transfer of FRozen Encapsulated Multidonor Stool Filtrate for Active Ulcerative COlitis (FRESCO)
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT03843385 |
Recruitment Status :
Recruiting
First Posted : February 18, 2019
Last Update Posted : November 24, 2023
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Ulcerative Colitis Inflammatory Bowel Diseases | Drug: encapsulated faecal microbiota filtrate Drug: encapsulated faecal microbiota Drug: Placebo | Phase 3 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 174 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Intervention Model Description: | Patients will be randomized 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: "biologicals yes/no"; stratum 2: "participating centre") block randomization. |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Masking Description: | To address "concealment of allocation", the 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). |
Primary Purpose: | Treatment |
Official Title: | Longterm Transfer of FRozen Encapsulated Multidonor Stool Filtrate or Encapsulated Multidonor Microbiome for Chronic Active Ulcerative COlitis |
Actual Study Start Date : | January 31, 2023 |
Estimated Primary Completion Date : | January 2025 |
Estimated Study Completion Date : | July 2026 |
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 cool drink.
|
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 Name: FMFT |
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 cool drink.
|
Drug: encapsulated faecal microbiota
Multidonor stool mixed with sterile normal saline, homogenized, filtered, encapsulated in hypromellose capsules and frozen.
Other Name: FMT |
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 cool drink.
|
Drug: Placebo
Sterile saline encapsulated in hypromellose capsules and frozen.
Other Name: Encapsulated sterile saline |
- clinical remission [ Time Frame: 12 weeks ]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).
- steroid-free clinical remission [ Time Frame: 12 weeks ]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)
- clinical response [ Time Frame: 12 weeks ]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
- change in quality of life [ Time Frame: 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.
- endoscopic remission [ Time Frame: 12 weeks ]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)
- mucosal inflammation - measured through fecal calprotectin [ Time Frame: 52 weeks ]mucosal inflammation in stool samples at week 0, 4, 8, 12, 24, 36, 52 post first transfer of FMFT or FMT
- microbiome analysis [ Time Frame: 52 weeks ]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
- virome analysis [ Time Frame: 52 weeks ]analysis of stool samples at week 0, 4, 8, 12, 24, 36, 52 post first transfer of FMFT or FMT regarding virome composition
- MAYO Total Score [ Time Frame: 52 weeks ]Comparison of the MAYO total Score between the 3 Arms (FMFT, FMT and Placebo)
- Histological mucosal inflammation - Nancy index [ Time Frame: 12 weeks ]Analysis of obtained mucosa biopsies at week 0 and 12, regarding disease activity graded with the Nancy index
- Safety - adverse events and severe adverse events [ Time Frame: 52 weeks ]adverse events and severe adverse events in the different treatment arms will be recorded
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years to 75 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Age between 18 and 75 years
- 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 4-10 and Mayo endoscopic subscore >1
- Failure of conventional therapy or treatment with biologicals and / or small molecules.
-
previous medical therapy:
- oral 5-ASA compounds (5-ASA); stable dosing for 4 weeks before randomization;
- Azathioprine, 6-Mercaptopurine (6-MP) or Methotrexate (MTX); stable dosing for 8 weeks before randomization;
- Oral corticosteroid therapy (prednisone ≤ 20 mg/day or budesonide ≤ 9 mg/day); stable dosing for 2 weeks before randomization;
- Topical therapy (foams, clysms) with mesalazine or budesonide: stable dosing for 2 weeks before randomization.
- Complete vaccination against SARS-CoV-2 according to the recommendation of the "Ständige Impfkommission" (STIKO)
- 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.
- Potentially childbearing patient: negative pregnancy test and use of a highly effective contraceptive method
Exclusion Criteria:
- Crohn's disease or indeterminate colitis or proctitis ulcerosa alone
- Acute abdomen or other clinical emergencies (e.g. toxic megacolon, fulminant gastrointestinal hemorrhage, ileus, perforation, etc.)
