Efficacy of Microbiome Manipulation Strategies (fecAL Microbial Transplantation OR CDED OR Both) in Combination Standard Medical Therapy for Induction and Maintenance of Remission in Mild to Moderate tReatment naÃive Active Crohns Disease (ALTER-CD): a Multicentre Double-blind Factorial Randomized Controlled Trial
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Enrollment
- 168
- Locations
- 6
- Primary Endpoint
- Proportion of patients with clinical remission and endoscopic response at week 10
Study Overview
Brief Summary
Dysbiosis can be rectified by several methods: antibiotics, prebiotics, probiotics, dietary modulation, and fecal microbiota transplantation. There has been limited success with the isolated use of antibiotics and pre/probiotics in the treatment of IBD. Among the measures of dietary manipulation, the use of exclusive enteral nutrition (EEN) has shown superior, or at least equivalent, efficacy compared with steroids in pediatric CD. Although the results in adults are not as encouraging, recent cohort studies in patients with complicated CD have shown good success rates. Definite exclusion diets that exclude pro-inflammatory dietary constituents have also been tested with good clinical efficacy in patients with CD, who even failed treatment with anti-TNF agents. Various dietary approaches, inclusive of exclusive enteral nutrition, partial enteral nutrition, and Crohn's disease exclusion diet have been reported to be of benefit and are associated with changes in gut microbiome. Fecal microbiota transplantation (FMT) defined as the infusion of fecal suspension from a healthy individual into the gastrointestinal tract of an individual with GI disease carries a diverse population of microbiota and their metabolites and has been tested with varying efficacy in IBD. In general, FMT has shown good success rates in randomized control trials in patients with UC who failed conventional agents. Although limited small RCTs exist in CD, cohort studies have also shown good success rates. Therefore, the use of FMT in addition to standard medical therapy, is a concept that has not been previously explored and forms the basis for the present study. Therefore, a well-powered RCT is required to resolve the role of FMT in CD. In this study, patients will be recruited in four arms. Group A includes FMT+CDED+SMT, in Group B FMT+SMT+SHAM DIET, in Group C Sham FMT+CDED+SMT, in Group D Sham FMT+ Sham Diet+ SMT given. 168 patients will be recruited across 6 centers for around 3 years. Follow-up of the patient will be done at 0,2,6 and 10 weeks and 8 weekly up to 48 weeks.
Detailed Description
This study is a multi-center, double-blind, factorial randomized controlled trial designed to evaluate the efficacy of microbiome manipulation strategies using fecal microbiota transplantation (FMT), Crohn's Disease Exclusion Diet (CDED), or their combination in treatment-naïve patients with mild to moderate active Crohn's Disease (CD).
Study Setting
The trial is conducted at six FMT centers across India, with one additional center dedicated to microbiome analysis:
AIIMS, New Delhi, India Dayanand Medical College, Ludhiana, India PGIMER, Chandigarh, India Lisie Hospital, Kochi, India IMS, BHU, Varanasi, India Sion Hospital, Mumbai, India IIIT-Delhi, India(for microbiome analysis)
Intervention Details:
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Factorial
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients with treatment-naive Crohns disease accessible with ileocolonoscopy
- •Symptom onset of less than 12 months
- •Mild to moderate disease activity with endoscopically active disease
- •CDAI of greater than 150 and less than 450
- •SES-CD of or equal to or greater than 6 (or equal to or greater than 4 if isolated ileal disease)
- •Aged between 18-75 years
Exclusion Criteria
- •Patients with severe disease (CDAI greater than 450, SES-CD greater than 16) or requiring hospitalization
- •Patients who have been received on corticosteroids, immunosuppressants (azathioprine/ 6- mercaptoprine/methotrexate) for greater than 2 weeks
- •Biologicals or small molecule exposure
- •Stricturing (non-passable stricture), fistulising phenotype or perianal fistula/abscess
- •Pregnant or lactating women
- •Previous surgery for CD
- •Declining consent
- •Not willing for FMT/Dietary advise
- •Patients with current or recent history of clinically severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiac, or neurological disease.
- •Positive assay or stool culture for pathogens (ova and parasite examination, bacteria) or positive test for Clostridioides difficile toxin at screening#
- •Patients infected with human immunodeficiency virus (HIV) # The patients with positive assay will be treated appropriately and tests will be repeated. Those with negative assay and persistent activity will be included in the study.
