Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| EMDR/CARE/12/2023-0000572 | Other Grant/Funding Number | Indian Council of Medical Research |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Post Graduate Institute of Medical Education and Research, Chandigarh | OTHER |
| Institute of Medical Sciences of the Banaras Hindu University, India | OTHER |
| Dayanand Medical College and Hospital | OTHER |
Not provided
Not provided
Not provided
Ulcerative colitis (UC) is a chronic inflammatory condition affecting the colon and rectum, characterized by mucosal inflammation and symptomslike diarrhea, abdominal pain, and rectal bleeding. It is a subtype of inflammatory bowel disease (IBD) and results from a combination of genetic predisposition, environmental factors, and immune dysregulation. UC is associated with significant gut microbiota dysbiosis, marked by reduced beneficial bacteria and increased harmful taxa. With rising prevalence in developing countries like India, effective and accessible treatments remain a critical need. This multi-center randomized factorial double blind placebo controlled treat through trial will utilize a 2x 2 factorial design to randomize patients of mild to moderate (modified Mayo score 3-6) endoscopically active (Mayo endoscopic score: >1) treatment naÃive UC in 1:1:1:1 ratio to fecal microbiota transplantation (FMT) + anti-inflammatory diet (AID) +5-aminisalicylic acid (5-ASA) (Intervention, Group A) vs fecal microbiota transplantation + sham diet +5-aminisalicylic acid(Intervention, Group B) vs sham transplantation + anti-inflammatory diet +5-aminisalicylic acid(Intervention, Group C) vs sham transplantation
+ sham diet +5-aminisalicylic acid(Control, Group D). In the induction phase patients will receive FMT/sham transplantation at 0, 2 and 6 weeks along with AID/Sham diet and 5-ASA for 10 weeks. Outcome will be assessed at 10 weeks, Treatment failure will be out of trial. Patients with clinical response at 10 weeks will continue in the maintenance phase and will receive FMT/sham transplantation at 10, 18, 26, 34, and 42 weeks along with AID/Sham diet and 5-ASA till48 weeks. Outcome will be assessed at 48 weeks. Treatment failure will be out of trial. The primary efficacy outcome will evaluate fecal microbial transplantation or anti- inflammatory diet or combination of both vs placebo. The primary outcomes are proportion of patients having clinical remission and endoscopic response at week 10 and proportion of patients having clinical remission and endoscopic remission at week 48. Modified intention to treat analysis will be done and patients who receive at least 1 dose of intervention will be included for outcome assessment.
This study is a multi-center, double-blind, 2 × 2 factorial, randomized sham-controlled trial designed to evaluate the effects of fecal microbiota transplantation (FMT) and dietary modification in treatment-naïve patients with mild to moderate active ulcerative colitis (UC). The trial consists of four treatment arms:
FMT + Anti-inflammatory Diet (AID) + 5-ASA (Group A) FMT + Sham Diet + 5-ASA (Group B) Sham Transplantation + AID + 5-ASA (Group C) Sham Transplantation + Sham Diet + 5-ASA (Group D) All groups receive 5-aminosalicylic acid (5-ASA) as the standard medical therapy.
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 Lokmanya Tilak Municipal Medical College, Mumbai, India IIIT-Delhi, India (for microbiome analysis)
Intervention Details Fecal Microbiota Transplantation (FMT) Patients receive three FMT sessions (weeks 0, 2, 6) during induction and additional 8-weekly maintenance sessions (weeks 10, 18, 26, 34, 42) for responders.
FMT is delivered via colonoscopy; at week 0, it is instilled into the right colon/terminal ileum (post bowel preparation), while for maintenance sessions, it is instilled in the left colon without bowel preparation.
Each FMT dose is 50 g stool, freshly prepared within 4 hours of collection. Multiple donors are used to ensure microbiome diversity
Anti-Inflammatory Diet (AID) Patients assigned to AID receive a nutritionally tailored diet that promotes T-regulatory cell expansion, microbiome stability, and gut barrier integrity.
The diet excludes gluten-based grains, dairy products, and pro-inflammatory foods while including fermented foods, cruciferous vegetables, and polyphenols.
Patients are provided diet charts, receive dietary counseling, and are monitored via diet app named IBDNutricare.
Sham Interventions Sham FMT: Instead of donor stool, patients receive sterile water infusions via colonoscopy at the same time points as FMT.
Sham Diet: Patients receive dietary counselling without specific modifications
Randomization and Blinding Central randomization is conducted via REDCap. Block randomization will be done in which blocks of 8 will be created for the randomization. Further, stratified randomization will also be done in which <25% Proctitis involving Ulcerative Colitis patients.
