Restoration of the Microbiome Through Superdonor Selection

NCT03110289 | Unknown DMC

• 1 other identifier: S59525
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

The AIM of this study is to investigate whether the FMT success rate in active UC patients can be increased by intensive donor pre-screening, anaerobic preparation of the FMT and by repeated FMT. The investigators will start a national multi-centre double-blind randomized sham-controlled trial in April 2017 at 6 hospitals in Belgium and 2 in The Netherlands. They will randomly allocate 108 patients with active ulcerative colitis (Mayo score 4-10, endoscopic Mayo score 2 or 3) in a 1:1 ratio, using a pre-established randomization list, to either 'superdonor' faecal microbiota transplantation or autologous fecal microbiota transplantation (=sham). Each patient will receive 4 FMT's. At baseline FMT will be performed during sigmoidoscopy. At week 1, 2 and 3, the FMT will be administered through rectal instillation. Each FMT will be derived from one donor. Donors will be pre-selected based on a species richness and abundance of taxa of interest. The primary outcome will be steroid-free clinical and endoscopic remission at week 8 (Mayo score ≤2, all subscores ≤ 1, and ≥1 point reduction in endoscopy subscore). Fecal, blood and mucosal samples and questionnaires will be collected at different time points. 16S rRNA stool analysis will be performed to assess the microbial changes after FMT.

Conditions

Ulcerative Colitis

Keywords

Fecal microbiota transplantation

Outcome Measures

Primary Outcomes (2)

• steroid-free clinical remission

  defined as a total Mayo score of 2 or less and with all Mayo subscores of 1 or less.

  Week 8

• steroid-free endoscopic remission or response

  defined as at least a 1 point reduction from baseline in the endoscopy subscore.

  Week 8

Secondary Outcomes (5)

• the investigation of changes in blood and fecal inflammatory markers before and after FMT

  Week 8

• Steroid-free clinical remission

  Week 8

• Steroid-free clinical response

  Week 8

• Steroid-free endoscopic response

  Week 8

• Steroid-free endoscopic remission

  Week 8

Study Arms (2)

Superdonor FMT

EXPERIMENTAL

Fecal microbiota transplantation from a healthy donor that was selected based on a fecal/blood screening, medical interview and on abundance of taxa of the investigators their interest

Other: superdonor FMT

Autologous FMT

SHAM COMPARATOR

Fecal microbiota transplantation derived from feces from the patient her/himself.

Other: autologous FMT

Interventions

superdonor FMT OTHER

Fecal microbiota transplantation (FMT) is the transfer of feces from a healthy "superdonor" to the patient.

Superdonor FMT

autologous FMT OTHER

Fecal microbiota transplantation (FMT) with feces from the patient him/herself

Autologous FMT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>18 years
• Patients with currently mild-moderate active ulcerative colitis (defined by endoscopic Mayo sub score 2-3 and a Total Mayo score between 4-10)
• Provide written informed consent to participate as shown by a signature on the consent form.
• Patients on concomitant UC-therapy are allowed if the concomitant treatment is restricted to current treatment and at a stable dose (not in the induction faze).
• Topical therapy and trial medication is not allowed.
• A maximum dose of 15mg methylprednisolone.
• Negative coproculture (Salmonella, Shigella, Yersinia, Campylobacter, Entamoeba histoliytica, Clostridium difficile toxins and enteropathogenic E. coli)
• Women need to use reliable contraceptives during participation in the study

You may not qualify if:

• Consent not obtained or unable to give informed consent
• Condition leading to profound immunosuppression
• For example: HIV, infectious diseases leading to immunosuppression, bone marrow malignancies, liver cirrhosis
• Use of systemic chemotherapy
• Use of antibiotics in the previous 4 weeks
• Surgery: Total colectomy, presence of a stoma or ileo-anal pouch
• Presence of an intra-abdominal fistula
• Colon carcinoma
• Diverticulitis
• Patients who are steroid dependent and requiring \>15mg methyl prednisone 2 week before START.
• Detection of a gastrointestinal pathogen on stool analysis
• A diagnosis of Crohn's disease of indeterminate colitis
• Females who are pregnant or actively trying to fall pregnant

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead
• Fund for Scientific Research, Flanders, Belgium: collaborator

Study Sites (1)

UZ Leuven

Leuven, Vlaams Brabant, 3010, Belgium

RECRUITING

Related Publications (1)

• Caenepeel C, Deleu S, Vazquez Castellanos JF, Arnauts K, Braekeleire S, Machiels K, Baert F, Mana F, Pouillon L, Hindryckx P, Lobaton T, Louis E, Franchimont D, Verstockt B, Ferrante M, Sabino J, Vieira-Silva S, Falony G, Raes J, Vermeire S. Rigorous Donor Selection for Fecal Microbiota Transplantation in Active Ulcerative Colitis: Key Lessons From a Randomized Controlled Trial Halted for Futility. Clin Gastroenterol Hepatol. 2025 Mar;23(4):621-631.e7. doi: 10.1016/j.cgh.2024.05.017. Epub 2024 May 23.

  PMID: 38788915 DERIVED

MeSH Terms

Conditions

Colitis, Ulcerative

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Study Officials

• Séverine Vermeire, MD and PhD

  UZ Leuven

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clara Caenepeel, MD

CONTACT

+32 16 32 51 48; clara.caenepeel@kuleuven.be

Jolien Lefrère

CONTACT

+32 16 34 88 56; jolien.lefrere@uzleuven.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD-student under supervision of Prof. Dr. Séverine Vermeire

Model Details: We will randomly allocate 108 patients with active ulcerative colitis (Mayo score 4-10, endoscopic Mayo score 2 or 3) in a 1:1 ratio, using a pre-established randomization list, to either 'superdonor' faecal microbiota transplantation or autologous fecal microbiota transplantation (=sham)

Study Record Dates

• First Submitted: March 30, 2017
• First Posted: April 12, 2017
• Study Start: April 30, 2017
• Primary Completion: April 30, 2019
• Study Completion: April 30, 2019
• Last Updated: March 30, 2018

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)