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

NCT ID: NCT06906445

Last Updated: 2025-04-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

220 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-03-15

Study Completion Date

2028-03-15

Brief Summary

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Ulcerative colitis (UC) is a chronic inflammatory disease of the colon characterized by superficial mucosal inflammation. Treatment aims to achieve and maintain remission, improve quality of life, and minimize complications. Advanced therapies, including biologics and small molecules, have significantly improved UC management by targeting specific inflammatory pathways. However, due to the multifactorial nature of UC-driven by genetic, environmental, and microbial factors-many patients do not achieve sustained remission, highlighting a therapeutic ceiling. Gut microbial dysbiosis and immune dysregulation are central to UC pathogenesis, with diet playing a critical role in influencing the gut microbiome. While biologics and small molecules have limitations, innovative approaches like combining fecal microbiota transplantation (FMT) and dietary interventions with advanced therapies show promise. FMT restores microbial balance, modulates immunity, and reduces inflammation, while dietary modifications, such as anti-inflammatory diets, enhance FMT efficacy by creating a favorable environment for donor microbiota engraftment. The present study is designed to evaluate the efficacy of three different microbiome manipulation strategies- FMT, AID and FMT + AID in combination with advanced therapies in patients with active UC in a 2X2 factorial trial design. Patients would be randomized into four different arms: FMT, AID, FMT+AID and placebo. The advanced therapies (biologics or small molecules) would be given in all four arms as standard therapy. With this design the trial would answer two important questions: a) efficacy of combination treatment with advanced therapies and microbiome manipulation strategies in active UC, and b) comparative efficacy of different microbiome manipulation strategies.

Detailed Description

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This study is a multicenter, randomized, factorial-design, double-blind, controlled trial investigating the effects of fecal microbiota transplantation (FMT) and dietary interventions in patients with mild to moderate, treatment-naïve, active inflammatory bowel disease. The trial is being conducted across multiple clinical centers, with a central microbiome analysis facility.

Randomization and Blinding:

Randomization: Centralized, computerized randomization is employed to ensure balanced treatment allocation. The permuted block method, along with stratification based on disease characteristics, ensures equal distribution across intervention arms Blinding: Patients, investigators collecting clinical data, and endoscopic video assessors are blinded to treatment allocation. The dietitian and endoscopist performing FMT (or sham FMT) are unblinded

Intervention Arms:

Participants are assigned to one of four treatment arms:

FMT + Anti-inflammatory Diet (AID) +Advanced therapy FMT + Sham Diet+ Advanced therapy Sham FMT + AID+ Advanced therapy Sham FMT + Sham Diet+ Advanced therapy FMT is administered via colonoscopy at 0, 2, and 6 weeks, with responders receiving maintenance doses every 8 weeks until week 48

Participant Timeline and Assessments:

Baseline Assessments: Clinical, laboratory, and endoscopic evaluations, including serological tests, inflammatory markers, and microbiome profiling.

Follow-up Schedule: Visits occur at Week 0, Week 6, Week 10, and then every 8 weeks until Week 48.

Endoscopic Monitoring: Colonoscopy is performed at baseline, Week 10, and Week 48. Centralized endoscopic video scoring ensures consistency

Data Collection and Management:

Paper CRF's and Electronic Data: The paper based CRF's will be filled first and then data will be entered into a REDCap software.

Dietary Monitoring: Participants will use the IBD NutriCare mobile application for diet tracking.

Microbiome Analysis: Fecal samples are processed and analyzed at a designated microbiome research center.

Safety Monitoring and Compliance:

Adverse Event Reporting: All safety events, including potential serious adverse events (SAEs), are logged and monitored by the Data and Safety Monitoring Board (DSMB).

Protocol Deviations: Documented and assessed for impact on trial integrity. Training and Quality Control: Regular site training ensures adherence to the protocol, and periodic audits maintain data quality

Conditions

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Ulcerative Colitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Fecal Microbiota Transplantation and Anti inflammatory diet and advanced therapy

1.Oral vancomycin 500 mg BD for 3 days before the first FMT 2.FMT via colonoscopy at 0, 2, and 6 weeks for induction of remission 3.FMT via colonoscopy every 8 weeks (week 10, 18, 26, 34, 42) for maintenance of remission, if the patient is responder to the induction therapy 4.If the patient is a non-responder or has treatment failure to induction, he/she will be withdrawn from the study. 5.Patients with secondary loss of response, in the maintenance phase, will be withdrawn from the study 6.AID for 48 weeks. 7.Advanced therapy as standard dose and schedule

