A Study to Evaluate the Effect of Fecal Transplant and Dietary Changes on Disease Activity in Patients With Crohn Disease on Advanced Therapies (BOOST-CD)

Efficacy of Microbiome Manipulation Strategies (Fecal Microbial Transplant or Crohns Disease Exclusion Diet or Both) With Advanced Therapies (BiOlOgics and Small Molecules) to Break the Therapeutic Ceiling in Active Crohns Disease (BOOST-CD): A Multicenter Double Blind Factorial Randomized Controlled Trial

Advanced therapies including biologics and small molecules target specific inflammatory pathways. IBD's multifactorial etiology means that blocking a single pathway may not be sufficient for all patients. Even when combination of advanced therapies are used, the incremental benefits often diminish, reflecting the therapeutic ceiling. Furthermore, safety concerns also limit the potential to push beyond this ceiling. Increasing the dose or adding more immunosuppressive agents can lead to a higher risk of infections, malignancies, and other adverse effects, making it impractical to continually intensify treatment. Understanding the therapeutic ceiling in IBD highlights the need for innovative approaches that go beyond current strategies. Given the diverse microbial and immunological landscapes in IBD combining fecal microbiota transplantation (FMT) and Crohn's Disease Exclusion Diet (CDED) with advanced therapies represents a promising approach to break the therapeutic ceiling in CD. This strategy leverages the complementary mechanisms of action of FMT/CDED and advance therapies, potentially offering a more comprehensive treatment modality that addresses the complex and multifactorial nature of IBD. FMT involves the transfer of gut microbiota from a healthy donor to a patient, aiming to restore a balanced microbial community in the intestines. This can help modulate the immune system and reduce inflammation, which are central to Crohn's disease pathology. This study seeks to provide evidence on whether addition of microbiota manipulation by FMT and CDED offers additional benefits when used alongside advance therapies in active CD. The findings from this RCT are expected to significantly enhance treatment strategies, ensuring that patients receive the most effective and appropriate care based on robust scientific evidence. This multi-center double blind placebo-controlled RCT will randomize patients in 1:1:1:1 ratio to FMT, CDED and advance therapy vs sham FMT with advance therapy and CDED vs FMT, Advance therapy and sham diet vs Advance therapy with sham FMT and sham diet for induction and maintenance of remission in patients of active Crohn's disease. Randomization will be held centrally to ensure concealment of allocation. Random numbers will be generated by computerized random number schedule (The RAND), and the randomization list and numbered packing of the intervention will be prepared by a person not involved in the study. Randomization will be performed using permuted blocks of 8. Both the patient and the investigator will be blinded to the intervention

Study Overview

• Status: Recruiting
• Conditions: Crohns Disease
• Intervention / Treatment: Other: Fecal Microbial Transplantation; Other: Crohns Disease Exclusion Diet; Other: Advanced therapy; Other: Sham Diet; Other: Sham transplantation

Detailed Description

This is a multicenter, double-blind, factorial randomized controlled trial (RCT) evaluating the efficacy of microbiome manipulation strategies in patients with active Crohn's Disease (CD) undergoing advanced therapy (biologics or small molecules). The study will be conducted across six clinical centers in India, with an additional center designated for microbiome analysis.

Randomization and Blinding:

Randomization: Centralized, computer-generated randomization using permuted blocks of 8, 12, and 16 to ensure equal distribution across intervention arms.

Stratification: Not more than 1/3rd patients should be biological therapy exposed

Blinding:

The blinded team includes patients and principal investigators. Endoscopists administering FMT/sham FMT and dietitians providing dietary counseling will be unblinded

Sham-Control Methods:

FMT Sham: Sterile clean water infusions via colonoscopy. Diet Sham: Dietary counseling without any modification

Intervention Arms:

Patients are randomized into one of four treatment groups:

FMT + CDED + Advanced Therapy (Group A) FMT + Sham Diet + Advanced Therapy (Group B) Sham FMT + CDED + Advanced Therapy (Group C) Sham FMT + Sham Diet + Advanced Therapy (Group D)

Fecal Microbiota Transplantation (FMT):

FMT Route: Administered via colonoscopy.

FMT Schedule:

Induction Phase: Weeks 0, 2, and 6. Maintenance Phase: Every 8 weeks (weeks 10, 18, 26, 34, 42) for responders.

Preparation:

Donor Selection: Multi-donor approach with prescreening FMT Processing: 50 g stool freshly prepared and instilled within 4 hours.

Delivery Locations:

Week 0 (Bowel Preparation): Right colon/terminal ileum. Weeks 2 and 6 (No Bowel Preparation): Left colon. Crohn's Disease Exclusion Diet (CDED)

Diet Structure:

Induction Phase (Weeks 0-6): Elimination of specific pro-inflammatory dietary components.