- Previous operations on the colon: colectomy, partial colon resections
- current gastrointestinal infections
- Congenital or acquired immunodeficiency
- severe comorbidity (e.g. insulin-dependent diabetes mellitus, decompensated liver cirrhosis, primary sclerosing cholangitis, renal impairment > grade 2)
- diagnosis of a malignoma in the last 3 years
- refusal of endoscopies with video documentation
- No specific therapy for ulcerative colitis to date
- Previous treatment with TNF-, IL12/IL23-, or integrin-antibodies within the last 8 weeks before randomisation
- Treatment with calcineurin inhibitors within the last 4 weeks before randomization
- Treatment with JAK inhibitors (e.g., tofacitinib, filgotinib, or upadacitinib) within the last 4 weeks prior to randomization
- Systemic antibiotic treatment within the last 8 weeks prior to randomization.
- Known intolerance of metronidazole or vancomycin
- Previous FMT or FMFT, previous participation in this study (screening allowed)
- Participation in a clinical trial within the last 3 months
- Use of probiotics in tablet, capsule, or powder form, or appropriate drinking yogurts (or similar) within 2 weeks prior to randomization
- Failure to ensure frozen storage of investigational products
- Addictive or other medical conditions or circumstances that do not allow the subject to appreciate the nature, significance, scope, and possible consequences of the clinical trial
- Indications that the patient would be unlikely to comply with the protocol (e.g., unwillingness to cooperate - compliance questionable)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03843385
Contact: Andreas Stallmach, Prof. | +49-3641-9 ext 324401 | andreas.stallmach@med.uni-jena.de | |
Contact: Johannes Stallhofer, MD | +49-3641-9 ext 322303 | johannes.stallhofer@med.uni-jena.de |
Germany | |
Jena University Hospital | Recruiting |
Jena, Thuringia, Germany | |
Contact: Andreas Stallmach, Prof. +49 3641 32 44 01 andreas.stallmach@med.uni-jena.de | |
Sozialstiftung Bamberg | Recruiting |
Bamberg, Germany | |
Contact: Jost Langhorst, Prof. | |
Charité Berlin | Recruiting |
Berlin, Germany | |
Contact: Britta Siegmund, Prof. | |
DRK Kliniken Berlin Westend | Recruiting |
Berlin, Germany | |
Contact: Andreas Sturm, Prof. | |
Krankenhaus Waldfriede | Recruiting |
Berlin, Germany | |
Contact: Carsten Büning, Prof. | |
Städtisches Klinikum Braunschweig | Recruiting |
Braunschweig, Germany | |
Contact: Max Reinshagen, Prof. | |
Universitätsklinikum Carl Gustav Carus Dresden | Recruiting |
Dresden, Germany | |
Contact: Renate Schmelz, Dr. med. | |
FAU Universität Erlangen-Nürnberg | Recruiting |
Erlangen, Germany | |
Contact: Raja Atreya, Prof. | |
Agaplesion Markus Krankenhaus | Recruiting |
Frankfurt, Germany | |
Contact: Axel Dignaß, Prof. | |
Universitätsklinik Freiburg | Recruiting |
Freiburg, Germany | |
Contact: Peter Hasselblatt, Prof. | |
Klinikum Fulda | Recruiting |
Fulda, Germany | |
Contact: Carsten Schmidt, Prof. | |
Gesellschaft Klinische Studien Leipzig | Recruiting |
Leipzig, Germany | |
Contact: Nils Teich, Prof. | |
Universitätsklinikum Ulm | Recruiting |
Ulm, Germany | |
Contact: Jochen Klaus, Prof. |
Study Director: | Andreas Stallmach, Prof. | Jena University Hospital |
Responsible Party: | Tabitha Heller, Project manager, Jena University Hospital |
ClinicalTrials.gov Identifier: | NCT03843385 |
Other Study ID Numbers: |
KS2017-114 |
First Posted: | February 18, 2019 Key Record Dates |
Last Update Posted: | November 24, 2023 |
Last Verified: | November 2023 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
fecal transplantation multidonor fecal transplantation |
Colitis Colitis, Ulcerative Inflammatory Bowel Diseases Ulcer Gastroenteritis |
Gastrointestinal Diseases Digestive System Diseases Colonic Diseases Intestinal Diseases Pathologic Processes |