Group Type EXPERIMENTAL

Fecal Microbial Transplantation

Intervention Type OTHER

This will involve colonoscopic instillation of fecal transplant

Anti-Inflammatory Diet

Intervention Type OTHER

The modified diet plan will be given to each study participant

Advanced Therapy

Intervention Type OTHER

Advanced therapy as standard dose and schedule

Fecal Microbiota Transplantation and sham diet/standard dietary counselling and advanced therapy

1.Oral vancomycin 500 mg BD for 3 days before the first FMT 2.FMT via colonoscopy at 0, 2, and 6 weeks for induction of remission 3.FMT via colonoscopy every 8 weeks (week 10, 18, 26, 34, 42) for maintenance of remission, if the patient is responder to the induction therapy 4.If the patient is a non-responder or has treatment failure to induction, he/she will be withdrawn from the study. 5.Patients with secondary loss of response, in the maintenance phase, will be withdrawn from the study 6. Sham AID/Standard dietary counseling for 48 weeks. 7. Advanced therapy as standard dose and schedule

Group Type EXPERIMENTAL

Fecal Microbial Transplantation

Intervention Type OTHER

This will involve colonoscopic instillation of fecal transplant

Sham Diet

Intervention Type OTHER

Dietary counselling alone

Advanced Therapy

Intervention Type OTHER

Advanced therapy as standard dose and schedule

Sham Transplantation and Anti inflammatory diet and advanced therapy

1.Oral placebo 1 BD for 3 days before first FMT 2.Sham FMT via colonoscopy (instillation of clean water) at 0, 2, and 6 weeks 3.Sham FMT via colonoscopy (instillation of clean water) every 8 weeks (week 10, 18, 26, 34, 42) for maintenance of remission, if the patient is responder to the induction therapy 4.If the patient is a non-responder or has treatment failure to induction therapy, he/she will be withdrawn from the study. 5.Patients with secondary loss of response, in the maintenance phase, will be withdrawn from the study 6. AID for 48 weeks. 7. Advanced therapy as standard dose and schedule.

Group Type EXPERIMENTAL

Anti-Inflammatory Diet

Intervention Type OTHER

The modified diet plan will be given to each study participant

Sham transplantation

Intervention Type OTHER

Sham FMT will involve saline infusion via colonoscopy

Advanced Therapy

Intervention Type OTHER

Advanced therapy as standard dose and schedule

Sham transplantation and Sham Diet and advanced therapy

1.Oral placebo 1 BD for 3 days before first FMT 2. Sham FMT via colonoscopy (instillation of clean water) at 0, 2, and 6 weeks 3. Sham FMT via colonoscopy (instillation of clean water) every 8 weeks (week 10, 18, 26, 34, 42) for maintenance of remission, if the patient is responder to the induction therapy 4. If the patient is a non-responder or has treatment failure to induction therapy, he/she will be withdrawn from the study. 5. Patients with secondary loss of response, in the maintenance phase, will be withdrawn from the study 6. Sham AID/Standard dietary counseling for 48 weeks 7. Advanced therapy as standard dose and schedule

Group Type SHAM_COMPARATOR

Sham transplantation

Intervention Type OTHER

Sham FMT will involve saline infusion via colonoscopy

Sham Diet

Intervention Type OTHER

Dietary counselling alone

Advanced Therapy

Intervention Type OTHER

Advanced therapy as standard dose and schedule

Interventions

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Fecal Microbial Transplantation