Maintenance Phase (Weeks 6-48): Gradual reintroduction of certain food groups. Monitoring: Adherence tracked using the IBD NutriCare app, diet recall logs, and DietCal software.

Sham Diet: Patients follow a standard healthy diet with general dietary counseling.

Assessments and Data Collection Baseline Assessments (Week 0) Clinical Data: Crohn's Disease Activity Index (CDAI), stool frequency, rectal bleeding, and symptom tracking.

Laboratory Tests:

Hemogram, renal/liver function tests, blood glucose. Inflammatory Markers: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fecal calprotectin (FCP).

Microbiome Analysis: Stool samples stored at -80°C for sequencing.

Endoscopic Evaluation:

Scoring: Simple Endoscopic Score for CD (SES-CD). Blinded Central Review: Videos assessed by two independent readers; discrepancies adjudicated by a third reader.

Histology: Biopsies analyzed using DCA score (Distribution Chronicity and Activity).

Follow-up Assessments

Visit Schedule:

Induction Phase: Weeks 2, 4, 6, and 10. Maintenance Phase: Every 8 weeks (weeks 18, 26, 34, 42, and 48). Clinical Assessments: CDAI, PRO2 symptom tracking, medication adherence checks. Endoscopy: Week 10 and Week 48; central scoring of videos. Diet Adherence: Assessed at weeks 2, 4, 6, and 10, then every 8 weeks. Microbiome Sampling: Stool samples collected at weeks 10 and 48. Safety Monitoring and Adverse Events

Adverse Event (AE) Classification:

CTCAE Grading (Grade 1-5) for treatment-related AEs. Serious Adverse Events (SAEs): Hospitalization, life-threatening events, or disability.

Safety Monitoring Plan:

Pre-procedural safety checks for each FMT session. Immediate post-FMT monitoring (48 hours). Late safety assessments (14 days post-FMT, then every visit). Unblinding Procedure: Allowed only for SAE management with DSMB approval. Data Management and Statistical Analysis

Electronic Data Capture (EDC):

Platform: REDCap database with tiered access permissions. Audit Trails: Secure logs of data entry and modification.

Dietary Data Processing:

IBD NutriCare app logs converted into macronutrient composition reports. Adherence scoring based on 80% compliance threshold.

Microbiome Data Processing:

Samples sequenced at IIIT-Delhi, analyzed for diversity indices and metabolic pathways.

Statistical Plan:

Primary Analysis: Intention-to-treat (ITT) and per-protocol (PP) analyses. Longitudinal Modeling: Mixed-effects models for repeated measures.

Effect Size Estimation:

Sample size: 168 patients (42 per arm).

• Study Type: Interventional
• Enrollment (Estimated): 168
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Prof Vineet Ahuja, DM Gastroenterology; Phone Number: +91-9810707170; Email: vineet.aiims@gmail.com
• Study Contact Backup: Name: Dr Himanshu Narang, DM Gasteroentrology; Phone Number: +91-8800316504; Email: h92narang@gmail.com

