RECRUITINGINTERVENTIONAL

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

Efficacy of Microbiome Manipulation Strategies Fecal Microbial Transplant or Anti-inflammatory Diet or Both With Advanced Therapies BiOlOgics and Small Molecules to Break the Therapeutic Ceiling in Active Ulcerative Colitis BOOST-UC A Multicenter Double Blind Factorial Randomized Controlled Trial

About This Trial

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.

Who May Be Eligible (Plain English)

Who May Qualify: 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 willing to sign a consent form 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 Who Should NOT Join This Trial: 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 ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language

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

Treatments Being Tested

OTHER

Fecal Microbial Transplantation

This will involve colonoscopic instillation of fecal transplant

OTHER

Anti-Inflammatory Diet

The modified diet plan will be given to each study participant

OTHER

Sham transplantation

Sham FMT will involve saline infusion via colonoscopy

OTHER

Sham Diet

Dietary counselling alone

OTHER

Advanced Therapy

Advanced therapy as standard dose and schedule

Locations (6)

Department of Gastroenterology, Lisie Hospital

Kochi, Kerala, India

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

Mumbai, Maharashtra, India

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

New Delhi, National Capital Territory of Delhi, India

Department of Gastroenterology, Dayanand Medical College

Ludhiana, Punjab, India

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

Chandigarh, Punjab/Haryana, India

Department of Gastroenterology, Institute of Medical Sciences

Varanasi, Uttar Pradesh, India