Blinding:
Patients, investigators collecting clinical data, and those assessing endoscopic images are blinded. The endoscopist administering FMT and the dietitian providing dietary counseling are unblinded
Data Collection and Assessments Baseline Assessments (Week 0) Clinical Evaluation: Patient-reported outcomes (PRO-2), stool frequency, rectal bleeding assessments.
Laboratory Tests: Hemogram, renal/liver function, CRP, ESR, fecal calprotectin, and microbiome profiling.
Endoscopy: Mayo Endoscopic Score (MES) assessment with high-definition recordings.
Histology: Biopsy samples assessed using Robarts Histologic Index (RHI) and Distribution Chronicity and Activity (DCA) score
Follow-up Assessments Week 10 (Induction phase endpoint): Endoscopy, histology, laboratory tests. Week 48 (Maintenance phase endpoint): Same assessments as baseline. Microbiome Analysis: Fecal samples collected at baseline, 10 weeks, and 48 weeks for metagenomics and metabolomics
Safety Monitoring Adverse events graded using CTCAE criteria (Grade 1-5). Serious adverse events (SAEs) include hospitalization, disability, or life-threatening conditions
Data Management Data is collected using paper Case Report Forms (CRF's) and then data will be entered in REDCap.
Endoscopic images and videos are securely stored and centrally reviewed.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sham transplantation with sham diet | Sham Comparator |
|
|
| Fecal Microbiota Transplant(FMT) and Sham diet | Experimental |
|
|
| Anti-inflammatory diet and sham transplantation | Experimental |
|
|
| Fecal Microbiota Transplant(FMT) and Anti inflammatory diet | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sham transplantation | Other | Sham FMT will involve saline infusion via colonoscopy |
|
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of patients having clinical remission and endoscopic response at week 10 | Proportion of patients having-
| 10 weeks |
| Proportion of patients having clinical remission and endoscopic response at week 48 | Proportion of patients having-
| 48 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of patients having clinical response at week 10 | Proportion of patients having clinical response (Defined as a decrease from baseline in the mMS of greater than or equal to 2 points and at least a 30 percent reduction from baseline) 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.) |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Prof Vineet Ahuja, DM Gastroenterology | Contact | +91-9810707170 | vineet.aiims@gmail.com | |
| Dr Himanshu Narang, DM Gastroenterology | Contact | +91-8800316504 | h92narang@gmail.com |
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Gastroenterology, Lisie Hospital | Not yet recruiting | Kochi | Kerala | India |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Indraprastha Institute of Information Technology Delhi | OTHER |
| Lisie Hospital | OTHER |
| Indian Council of Medical Research | OTHER_GOV |
| Lokmanya Tilak Municipal Medical College and Hospital | OTHER |
Not provided
Not provided
Not provided
Not provided
|
| Anti inflammatory diet | Other | The modified diet plan will be given to each study participant |
|
| Fecal Microbial Transplantation | Other | This will involve colonoscopic instillation of fecal transplant |
|
| Sham diet | Other | Dietary counselling alone |
|
| 10 weeks |
| Proportion of patients having clinical remission at week 10 | Proportion of patients having clinical remission which is defined as an mMS of 0 to 2, including the following three components: 1) Stool frequency sub score = 0 (or = 1 with a ≥ 1-point decrease from baseline), 2) Rectal bleeding sub score = 0 3) Centrally read endoscopy sub score = 0 or 1 (score of 1 modified to exclude friability) 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.) | 10 weeks |
| Proportion of Patients achieving Symptomatic Response at Week 10 | Proportion of Patients Achieving Symptomatic Response which is defined as Decrease from baseline ≥ 30% in composite Rectal Bleeding sub score and Stool Frequency sub score and a ≥ 1-point decrease from baseline in RB sub score or an absolute RB sub score ≤ 1) Stool Frequency Subscore: Range: 0 to 3 (typically; the exact range may vary depending on the scale used) Lower Scores = Better Outcome (A score of 0 indicates no stool frequency issues, while higher scores represent increasing frequency of stools, indicating worse disease activity.) Rectal Bleeding Subscore: Range: 0 to 3 (typically; range may vary depending on the version used) Lower Scores = Better Outcome (A score of 0 indicates no rectal bleeding, while higher scores represent increasing severity of rectal bleeding, indicating worse disease activity.) | 10 weeks |
| Proportion of Patients achieving Symptomatic Remission at week 10 | Proportion of Patients achieving Symptomatic Remission which is defined as Stool Frequency subscore = 0 (or = 1 with a ≥ 1-point decrease from baseline) and Rectal Bleeding subscore = 0 Stool Frequency Subscore: Range: 0 to 3 (typically; the exact range may vary depending on the scale used) Lower Scores = Better Outcome (A score of 0 indicates no stool frequency issues, while higher scores represent increasing frequency of stools, indicating worse disease activity.) Rectal Bleeding Subscore: Range: 0 to 3 (typically; range may vary depending on the version used) Lower Scores = Better Outcome (A score of 0 indicates no rectal bleeding, while higher scores represent increasing severity of rectal bleeding, indicating worse disease activity.) | 10 weeks |