Arms & Interventions
Crohns Disease Exclusion Diet(CDED) and sham transplantation
- Oral placebo 1 BD for 3 days before first FMT 2. Sham transplantation (clean water) via colonoscopy at 0, 2 and 6 weeks followed by (if treatment responder) 8 weekly during maintenance between 10 to 48 weeks 3.Crohns Disease Exclusion Diet for 48 weeks
Intervention: Crohns disease exclusion diet (Other)
Fecal Microbiota Transplantation(FMT) with Crohns disease exclusion diet(CDED)
- Oral vancomycin 500 mg BD for 3 days before first FMT 2. FMT via colonoscopy at 0, 2 and 6 weeks followed by (if treatment responder) 8 weekly during maintenance between 10 to 48 weeks
Intervention: Fecal Microbial Transplantation (Other)
Fecal Microbiota Transplantation(FMT) with Crohns disease exclusion diet(CDED)
- Oral vancomycin 500 mg BD for 3 days before first FMT 2. FMT via colonoscopy at 0, 2 and 6 weeks followed by (if treatment responder) 8 weekly during maintenance between 10 to 48 weeks
Intervention: Crohns disease exclusion diet (Other)
Fecal microbiota transplantation(FMT) and sham diet
- Oral vancomycin 500 mg BD for 3 days before first FMT 2. FMT via colonoscopy at 0, 2 and 6 weeks followed by (if treatment responder) 10 weeks and then 8 weekly during maintenance between 10 to 42 weeks 3. Diet counselling for 48 weeks
Intervention: Fecal Microbial Transplantation (Other)
Fecal microbiota transplantation(FMT) and sham diet
- Oral vancomycin 500 mg BD for 3 days before first FMT 2. FMT via colonoscopy at 0, 2 and 6 weeks followed by (if treatment responder) 10 weeks and then 8 weekly during maintenance between 10 to 42 weeks 3. Diet counselling for 48 weeks
Intervention: Sham diet (Other)
Crohns Disease Exclusion Diet(CDED) and sham transplantation
- Oral placebo 1 BD for 3 days before first FMT 2. Sham transplantation (clean water) via colonoscopy at 0, 2 and 6 weeks followed by (if treatment responder) 8 weekly during maintenance between 10 to 48 weeks 3.Crohns Disease Exclusion Diet for 48 weeks
Intervention: Sham transplantation (Other)
Sham transplantation with Sham diet
1.Oral placebo 1 BD for 3 days before first sham transplantation 2. Sham colonoscopy with instillation of saline at 0, 2, and 6 weeks followed by (if treatment responder) - 8-weekly during maintenance between 10 to 48 weeks
Intervention: Sham transplantation (Other)
Sham transplantation with Sham diet
1.Oral placebo 1 BD for 3 days before first sham transplantation 2. Sham colonoscopy with instillation of saline at 0, 2, and 6 weeks followed by (if treatment responder) - 8-weekly during maintenance between 10 to 48 weeks
Intervention: Sham diet (Other)
Outcomes
Primary Outcomes
Proportion of patients with clinical remission and endoscopic response at week 10
Time Frame: 10 weeks
Proportion of patients with clinical remission (defined as CDAI less than 150) and endoscopic response( defined decline in SES-CD by gretaer than 50%).
Proportion of patients with clinical remission and endoscopic remission at week 48
Time Frame: 48 weeks
Proportion of patients with clinical remission (defined as Crohn's disease activity index less than 150) and endoscopic remission (defined as Simple Endoscopic Score for Crohn's disease patients less than 3)
Secondary Outcomes
- Proportion of patients with clinical response at Week 10(10 weeks)
- Proportion of patients with PRO2 Remission at Week 10(10 weeks)
- Proportion of patients with endoscopic response at Week 10(10 weeks)
- Fecal microbiome and metabolite signature between responders and non-responders at week 10(10 weeks)
- Proportion of patients with biomarker remission at Week 10(10 weeks)
- Proportion of patients with adverse events at Week 10(10 weeks)
- Proportion of patients with clinical response at Week 48(48 weeks)
- Proportion of patients with Endoscopic remission at Week 48 weeks(48 weeks)
- Proportion of Patients Experiencing Adverse Events at Week 26(26 weeks)
- Proportion of patients with PRO2 remission at Week 48(48 weeks)
- Fecal microbiome and metabolite signature between responders and non-responders at Week 48(48 weeks)
- Proportion of patients with endoscopic response at Week 48(48 weeks)
- Proportion of patients with corticosteroid-free clinical remission at Week 48(48 weeks)
- Proportion of patients with biomarker remission at Week 48(48 weeks)
- Proportion of patients with adverse event at Week 48(48 weeks)
- Proportion of patients with adverse event at Week 6(6 weeks)
Investigators
Prof. Vineet Ahuja
Professor
All India Institute of Medical Sciences, New Delhi