Microbial Restoration in Inflammatory Bowel Diseases (MIRO II)

The MIRO II Study: Microbial Restoration in Inflammatory Bowel Diseases

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.

Study Overview

• Status: Recruiting
• Conditions: Inflammatory Bowel Diseases; Crohn Disease; Microbiome; Fecal Microbiota Transplantation
• Intervention / Treatment: Drug: Antibiotics; Dietary supplement: Dietician designed diet; Drug: FMT; Other: Placebo

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 Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Sasha Fehily, MD
• Study Contact Backup: Name: Amy Wilson O'Brien; Phone Number: 0392311352; Email: amy.wilson-obrien@svha.org.au

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Recruiting
      • St Vincents Hospital
      • Contact: Sasha Fehily; Email: miro.study@svha.org.au

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: FMT arm; Anaerobically prepared, freeze-thawed faecal microbiota transplantation	Drug: Antibiotics; All patients will receive a one week course of antibiotic therapy.; Dietary supplement: Dietician designed diet; All patients will be recommended dietary modification 3 weeks prior to, and during, the study.; Drug: FMT; Anaerobically prepared stool. Dosing will vary according to mode of administration.
Placebo Comparator: Placebo arm; Placebo liquid formulation (normal saline, glycerol, food colorant)	Drug: Antibiotics; All patients will receive a one week course of antibiotic therapy.; Dietary supplement: Dietician designed diet; All patients will be recommended dietary modification 3 weeks prior to, and during, the study.; Other: Placebo; Placebo will contain food colourant, 0.9% normal saline and glycerol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical response	CDAI decrease of ≥100 or CDAI<150	Week 8

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: St Vincent's Hospital Melbourne
• Collaborators: Monash University; The Queen Elizabeth Hospital; The University of Queensland; BiomeBank Adelaide
• Investigators: Principal Investigator: Michael A Kamm, MD, St Vincents Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2022
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: July 18, 2021
• First Submitted That Met QC Criteria: July 18, 2021
• First Posted (Actual): July 21, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 23, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Crohn Disease; Intestinal Diseases; Inflammatory Bowel Diseases; Anti-Infective Agents; Anti-Bacterial Agents
• Other Study ID Numbers: StvincentsmelbourneMIROII

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: When data becomes available
• IPD Sharing Access Criteria: TBC
• IPD Sharing Supporting Information Type: SAP

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