| Proportion of Patients Achieving Endoscopic Response at Week 10 | Proportion of Patients Achieving Endoscopic Response which is defined as decrease in Modified Endoscopic Score ≥1 points 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 Achieving Endoscopic Remission at Week 10 | Proportion of Patients achieving Endoscopic Remission which is defined as Modified Endoscopy Score=0 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 Achieving Histologic Remission at Week 10 | Proportion of Patients Achieving Histologic Remission (Robarts histopathology index score <3 with lamina propria neutrophils score = 0 and neutrophil in epithelium score=0; DCA (Distribution/ chronicity/ activity) score, A=0) Robarts Histopathology Index (RHI): Full Title: Robarts Histopathology Index Range: 0 to 16 (varies depending on the specific version used, but typically it is in this range) Lower Scores = Better Outcome (A lower score indicates less histologic damage or inflammation.) Lamina Propria Neutrophils Score: Range: 0 to 3 Lower Scores = Better Outcome (A score of 0 indicates no neutrophils present, which is a sign of histologic remission.) Neutrophils in Epithelium Score: Range: 0 to 3 Lower Scores = Better Outcome (A score of 0 indicates no neutrophils in the epithelium, which is also a sign of histologic remission.) DCA Score: Full Title: Distribution/Chronicity/Activity Score Range: 0 to 3 Lower Scores = Better Outcome (score of 0 =no activity | 10 weeks |
| Proportion of Patients Achieving Biomarker Remission at Week 10 | Proportion of Patients Achieving Biomarker Remission (Defined as fecal calprotectin ≤150 mcg/g) | 10 weeks |
| Proportion of Patients Experiencing Adverse Events at Week 10 | Proportion of Patients experiencing Adverse events which will be assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) and graded as follows: Grade 1: Mild symptoms (no intervention required). Grade 2: Moderate symptoms (non-operative intervention required). Grade 3: Severe symptoms (operative intervention required). Grade 4: Life-threatening consequences (urgent intervention required). Grade 5: Death. | 10 weeks |
| Fecal Microbiome and Metabolite Signature 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 |
| Dynamics of microbiome engraftment at week 10 | It involves capturing donor-to-recipient microbiome transfer/shift at species and strain-level will be performed as an investigation of 'FMT events', where in each event will include triad of samples: the donor, the Pre-FMT and the Post-FMT sample from the recipient patient. Species-level donor-to-recipient shifts will be investigated by computing the Bray-Curtis and Kendall distances between all three sample-pairs of the triad. Kendall distances capture the variations and similarities amongst samples in terms of the relative hierarchical ranking of different taxa within a community, Bray-Curtis distances capture the differences in the abundances of different taxa across two communities. Both these distance measure-based approaches will be utilized the fraction of recipient microbiome that is modulated by the donor microbiome in terms of both composition and species-level hierarchy. | 10 weeks |
| Proportion of patients having clinical response at week 48 | Proportion of patients having clinical response (Defined as a decrease from baseline in the mMS of greater than or equal to 2 points and at least a 30 percent reduction from baseline) 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.) | 48 weeks |
| Proportion of patients having clinical remission at week 48 | Proportion of patients having clinical remission which is defined as an modified mayo score of 0 to 2, including the following three components: 1) Stool frequency sub score = 0 (or = 1 with a ≥ 1-point decrease from baseline), 2) Rectal bleeding sub score = 0 3) Centrally read endoscopy sub score = 0 or 1 (score of 1 modified to exclude friability) 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.) | 48 weeks |
| Proportion of Patients Achieving Symptomatic Response at Week 48 | Proportion of Patients Achieving Symptomatic Response which is defined as Decrease from baseline ≥ 30% in composite Rectal Bleeding sub score and Stool Frequency sub score and a ≥ 1-point decrease from baseline in RB sub score or an absolute RB sub score ≤ 1) Stool Frequency Subscore: Range: 0 to 3 (typically; the exact range may vary depending on the scale used) Lower Scores = Better Outcome (A score of 0 indicates no stool frequency issues, while higher scores represent increasing frequency of stools, indicating worse disease activity.) Rectal Bleeding Subscore: Range: 0 to 3 (typically; range may vary depending on the version used) Lower Scores = Better Outcome (A score of 0 indicates no rectal bleeding, while higher scores represent increasing severity of rectal bleeding, indicating worse disease activity.) | 48 weeks |