Study Locations

• India
  • Chandigarh, India
    • Not yet recruiting
    • Department of Gastroentrology, Postgraduate Institute of Medical Education and Research
    • Contact: Dr Vishal Sharma, DM Gasteroentrology; Phone Number: +91-8872813399; Email: docvishalsharma@gmail.com
    • Contact: Dr Vishal Sharma, DM Gastroenterology
  • Delhi
    • New Delhi, Delhi, India
      • Recruiting
      • Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences
      • Contact: Prof Vineet Ahuja, DM Gasteroentrology; Phone Number: +91-9810707170; Email: vineet.aiims@gmail.com
      • Contact: Dr Himanshu Narang, DM Gastroentrology; Phone Number: +91-8800316504; Email: h92narang@gmail.com
      • Contact: Prof Vineet Ahuja, DM Gastroenterology
      • Contact: Prof Govind Makharia, DM Gastroenterology
      • Contact: Dr Purva Mathur, MD Microbiology
      • Contact: Dr Prasenjit Das, MD Pathology
  • Kerala
    • Kochi, Kerala, India
      • Not yet recruiting
      • Department of Gastroenterology, Lisie Hospital
      • Contact: Dr Mathew Philip, DM Gastroenterology
      • Contact: Dr Kiran Josy, DM Gastroenterology
      • Contact: Dr Mathew Philip, DM Gastroenterology; Phone Number: +91-9846045469; Email: drmathewphilip@gmail.com
      • Contact: Dr Kiran Josy, DM Gastroenterology; Phone Number: +91-9745243939; Email: drkiranjosy@gmail.com
  • Maharashtra
    • Mumbai, Maharashtra, India
      • Not yet recruiting
      • Lokmanya Tilak Municipal General Hospital and Lokmanya Tilak Municipal Medical College, Sion
      • Contact: Dr Sanjay Chandnani, DM Gastroenterology
      • Contact: Dr Sanjay Chandnani, DM Gastroenterology; Phone Number: +91-9049708800; Email: sanjy.med@gmail.com
  • Punjab
    • Ludhiana, Punjab, India
      • Not yet recruiting
      • Department of Gastroenterology, Dayanand Medical College
      • Contact: Prof Ajit Sood, DM Gastroenterology
      • Contact: Dr Arshdeep Singh, DM Gastroenterology
      • Contact: Prof Ajit Sood, DM Gastroenterology; Phone Number: +91-9815400718; Email: ajitsood10@gmail.com
      • Contact: Dr Arshdeep Singh, DM Gastroenterology; Phone Number: +91-9815337764; Email: drarshdeepsingh@gmail.com
  • Uttar Pradesh
    • Varanasi, Uttar Pradesh, India
      • Not yet recruiting
      • Department of Gastroenterology, Institute of Medical Sciences
      • Contact: Dr Devesh Prakash Yadav, DM Gastroenterology
      • Contact: Dr Devesh Prakash Yadav, DM Gastroenterology; Phone Number: +91-8130856563; Email: devesh.thedoc@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients with active Crohn disease in whom FMT is feasible
2. Active Crohn's disease who are candidates for advanced therapy (steroid refractory, Immunomodulator intolerant or refractory and moderately severe disease at the time of inclusion) or patients who have an intolerance to or have lost response to advanced therapies must have had their last treatment at least five half-lives prior randomization.
3. Aged between 18-75 years
4. CDAI greater than 150 and/or SES-CD equal or greater than 6 (or equal or greater than 4 if isolated ileal disease)

Exclusion Criteria:

