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

NCT06906445 | Recruiting DMC

• 2 other identifiers: AIIMSA2987/03.01.2025EMDR/CARE/12/2023-0000572
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Ulcerative Colitis

Keywords

Randomized Controlled Trial; Fecal Microbial Transplantation; Anti-inflammatory diet; Factorial design; Ulcerative colitis; Advanced therapy

Outcome Measures

Primary Outcomes (2)

• Proportion of Patients Achieving Clinical Remission and Endoscopic Response at 10 weeks

  Proportion of patients having- 1. Clinical remission which is defined as the Modified Mayo Score (mMS) \< 2 \\ mMS- Full Title: Modified Mayo Score Range: 0 to 12 Higher Scores = Worse Outcome (A score of 0 represents no disease activity, and a score of 12 represents the most severe disease activity.) 2. Endoscopic response which is defined as Mayo Endoscopic Score (MES) by 1 point MES- Full Title: Mayo Endoscopic Score Range: 0 to 4 Higher Scores = Worse Outcome (A score of 0 represents normal endoscopic findings, and a score of 4 represents severe mucosal damage.

  10 weeks

• Proportion of patients having clinical remission and endoscopic remission at week 48

  Proportion of patients having- 1. Clinical remission which is defined as the Modified Mayo Score (mMS) \< 2 mMS- Full Title: Modified Mayo Score Range: 0 to 12 Higher Scores = Worse Outcome (A score of 0 represents no disease activity, and a score of 12 represents the most severe disease activity.) 2. Endoscopic response which is defined as Mayo Endoscopic Score (MES) by 1 point MES- Full Title: Mayo Endoscopic Score Range: 0 to 4 Higher Scores = Worse Outcome (A score of 0 represents normal endoscopic findings, and a score of 4 represents severe mucosal damage.

  48 weeks

Secondary Outcomes (24)

• Proportion of patients having clinical response at week 10

  10 weeks

• Proportion of patients having clinical remission at week 10

  10 weeks

• Proportion of Patients achieving Symptomatic Response at Week 10

  10 weeks

• Proportion of Patients achieving Symptomatic Remission at week 10

  10 weeks

• Proportion of Patients Achieving Endoscopic Response at Week 10

  10 weeks

Study Arms (4)

Fecal Microbiota Transplantation and Anti inflammatory diet and advanced therapy

EXPERIMENTAL

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

Other: Fecal Microbial Transplantation; Other: Anti-Inflammatory Diet; Other: Advanced Therapy

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

EXPERIMENTAL

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

Other: Fecal Microbial Transplantation; Other: Sham Diet; Other: Advanced Therapy

Sham Transplantation and Anti inflammatory diet and advanced therapy

EXPERIMENTAL

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.

Other: Anti-Inflammatory Diet; Other: Sham transplantation; Other: Advanced Therapy

Sham transplantation and Sham Diet and advanced therapy

SHAM COMPARATOR

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

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

Anti-Inflammatory Diet OTHER

The modified diet plan will be given to each study participant

Fecal Microbiota Transplantation and Anti inflammatory diet and advanced therapy; Sham Transplantation and Anti inflammatory diet and advanced therapy

Sham transplantation OTHER

Sham FMT will involve saline infusion via colonoscopy

Sham Transplantation and Anti inflammatory diet and advanced therapy; Sham transplantation and Sham Diet and advanced therapy

Sham Diet OTHER

Dietary counselling alone

Fecal Microbiota Transplantation and sham diet/standard dietary counselling and advanced therapy; Sham transplantation and Sham Diet and advanced therapy

Advanced Therapy OTHER

Advanced therapy as standard dose and schedule

Fecal Microbiota Transplantation and Anti inflammatory diet and advanced therapy; Fecal Microbiota Transplantation and sham diet/standard dietary counselling and advanced therapy; Sham Transplantation and Anti inflammatory diet and advanced therapy; Sham transplantation and Sham Diet 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:

• Adult (age 18 to 75 years) patients
• 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).
• Any disease extent E1, E2 or E3. Patients with Proctitis will be limited to 25 percent of the entire pool of patients.
• 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.
• Confirmed diagnosis of UC. The diagnosis must be confirmed by endoscopic and histologic evidence and corroborated by a histopathology report
• Subjects who are willing and able to comply with treatment plan, laboratory tests, daily bowel movement diary call and other study procedures
• Subjects who are willing to provide a written informed consent for FMT
• Agree to adhere to the diet schedule
• 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

You may not qualify if:

• Hospitalization of exacerbation of UC requiring intravenous corticosteroids
• Patients already on biologics (anti-tumor necrosis factor inhibitors) or small molecules (tofacitinib) for equal or more than 2 weeks.
• Clinical signs of fulminant colitis or toxic megacolon
• 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.)
• Active or inadequately treated infections, including Mycobacterium tuberculosis.
• Presence of IBD-unclassified, microscopic colitis, ischemic colitis, infectious colitis, or clinical findings suggestive of Crohn's Disease.
• Patients infected with human immunodeficiency virus (HIV)
• Patients with current or past history of malignancy.
• Patients with current or recent history of clinically severe, progressive, or uncontrolled renal, hepatic, Hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiac, or neurological disease.
• Pregnant females

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, VINEET AHUJA, India

RECRUITING

Department of Gastroenterology, Dayanand Medical College

Ludhiana, Punjab, DR AJIT SOOD, India

NOT YET RECRUITING

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

Chandigarh, Punjab/Haryana, India

NOT YET RECRUITING

Department of Gastroenterology, Institute of Medical Sciences

Varanasi, Uttar Pradesh, India

NOT YET RECRUITING

MeSH Terms

Conditions

Colitis, Ulcerative

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic 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: April 2, 2025
• Study Start: March 15, 2025
• Primary Completion (Estimated): March 15, 2027
• Study Completion (Estimated): March 15, 2028
• Last Updated: April 2, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

IN (6)