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

Longterm Transfer of FRozen Encapsulated Multidonor Stool Filtrate or Encapsulated Multidonor Microbiome for Chronic Active Ulcerative COlitis

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.

Study Overview

• Status: Recruiting
• Conditions: Inflammatory Bowel Diseases; Ulcerative Colitis
• Intervention / Treatment: Drug: encapsulated faecal microbiota filtrate; Drug: encapsulated faecal microbiota; Drug: Placebo

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 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
• Enrollment (Estimated): 129
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Andreas Stallmach, Prof.; Phone Number: +4936419324401; Email: andreas.stallmach@med.uni-jena.de
• Study Contact Backup: Name: Kathleen Lange, MD; Phone Number: +4936419324641; Email: Kathleen.Lange@med.uni-jena.de

Study Locations

• Germany
  • Bamberg, Germany
    • Recruiting
    • Sozialstiftung Bamberg
    • Contact: Jost Langhorst, Prof.
  • Berlin, Germany
    • Recruiting
    • Charite Berlin
    • Contact: Britta Siegmund, Prof.
  • Berlin, Germany
    • Recruiting
    • DRK Kliniken Berlin Westend
    • Contact: Andreas Sturm, Prof.
  • Berlin, Germany
    • Recruiting
    • Krankenhaus Waldfriede
    • Contact: Carsten Büning, Prof.
  • Berlin, Germany
    • Recruiting
    • Havelhöhe
    • Contact: Markus Wispler, Dr. med.
  • Dresden, Germany
    • Recruiting
    • Universitätsklinikum Carl Gustav Carus Dresden
    • Contact: Renate Schmelz, Dr. med.
  • Erlangen, Germany
    • Recruiting
    • FAU Universität Erlangen-Nürnberg
    • Contact: Raja Atreya, Prof.
  • Frankfurt, Germany
    • Recruiting
    • Agaplesion Markus Krankenhaus
    • Contact: Axel Dignaß, Prof.
  • Freiburg im Breisgau, Germany
    • Recruiting
    • Universitätsklinik Freiburg
    • Contact: Peter Hasselblatt, Prof.
  • Fulda, Germany
    • Recruiting
    • Klinikum Fulda
    • Contact: Carsten Schmidt, Prof.
  • Halle, Germany
    • Recruiting
    • Universitätsklinikum Halle (Saale)
    • Contact: Jens Walldorf, PD. Dr. med.
  • Hamburg, Germany
    • Recruiting
    • Universitatsklinikum Hamburg-Eppendorf
    • Contact: Thorben Fründt, Dr. med.
  • Kiel, Germany
    • Recruiting
    • Universitatsklinikum Schleswig Holstein
    • Contact: Stefan Schreiber, Prof.
  • Leipzig, Germany
    • Recruiting
    • Gesellschaft Klinische Studien Leipzig
    • Contact: Nils Teich, Prof.
  • Ludwigshafen, Germany
    • Recruiting
    • St. Marien- und St. Annastiftskrankenhaus
    • Contact: Tanja Kühbacher, Prof.
  • Lüneburg, Germany
    • Recruiting
    • Städtisches Klinikum Lüneburg
    • Contact: Christian Maaser, Prof.
  • Magdeburg, Germany
    • Recruiting
    • Otto-von-Guericke-Universität - Medizinische Fakultät
    • Contact: Ulrike von Arnim, PD Dr.med.
  • München, Germany
    • Recruiting
    • LMU Klinikum München - Campus Großhadern
    • Contact: Helga Török, PD Dr.med.
  • Ulm, Germany
    • Recruiting
    • Universitatsklinikum Ulm
    • Contact: Jochen Klaus, Prof.
  • Thuringia
    • Jena, Thuringia, Germany
      • Recruiting
      • Jena University Hospital
      • Contact: Andreas Stallmach, Prof.; Phone Number: +49 3641 32 44 01; Email: andreas.stallmach@med.uni-jena.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.
• previous vaccination against SARS-CoV-2 or previous SARS-CoV-2 infection or positive serology
• 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
• Lack of immunity to SARS-CoV-2
• Previous treatment with TNF-, IL12/IL23-, 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
• Treatment with S1P receptor modulators (e.g. ozanimod, etrasimod) within the last 4 weeks before 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / 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 Names: 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 Names: 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 Names: Encapsulated sterile saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
clinical 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).	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	52 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)	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	12 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)	12 weeks
mucosal inflammation - measured through fecal calprotectin	mucosal inflammation in stool samples at week 0, 4, 8, 12, 24, 36, 52 post first transfer of FMFT or FMT	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	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	52 weeks
MAYO Total Score	Comparison of the MAYO total Score between the 3 Arms (FMFT, FMT and Placebo)	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	12 weeks
Safety - adverse events and severe adverse events	adverse events and severe adverse events in the different treatment arms will be recorded	52 weeks

Collaborators and Investigators

• Sponsor: Andreas Stallmach
• Collaborators: German Federal Ministry of Education and Research
• Investigators: Study Director: Andreas Stallmach, Prof., Jena University Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: February 14, 2019
• First Submitted That Met QC Criteria: February 14, 2019
• First Posted (Actual): February 18, 2019

Study Record Updates

• Last Update Posted (Actual): February 13, 2026
• Last Update Submitted That Met QC Criteria: February 11, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: fecal transplantation; multidonor fecal transplantation
• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Gastroenteritis; Colitis; Colitis, Ulcerative; Inflammatory Bowel Diseases; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: KS2017-114

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No