1. Patients in remission (CDAI less than 150)
2. Stricturing disease (non-passable stricture) in whom FMT is not feasible
3. Fistulising phenotype or Perianal fistula or abscess
4. Isolated L4 disease
5. Active TB or Sepsis
6. Pregnant or lactating women
7. Patients with co-morbidities like CAD/CLD/CKD
8. Previous surgery for CD
9. Declining consent or not willing for FMT or diet advice
10. Patients with current or recent history of clinically severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiac, or neurological disease.
11. Positive assay or stool culture for pathogens (ova and parasite examination, bacteria) or positive test for Clostridioides difficile toxin at screening#
12. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fecal microbiota transplantation(FMT) with Crohns disease exclusion diet (CDED) and advanced therapy; 1. FMT via colonoscopy at 0, 2 and 6 weeks (preceded by 3 days antibiotics, only before first procedure) followed by (if treatment responder) 8 weekly during maintenance till 42 weeks 2. Crohn disease exclusion diet(CDED) throughout the study 3. Advanced therapy as standard dose and schedule	Other: Fecal Microbial Transplantation; This will involve colonoscopic instillation of fecal transplant; Other: Crohns Disease Exclusion Diet; The modified diet plan will be given to each study participant; Other: Advanced therapy; Advanced therapy as standard dose and schedule
Experimental: Fecal microbiota transplantation (FMT) with sham diet and Advanced therapy; 1. FMT via colonoscopy at 0, 2 and 6 weeks (preceded by 3 days antibiotics, only before first procedure) followed by (if treatment responder) 8 weekly during maintenance till 42 weeks 2. Dietary counselling throughout the study 3. Advanced therapy as standard dose and schedule	Other: Fecal Microbial Transplantation; This will involve colonoscopic instillation of fecal transplant; Other: Advanced therapy; Advanced therapy as standard dose and schedule; Other: Sham Diet; Dietary counselling alone
Experimental: Sham FMT with Crohns disease exclusion diet (CDED) and advanced therapy; 1. Sham FMT with instillation of clean water at 0, 2 and 6 weeks (preceded by 3 days antibiotics, only before first procedure) followed by (if treatment responder) - 8- weekly during maintenance till 42 weeks 2. CDED throughout the study 3. Advanced therapy as standard dose and schedule	Other: Crohns Disease Exclusion Diet; The modified diet plan will be given to each study participant; Other: Advanced therapy; Advanced therapy as standard dose and schedule; Other: Sham transplantation; Sham transplantation will involve saline infusion via colonoscopy
Sham Comparator: Sham Diet with Sham FMT with advance therapy; 1.Sham FMT with instillation of clean water at 0, 2 and 6 weeks (preceded by 3 days antibiotics, only before first procedure) followed by (if treatment responder) - 8- weekly during maintenance till 42 weeks 2. Dietary counselling throughout the study 3. Advanced therapy as standard dose and schedule.	Other: Advanced therapy; Advanced therapy as standard dose and schedule; Other: Sham Diet; Dietary counselling alone; Other: Sham transplantation; Sham transplantation will involve saline infusion via colonoscopy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with clinical remission and endoscopic response at week 10	Proportion of patients with clinical remission (defined as CDAI less than 150) and endoscopic response( defined decline in SES-CD by greater than 50%)	10 weeks
Proportion of patients with clinical remission and endoscopic remission at week 10	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)	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with clinical response at Week 10	Proportion of patients with clinical response is defined as either CDAI decrease from baseline of at least 70 points or CDAI less than 150	10 weeks
Proportion of patients with PRO2 Remission at Week 10	Proportion of patients with PRO2 Remission which is defined as Abdominal pain subscore of not more than 1 (on a scale of 0-3) and liquid or very soft stool (Bristol stool scale type 6 or 7) frequency subscore of not more than 3 calculated as a mean of 7 day count	10 weeks
Proportion of patients with endoscopic response at Week 10	Proportion of patients with endoscopic response which is defined as 50% reduction from baseline on SES-CD	10 weeks
Fecal microbiome and metabolite signature between responders and non-responders at week 10	It involves combined analysis of the microorganisms (bacteria, viruses, fungi, etc.) and the small molecules (metabolites) present in a person's stool sample	10 weeks
Proportion of patients with biomarker remission at Week 10	Proportion of patients with biomarker remission which is defined as fecal calprotectin ≤150 mcg/g	10 weeks
Proportion of patients with adverse events at Week 10	Proportion of Patients Experiencing Adverse Events (will be assessed according to common criteria for adverse events (CTCEA))	10 weeks
Proportion of patients with clinical response at Week 48	Proportion of patients with clinical response is defined as either CDAI decrease from baseline of at least 70 points or CDAI less than 150	48 weeks
Proportion of patients with PRO2 remission at Week 48	Proportion of patients with PRO2 remission is defined as Abdominal pain subscore of not more than 1 (on a scale of 0-3) and liquid or very soft stool (Bristol stool scale type 6 or 7) frequency subscore of not more than 3 calculated as a mean of 7 day count	48 weeks
Proportion of patients with endoscopic response at Week 48	Proportion of patients with endoscopic response defined as 50% reduction from baseline on SES-CD	48 weeks
Proportion of patients with Endoscopic remission at Week 48 weeks	Proportion of patients with Endoscopic remission defined as a SES-CD score of 2 or less	48 weeks
Proportion of patients with corticosteroid-free clinical remission at Week 48	Proportion of patients with corticosteroid-free clinical remission is defined as the CDAI<150 with no exposure to steroids over the previous 8 weeks	48 weeks
Fecal microbiome and metabolite signature between responders and non-responders at Week 48	It involves combined analysis of the microorganisms (bacteria, viruses, fungi, etc.) and the small molecules (metabolites) present in a person's stool sample	48 weeks
Proportion of patients with biomarker remission at Week 48	Proportion of patients with biomarker remission which is defined as fecal calprotectin ≤150 mcg/g	48 weeks
Proportion of patients with adverse event at Week 48	Proportion of Patients Experiencing Adverse Events (will be assessed according to common criteria for adverse events (CTCEA))	48 weeks
Proportion of patients with adverse event at Week 6	Proportion of Patients Experiencing Adverse Events (will be assessed according to common criteria for adverse events (CTCEA))	6 weeks
Proportion of Patients Experiencing Adverse Events at Week 26	Proportion of Patients Experiencing Adverse Events (will be assessed according to common criteria for adverse events (CTCEA))	26 weeks

Collaborators and Investigators

• Sponsor: All India Institute of Medical Sciences, New Delhi
• Investigators: Principal Investigator: Prof Vineet Ahuja, DM Gastroenterology, Department of Gastroenterology, AIIMS, New Delhi

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2025
• Primary Completion (Estimated): March 15, 2027
• Study Completion (Estimated): March 15, 2028

Study Registration Dates

• First Submitted: March 3, 2025
• First Submitted That Met QC Criteria: March 17, 2025
• First Posted (Actual): March 24, 2025

Study Record Updates

• Last Update Posted (Actual): April 4, 2025
• Last Update Submitted That Met QC Criteria: April 1, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Randomized Controlled Trial; Crohns disease; Factorial Design; Fecal Microbial Transplantation; Advanced therapy; Crohns disease exclusion diet
• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: AIIMSA2988/03.01.2025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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