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

NCT06890637 | Recruiting DMC

• 1 other identifier: AIIMSA2988/03.01.2025
• Study Type: interventional
• Target: 168
• Locations: 1 country
• Sites: 6

Brief Summary

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

Conditions

Crohns Disease

Keywords

Randomized Controlled Trial; Factorial Design; Fecal Microbial Transplantation; Crohns disease exclusion diet; Crohns disease; Advanced therapy

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (16)

• 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

Study Arms (4)

Fecal microbiota transplantation(FMT) with Crohns disease exclusion diet (CDED) and advanced therapy

EXPERIMENTAL

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; Other: Crohns Disease Exclusion Diet; Other: Advanced therapy

Fecal microbiota transplantation (FMT) with sham diet and Advanced therapy

EXPERIMENTAL

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; Other: Sham Diet; Other: Advanced therapy

Sham FMT with Crohns disease exclusion diet (CDED) and advanced therapy

EXPERIMENTAL

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; Other: Sham transplantation; Other: Advanced therapy

Sham Diet with Sham FMT with advance therapy

SHAM COMPARATOR

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: Sham transplantation; Other: Sham Diet; Other: Advanced therapy

Interventions

Fecal Microbial Transplantation OTHER

This will involve colonoscopic instillation of fecal transplant

Fecal microbiota transplantation (FMT) with sham diet and Advanced therapy; Fecal microbiota transplantation(FMT) with Crohns disease exclusion diet (CDED) and advanced therapy

Crohns Disease Exclusion Diet OTHER

The modified diet plan will be given to each study participant

Fecal microbiota transplantation(FMT) with Crohns disease exclusion diet (CDED) and advanced therapy; Sham FMT with Crohns disease exclusion diet (CDED) and advanced therapy

Sham transplantation OTHER

Sham transplantation will involve saline infusion via colonoscopy

Sham Diet with Sham FMT with advance therapy; Sham FMT with Crohns disease exclusion diet (CDED) and advanced therapy

Sham Diet OTHER

Dietary counselling alone

Fecal microbiota transplantation (FMT) with sham diet and Advanced therapy; Sham Diet with Sham FMT with advance therapy

Advanced therapy OTHER

Advanced therapy as standard dose and schedule

Fecal microbiota transplantation (FMT) with sham diet and Advanced therapy; Fecal microbiota transplantation(FMT) with Crohns disease exclusion diet (CDED) and advanced therapy; Sham Diet with Sham FMT with advance therapy; Sham FMT with Crohns disease exclusion diet (CDED) and advanced therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with active Crohn disease in whom FMT is feasible
• Aged between 18-75 years
• CDAI greater than 150 and/or SES-CD equal or greater than 6 (or equal or greater than 4 if isolated ileal disease)

You may not qualify if:

• Patients in remission (CDAI less than 150)
• Stricturing disease (non-passable stricture) in whom FMT is not feasible
• Fistulising phenotype or Perianal fistula or abscess
• Isolated L4 disease
• Active TB or Sepsis
• Pregnant or lactating women
• Patients with co-morbidities like CAD/CLD/CKD
• Previous surgery for CD
• Declining consent or not willing for FMT or diet advice
• 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

Sponsors & Collaborators

• All India Institute of Medical Sciences: lead

Study Sites (6)

Department of Gastroenterology, Lisie Hospital

Kochi, Kerala, India

NOT YET RECRUITING

Lokmanya Tilak Municipal General Hospital and Lokmanya Tilak Municipal Medical College, Sion

Mumbai, Maharashtra, India

NOT YET RECRUITING

Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences

New Delhi, National Capital Territory of Delhi, India

RECRUITING

Department of Gastroenterology, Dayanand Medical College

Ludhiana, Punjab, India

NOT YET RECRUITING

Department of Gastroenterology, Institute of Medical Sciences

Varanasi, Uttar Pradesh, India

NOT YET RECRUITING

Department of Gastroentrology, Postgraduate Institute of Medical Education and Research

Chandigarh, India

NOT YET RECRUITING

MeSH Terms

Conditions

Crohn Disease

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Officials

• Prof Vineet Ahuja, DM Gastroenterology

  Department of Gastroenterology, AIIMS, New Delhi

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Prof Vineet Ahuja, DM Gastroenterology

CONTACT

+91-9810707170; vineet.aiims@gmail.com

Dr Himanshu Narang, DM Gasteroentrology

CONTACT

+91-8800316504; h92narang@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 3, 2025
• First Posted: March 24, 2025
• Study Start: March 15, 2025
• Primary Completion (Estimated): March 15, 2027
• Study Completion (Estimated): March 15, 2028
• Last Updated: April 4, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

IN (6)