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

Last updated: March 31, 2025
Sponsor: All India Institute of Medical Sciences, New Delhi
Overall Status: Active - Recruiting

Phase

N/A

Condition

Ulcerative Colitis

Crohn's Disease

Bowel Dysfunction

Treatment

Sham transplantation

Advanced Therapy

Fecal Microbial Transplantation

Clinical Study ID

NCT06906445
AIIMSA2987/03.01.2025
EMDR/CARE/12/2023-0000572
  • Ages 18-75
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

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 bleedscore equal or greater than 1 and Endoscopic Mayo score equal or greater than 2documented within 3 months of randomization or mild symptoms with high inflammatoryburden or poor prognostic features).

  3. Any disease extent E1, E2 or E3. Patients with Proctitis will be limited to 25percent of the entire pool of patients.

  4. Patients with an inadequate response, loss of response, or intolerance toconventional therapies example, aminosalicylates, corticosteroids,immunosuppressants or advanced therapies including but not limited to anti TNF alphaagents, anti-integrins, anti IL 12 or IL 23 agents, anti IL 23 agents, JAKinhibitors, or S1P receptor modulators. The last administration of any suchtreatment must have occurred at least five half-lives prior to randomization.

  5. Confirmed diagnosis of UC. The diagnosis must be confirmed by endoscopic andhistologic 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 basalplasmacytosis, OR two sigmoidoscopies, at least 7 days apart showing evidence ofendoscopic activity

Exclusion

Exclusion Criteria:

  1. Hospitalization of exacerbation of UC requiring intravenous corticosteroids

  2. Patients already on biologics (anti-tumor necrosis factor inhibitors) or smallmolecules (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 orIHC and or tissue PCR) at screening. (The patients with positive assay will betreated appropriately and tests will be repeated. Those with negative assay andpersistent 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, infectiouscolitis, 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, oruncontrolled renal, hepatic, Hematological, gastrointestinal, metabolic, endocrine,pulmonary, cardiac, or neurological disease.

  10. Pregnant females

Study Design

Total Participants: 220
Treatment Group(s): 5
Primary Treatment: Sham transplantation
Phase:
Study Start date:
March 15, 2025
Estimated Completion Date:
March 15, 2028

Study Description

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

Connect with a study center

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

    New Delhi, Delhi VINEET AHUJA
    India

    Active - Recruiting

  • Department of Gastroenterology, Lisie Hospital

    Kochi, Kerala
    India

    Site Not Available

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

    Mumbai, Maharashtra
    India

    Site Not Available

  • Department of Gastroenterology, Dayanand Medical College

    Ludhiana, Punjab DR AJIT SOOD
    India

    Site Not Available

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

    Chandigarh, Punjab/Haryana
    India

    Site Not Available

  • Department of Gastroenterology, Institute of Medical Sciences

    Varanasi, Uttar Pradesh
    India

    Site Not Available

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