A Study to Evaluate the Effect of Fecal Transplant and Dietary Changes on Disease Activity in Patients With Newly Diagnosed Active Crohn Disease (ALTER-CD)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Crohn Disease
• Intervention / Treatment: Other: Fecal Microbial Transplantation; Other: Crohns disease exclusion diet; Other: Sham diet; Other: Sham transplantation

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:

Fecal Microbiota Transplantation (FMT)- Patients receive a 3-day course of oral vancomycin (500 mg BD) before the first FMT.

Freshly prepared 50 g stool is used for each FMT, and the transplant is administered within 4 hours of preparation.

FMT is delivered via colonoscopy at weeks 0, 2, and 6, followed by 8-weekly maintenance sessions for responders at weeks 10, 18, 26, 34, 42.

Multiple donors (n≥2) are used to ensure microbiome diversity. The first FMT session is instilled in the right colon/terminal ileum post bowel preparation, whereas maintenance sessions involve left-colon infusion without bowel preparation.

Crohn's Disease Exclusion Diet (CDED)- Patients assigned to CDED follow a phased dietary protocol designed to limit exposure to pro-inflammatory dietary components and enhance gut microbiome stability.

CDED consists of an induction and maintenance phase, with structured dietary charts and counseling provided by a dietitian.

Compliance is monitored via telephonic interviews and a dedicated diet tracking app (IBD NutriCare).

Sham Interventions- Sham FMT: Patients receive sterile water or saline infusions via colonoscopy at the same time points as FMT.

Sham Diet: Patients receive general dietary advice but do not follow the CDED protocol.

Randomization and Blinding- Central randomization is conducted using a secure web-based system (REDCap), utilizing stratified randomization based on disease extent.

The study follows a double-blind approach:

Blinded: Patients, clinical assessors, and endoscopic scorers. Unblinded: Endoscopists administering FMT/sham FMT and dietitians providing dietary counseling.

Oral vancomycin and placebo capsules are identically packed to maintain blinding.

Data Collection and Assessments- Baseline Assessments (Week 0) Clinical Assessment: Crohn's Disease Activity Index (CDAI), symptom scoring, and dietary adherence evaluation.

Laboratory Tests: Hemogram, renal/liver function, CRP, ESR, fecal calprotectin, and microbiome profiling.

Endoscopy: SES-CD scoring with high-definition endoscopic video recording. Histology: Biopsy samples are analyzed using Distribution Chronicity and Activity (DCA) scoring.

Follow-up Assessments- Clinical assessments at weeks 0, 2, 4, 6, 10, and every 8 weeks thereafter. Endoscopic assessments at baseline, week 10, and week 48, with central reading of all videos.

Fecal microbiome analysis at baseline, week 10, and week 48. Safety and Monitoring- Adverse Events (AEs) graded per CTCAE criteria (Grades 1-5). Serious Adverse Events (SAEs) include hospitalization, life-threatening conditions, or death.

DSMB reviews interim safety data at week 10 and 24. Emergency unblinding is permitted for critical medical decisions. Data Management- Data is collected using REDCap, with role-based access controls. Endoscopic images and videos are securely stored for centralized analysis. Microbiome sequencing data is processed at IIIT-Delhi. Statistical Considerations- Sample size calculation: 168 patients (42 per arm, 90% power).

Analysis Plan:

Intention-to-treat (ITT) and per-protocol (PP) analyses. Longitudinal mixed-effects modeling for microbiome shift

• 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
  • 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 Gasteroentrology; Phone Number: +91-9846045469; Email: drmathewphilip@gmail.com
      • Contact: Dr Kiran Josy, DM Gastroentrology; Phone Number: +91-9745243939; Email: drkiranjosy@gmail.com
      • Contact: Dr Mathew Philip, DM Gastroenterology
      • Contact: Dr Kiran Josy, DM Gastroenterology
  • Maharastra
    • Mumbai, Maharastra, India
      • Not yet recruiting
      • Lokmanya Tilak Municipal General Hospital and Lokmanya Tilak Municipal Medical College, Sion
      • Contact: Dr Sanjay Chandnani, DM Gasteroentrology; Phone Number: +91-9049708800; Email: sanjy.med@gmail.com
      • Contact: Dr Sanjay Chandnani, DM Gastroenterology
  • Punjab
    • Ludhiana, Punjab, India
      • Not yet recruiting
      • Department of Gastroenterology, Dayanand Medical College
      • Contact: Prof Ajit Sood, DM Gasteroentrology; Phone Number: +91-9815400718; Email: ajitsood10@gmail.com
      • Contact: Dr Arshdeep Singh, DM Gastroentrology; Phone Number: +91-9815337764; Email: drarshdeepsingh@gmail.com
      • Contact: Prof Ajit Sood, DM Gastroenterology
      • Contact: Dr Arshdeep Singh, DM Gastroenterology
  • Punjab/Haryana
    • Chandigarh, Punjab/Haryana, 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
  • Uttar Pradesh
    • Varanasi, Uttar Pradesh, India
      • Not yet recruiting
      • Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University
      • Contact: Dr Devesh Prakash Yadav, DM Gasteroentrology; Phone Number: +91-8130856563; Email: devesh.thedoc@gmail.com
      • Contact: Dr Devesh Prakash Yadav, DM Gastroenterology

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients with treatment-naive Crohns disease accessible with ileocolonoscopy
2. Symptom onset of less than 12 months

3. Mild to moderate disease activity with endoscopically active disease

   1. CDAI of greater than 150 and less than 450
   2. SES-CD of or equal to or greater than 6 (or equal to or greater than 4 if isolated ileal disease)
4. Aged between 18-75 years

Exclusion Criteria:

1. Patients with severe disease (CDAI greater than 450, SES-CD greater than 16) or requiring hospitalization
2. Patients who have been received on corticosteroids, immunosuppressants (azathioprine/ 6- mercaptoprine/methotrexate) for greater than 2 weeks
3. Biologicals or small molecule exposure
4. Stricturing (non-passable stricture), fistulising phenotype or perianal fistula/abscess
5. L4 disease
6. Pregnant or lactating women
7. Previous surgery for CD
8. Declining consent
9. Not willing for FMT/Dietary advise
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); 1. 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	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
Experimental: Fecal microbiota transplantation(FMT) and sham diet; 1. 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	Other: Fecal Microbial Transplantation; This will involve colonoscopic instillation of fecal transplant; Other: Sham diet; Dietary counselling alone
Experimental: Crohns Disease Exclusion Diet(CDED) and sham transplantation; 1. 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	Other: Crohns disease exclusion diet; The modified diet plan will be given to each study participant; Other: Sham transplantation; Sham FMT will involve saline infusion via colonoscopy
Sham Comparator: 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	Other: Sham diet; Dietary counselling alone; Other: Sham transplantation; Sham FMT 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 gretaer than 50%).	10 weeks
Proportion of patients with clinical remission and endoscopic remission at week 48	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
• Collaborators: Indian Council of Medical Research; Lokmanya Tilak Municipal Medical College and Hospital; Dayanand Medical College and Hospital; Post Graduate Institute of Medical Education and Research, Chandigarh; Institute of Medical Sciences of the Banaras Hindu University (BHU),India; Indraprastha Institute of Information Technology Delhi; Lisie Hospital
• 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; Crohn disease; Fecal microbiota transplantation; factorial design; Crohn disease exclusion diet
• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: AIIMSA2989/03.01.2025; EMDR/CARE/12/2023-0000572 (Other Grant/Funding Number: Indian Council of Medical Research)

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