| Proportion of Patients achieving Symptomatic Remission at Week 48 | Proportion of Patients achieving Symptomatic Remission which is defined as Stool Frequency subscore = 0 (or = 1 with a ≥ 1-point decrease from baseline) and Rectal Bleeding subscore = 0 Stool Frequency Subscore: Range: 0 to 3 (typically; the exact range may vary depending on the scale used) Lower Scores = Better Outcome (A score of 0 indicates no stool frequency issues, while higher scores represent increasing frequency of stools, indicating worse disease activity.) Rectal Bleeding Subscore: Range: 0 to 3 (typically; range may vary depending on the version used) Lower Scores = Better Outcome (A score of 0 indicates no rectal bleeding, while higher scores represent increasing severity of rectal bleeding, indicating worse disease activity.) | 48 weeks |
| Proportion of Patients achieving Endoscopic Response at Week 48 | Proportion of Patients Achieving Endoscopic Response which is defined as decrease in Modified Endoscopic Score ≥1 points 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 |
| Proportion of Patients achieving Endoscopic Remission at Week 48 | Proportion of Patients achieving Endoscopic Remission which is defined as Modified Endoscopy Score=0 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 |
| Proportion of Patients achieving Histologic Remission at Week 48 | Proportion of Patients Achieving Histologic Remission (Robarts histopathology index score <3 with lamina propria neutrophils score = 0 and neutrophil in epithelium score=0; DCA (Distribution/ chronicity/ activity) score, A=0) | 48 weeks |
| Proportion of Patients Achieving Biomarker Remission at Week 48 | Proportion of Patients Achieving Biomarker Remission (Defined as fecal calprotectin ≤150 mcg/g) | 48 weeks |
| Fecal Microbiome and Metabolite Signature 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 |
| Dynamics of microbiome engraftment at week 48 | It involves capturing donor-to-recipient microbiome transfer/shift at species and strain-level will be performed as an investigation of 'FMT events', where in each event will include triad of samples: the donor, the Pre-FMT and the Post-FMT sample from the recipient patient. Species-level donor-to-recipient shifts will be investigated by computing the Bray-Curtis and Kendall distances between all three sample-pairs of the triad. Kendall distances capture the variations and similarities amongst samples in terms of the relative hierarchical ranking of different taxa within a community, Bray-Curtis distances capture the differences in the abundances of different taxa across two communities. Both these distance measure-based approaches will be utilized the fraction of recipient microbiome that is modulated by the donor microbiome in terms of both composition and species-level hierarchy. | 48 weeks |
| Proportion of Patients Experiencing Adverse Events at Week 48 | Proportion of Patients experiencing Adverse events which will be assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) and graded as follows: Grade 1: Mild symptoms (no intervention required). Grade 2: Moderate symptoms (non-operative intervention required). Grade 3: Severe symptoms (operative intervention required). Grade 4: Life-threatening consequences (urgent intervention required). Grade 5: Death | 48 weeks |
| Proportion of patients having adverse events at week 6 | Proportion of Patients experiencing Adverse events which will be assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) and graded as follows: Grade 1: Mild symptoms (no intervention required). Grade 2: Moderate symptoms (non-operative intervention required). Grade 3: Severe symptoms (operative intervention required). Grade 4: Life-threatening consequences (urgent intervention required). Grade 5: Death. | 6 weeks |
| Proportion of patients having adverse events at week 26 | Proportion of Patients experiencing Adverse events which will be assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) and graded as follows: Grade 1: Mild symptoms (no intervention required). Grade 2: Moderate symptoms (non-operative intervention required). Grade 3: Severe symptoms (operative intervention required). Grade 4: Life-threatening consequences (urgent intervention required). Grade 5: Death | 26 weeks |
| Lokmanya Tilak Municipal General Hospital and Lokmanya Tilak Municipal Medical College, Sion | Not yet recruiting | Mumbai | Maharashtra | India |
|
| Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences | Recruiting | New Delhi | National Capital Territory of Delhi | 110029 | India |
|
| Department of Gastroenterology, Dayanand Medical College | Not yet recruiting | Ludhiana | Punjab | India |
|
| Department of Gastroentrology, Postgraduate Institute of Medical Education and Research | Not yet recruiting | Chandigarh | Punjab/Haryana | India |
|
| Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University | Not yet recruiting | Varanasi | Uttar Pradesh | India |
|
| ID | Term |
|---|---|
| D003093 | Colitis, Ulcerative |
| ID | Term |
|---|---|
| D003092 | Colitis |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D015212 | Inflammatory Bowel Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
Not provided
Not provided