Crohn Disease, Fecal Microbiota Transplantation, Inflammatory Bowel Diseases, Microbiome
Conditions
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.
Interventions
DRUGAntibiotics
All patients will receive a one week course of antibiotic therapy.
DIETARY_SUPPLEMENTDietician designed diet
All patients will be recommended dietary modification 3 weeks prior to, and during, the study.
DRUGFMT
Anaerobically prepared stool. Dosing will vary according to mode of administration.
OTHERPlacebo
Placebo will contain food colourant, 0.9% normal saline and glycerol.
Sponsors
The Queen Elizabeth Hospital
BiomeBank Adelaide
The University of Queensland
Monash University
St Vincent's Hospital Melbourne
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Randomisation tables will be computer generated by an independent statistician. The indistinguishable aspect of the FMT syringes (colour, packaging) will ensure the blindness of both patients and physicians in charge.
Intervention model description
Prospective, two clinical center, parallel-arm, randomised, double-blind, placebo-controlled trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical response | Week 8 | CDAI decrease of ≥100 or CDAI\<150 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Clinical remission | Week 8 and week 52 or Week 16 and week 60 (for open FMT group) | CDAI \<150 |
| 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 |
| Time to outcomes | Duration of trial | Time taken to achieve clinical response or remission during induction and maintenance phases |
Countries
Australia
Contacts
Primary ContactAmy Wilson O'Brien
Backup ContactSasha Fehily, MD
Outcome results
None listed