Microbial Restoration in Inflammatory Bowel Diseases

Phase 1

Recruiting

• Conditions: Fecal Microbiota Transplantation; Microbiome; Inflammatory Bowel Diseases; Crohn Disease
• Interventions: Drug: Antibiotics; Dietary Supplement: Dietician designed diet; Drug: FMT; Other: Placebo

• Registration Number: NCT04970446
• Lead Sponsor: St Vincent's Hospital Melbourne

Brief Summary

This is a prospective, two-centre, double-blind, parallel-arm, randomised, placebo-controlled trial evaluating the impact of FMT on patients with active Crohn's disease.

Detailed Description

The study will be conducted in two parts. The first part will involve all patients undergoing an optimisation phase, followed by randomisation into either intervention or placebo arms of the induction phase of the study. For patients achieving a pre-determined clinical response threshold at week 8 they will be re-randomised into the maintenance phase of the trial for a further 44 weeks.

FMT will be anaerobically prepared, freeze-thawed for administration.

Study Timeline

• Study First Submitted: 2021-07-18
• Study First Submitted QC: 2021-07-18
• Study First Posted: 2021-07-21
• Study Start: 2022-05-01
• Status Verified: 2025-01
• Last Update Submitted: 2025-02-23
• Last Update Posted: 2025-02-26
• Primary Completion: 2025-04-01
• Study Completion: 2026-04-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

Active Crohn's disease

• Confirmed endoscopic active inflammation (unless isolated small bowel disease that is inaccessible by endoscopy in which case sonographic inflammation is sufficient) within 6 months of study entry AND

• CDAI score of 220-450 AND

• One of the following:

  • CRP ≥5mg/L
  • faecal calprotectin ≥100μg/g
  • inflammation on imaging (either intestinal ultrasound or magnetic resonance imaging)

• Willing and able to attend the study sites for regular endoscopic procedures.

Exclusion Criteria

Active perianal or fistulising disease; Pregnant or intending to become pregnant within 12 months; Enteropathy or colitis other than Crohn's disease; Symptomatic intestinal stricture likely to require surgical treatment; Presence of a stoma; Presence of an ileoanal pouch; Total white cell count less than 3.0 x 109/L; Albumin less than 20g/L; Immunodeficiency (beyond that caused by immune suppressants used for the treatment of IBD) e.g. HIV or Common variable immune deficiency; Anaphylaxis/severe allergy to food; Thiopurine, methotrexate, biologic agent or small molecule inhibitors or aminosalicylates whose dose has been modified within the past two months, 1 month and two weeks of study entry, respectively; Prebiotic, probiotic or antibiotic therapy, or over-the-counter supplements therapy in the two weeks prior to study entry; Rectal topical Crohn's disease therapy in the 2 weeks prior to study entry; Prednisolone dose >20mg or budesonide dose >6mg; Unwilling or unable to taper corticosteroids to zero within 8 weeks of initial FMT; Active gastrointestinal infection; Alcohol consumption of a dependent nature; Primary sclerosing cholangitis; Any condition that the treating gastroenterologist deems to pose a theoretical risk to the patient undertaking FMT; Any patient that the treating clinicians feel is incapable of participating in the safe use of FMT.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
FMT arm	Dietician designed diet	Anaerobically prepared, freeze-thawed faecal microbiota transplantation
FMT arm	FMT	Anaerobically prepared, freeze-thawed faecal microbiota transplantation
Placebo arm	Antibiotics	Placebo liquid formulation (normal saline, glycerol, food colorant)
Placebo arm	Dietician designed diet	Placebo liquid formulation (normal saline, glycerol, food colorant)
Placebo arm	Placebo	Placebo liquid formulation (normal saline, glycerol, food colorant)
FMT arm	Antibiotics	Anaerobically prepared, freeze-thawed faecal microbiota transplantation

Primary Outcome Measures

Name	Time	Method
Clinical response	Week 8	CDAI decrease of ≥100 or CDAI\<150

Secondary Outcome Measures

Name	Time	Method
Clinical remission	Week 8 and week 52 or Week 16 and week 60 (for open FMT group)	CDAI \<150
Endoscopic response	Week 8 and 52 or Week 16 and 60	SES-CD reduction by 25% and 50%
Endoscopic remission	Week 8 and week 52 Week 16 and 60	SES-CD ≤2 or absence of ulcers
Histological Remission	Week 8 and 52 or Week 16 and 60	The absence of ulcers; the absence of acute inflammation histologically; one of either Geboes Score or Robarts Histology Index
Radiological remission	Week 8 and 52 or Week 16 and 60	IUS (BWT \<3mm and/or Limberg 0 or 1) or MRI (Wall thickness \<4mm and no or minimal wall enhancement)
Biochemical response	Week 8 and 52 or Week 16 and 60	Normalisation of CRP and faecal calprotectin (\<50ug/g, \<100ug/g, \<150ug/g, \<200ug/g, \<250ug/g
Time to outcomes	Duration of trial	Time taken to achieve clinical response or remission during induction and maintenance phases
Maintenance of clinical remission	Weeks 52 or 60	CDAI \<150
Sustained clinical remission	Weeks 52 or 60	CDAI \<150
Steroid-free clinical remission	Weeks 52 or 60	Steroid-free clinical remission
Safety outcomes	Duration of trial	Adverse events
Scientific outcomes	Week 8 and 52 or Week 16 and 60	Comparison of genetic, microbiological, metabolic and immunologic factors in the responders with the non-responders

Trial Locations

Locations (1)

St Vincents Hospital; 🇦🇺 Melbourne, Victoria, Australia