This will involve colonoscopic instillation of fecal transplant

Intervention Type OTHER

Anti-Inflammatory Diet

The modified diet plan will be given to each study participant

Intervention Type OTHER

Sham transplantation

Sham FMT will involve saline infusion via colonoscopy

Intervention Type OTHER

Sham Diet

Dietary counselling alone

Intervention Type OTHER

Advanced Therapy

Advanced therapy as standard dose and schedule

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. Adult (age 18 to 75 years) patients
2. Patients with active UC (defined as mMS equal or greater than 3 with rectal bleed score equal or greater than 1 and Endoscopic Mayo score equal or greater than 2 documented within 3 months of randomization or mild symptoms with high inflammatory burden or poor prognostic features).
3. Any disease extent E1, E2 or E3. Patients with Proctitis will be limited to 25 percent of the entire pool of patients.
4. Patients with an inadequate response, loss of response, or intolerance to conventional therapies example, aminosalicylates, corticosteroids, immunosuppressants or advanced therapies including but not limited to anti TNF alpha agents, anti-integrins, anti IL 12 or IL 23 agents, anti IL 23 agents, JAK inhibitors, or S1P receptor modulators. The last administration of any such treatment must have occurred at least five half-lives prior to randomization.
5. Confirmed diagnosis of UC. The diagnosis must be confirmed by endoscopic and histologic evidence and corroborated by a histopathology report
6. Subjects who are willing and able to comply with treatment plan, laboratory tests, daily bowel movement diary call and other study procedures
7. Subjects who are willing to provide a written informed consent for FMT
8. Agree to adhere to the diet schedule
9. Infective colitis ruled out Biopsy showing crypt architecture distortion or basal plasmacytosis, OR two sigmoidoscopies, at least 7 days apart showing evidence of endoscopic activity

Exclusion Criteria

1. Hospitalization of exacerbation of UC requiring intravenous corticosteroids
2. Patients already on biologics (anti-tumor necrosis factor inhibitors) or small molecules (tofacitinib) for equal or more than 2 weeks.
3. Clinical signs of fulminant colitis or toxic megacolon
4. Positive assay or stool culture for pathogens (ova and parasite examination, bacteria) or positive test for Clostridioides difficile toxin or CMV (histology or IHC and or tissue PCR) at screening. (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.)
5. Active or inadequately treated infections, including Mycobacterium tuberculosis.
6. Presence of IBD-unclassified, microscopic colitis, ischemic colitis, infectious colitis, or clinical findings suggestive of Crohn's Disease.
7. Patients infected with human immunodeficiency virus (HIV)
8. Patients with current or past history of malignancy.
9. Patients with current or recent history of clinically severe, progressive, or uncontrolled renal, hepatic, Hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiac, or neurological disease.
10. Pregnant females
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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All India Institute of Medical Sciences

OTHER

Sponsor Role lead

Responsible Party

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Prof. Vineet Ahuja

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Prof Vineet Ahuja, DM Gastroenterology

Role: PRINCIPAL_INVESTIGATOR

Department of Gastroenterology, AIIMS, New Delhi

Locations

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Department of Gastroenterology, Lisie Hospital

Kochi, Kerala, India

Site Status NOT_YET_RECRUITING

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

Mumbai, Maharashtra, India

Site Status NOT_YET_RECRUITING

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

New Delhi, National Capital Territory of Delhi, India

Site Status RECRUITING

Department of Gastroenterology, Dayanand Medical College

Ludhiana, Punjab, India

Site Status NOT_YET_RECRUITING

Department of Gastroentrology, Postgraduate Institute of Medical Education and Research,

Chandigarh, Punjab/Haryana, India

Site Status NOT_YET_RECRUITING

Department of Gastroenterology, Institute of Medical Sciences

Varanasi, Uttar Pradesh, India

Site Status NOT_YET_RECRUITING

Countries

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India

Central Contacts

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Prof Vineet Ahuja, DM Gastroenterology

Role: CONTACT

+91-9810707170

Dr Himanshu Narang, DM Gasteroentrology

Role: CONTACT

+91-8800316504

Facility Contacts

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Dr Mathew Philip, DM Gastroenterology

Role: primary

+91-9846045469

Dr Kiran Josy, DM Gastroenterology

Role: backup

+91-9745243939

Dr Sanjay Chandnani, DM Gastroenterology

Role: primary

+91-9049708800

Prof Vineet Ahuja, DM Gasteroentrology

Role: primary

+91-9810707170

Dr Himanshu Narang, DM Gastroentrology

Role: backup

+91-8800316504

Prof Ajit Sood, DM Gastroenterology

Role: primary

+91-9815400718

Dr Arshdeep Singh, DM Gastroenterology

Role: backup

+91-9815337764

Dr Vishal Sharma, DM Gastroenterology

Role: primary

+91-8872813399

Dr Devesh Prakash Yadav, DM Gastroenterology

Role: primary

+91-8130856563

Other Identifiers

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EMDR/CARE/12/2023-0000572

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

AIIMSA2987/03.01.2025

Identifier Type: -

Identifier Source: org_study_id

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