Efficacy of Microbiome Manipulation Strategies (fecAL Microbial Transplantation OR Anti-inflammatory diEt OR Both) in Combination With 5-aminosalicylic Acid for Induction and Maintenance of Remission in Patients With Mild to Moderate tReatment Naive Active Ulcerative Colitis: a Multicentre Double-blind Factorial Randomized Controlled Trial(ALTER-UC)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 220
- 试验地点
- 7
- 主要终点
- Proportion of patients having clinical remission and endoscopic response at week 10
研究概览
简要总结
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.
详细描述
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)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with treatment-naive ulcerative colitis of any disease extent. Patients with proctitis will be limited to 25% of the entire pool of patients.
- •Mild to moderate endoscopically active disease (modified Mayo clinic score (mMS) 3-6, with Mayo endoscopic score greater than or equal to 2).
- •Aged between 18-75 years.
- •Patients giving consent for FMT.
- •Patients who agree to adhere to the diet schedule.
- •Patients on oral or topical ASA for less than 4 weeks.
- •Patients on oral steroids/ topical steroids for less than 1 week.
- •Infective colitis should be ruled out by histologic appearance of crypt architecture distortion/basal plasmacytosis, or two sigmoidoscopies, at least 7 days apart showing evidence of endoscopic activity.
排除标准
- •Patients with severe disease (mMS equal to 7-9)
- •Clinical signs of fulminant colitis or toxic megacolon
- •Presence of IBD-unclassified, microscopic colitis, ischemic colitis, infectious colitis, or clinical findings suggestive of Crohns Disease.
- •Patients who have been initiated on other therapies (biologicals or immunosuppressants (azathioprine/ 6-mercaptoprine/methotrexate)) for greater than 2 weeks
- •Patients requiring hospitalization
- •Pregnant or lactating women
- •Patients with current or recent history of clinically severe, progressive, or uncontrolled renal, hepatic, haematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiac or neurological disease.
- •Positive assay or stool culture for pathogens (ova and parasite examination, bacteria) or positive test for Clostridioides difficile toxin at screening#
- •Patients infected with human immunodeficiency virus (HIV) # 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.
结局指标
主要结局
Proportion of patients having clinical remission and endoscopic response at week 10
时间窗: 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.
Proportion of patients having clinical remission and endoscopic response at week 48
时间窗: 48 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.
次要结局
- Proportion of Patients achieving Symptomatic Remission at Week 48(48 weeks)
- Proportion of Patients achieving Endoscopic Response at Week 48(48 weeks)
- Proportion of Patients achieving Endoscopic Remission at Week 48(48 weeks)
- Proportion of Patients achieving Histologic Remission at Week 48(48 weeks)
- Proportion of Patients Achieving Biomarker Remission at Week 48(48 weeks)
- Fecal Microbiome and Metabolite Signature at Week 48(48 weeks)
- Dynamics of microbiome engraftment at week 48(48 weeks)
- Proportion of Patients Experiencing Adverse Events at Week 48(48 weeks)
- Proportion of patients having adverse events at week 6(6 weeks)
- Proportion of patients having adverse events at week 26(26 weeks)
- 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)
- Proportion of Patients Achieving Endoscopic Remission at Week 10(10 weeks)
- Proportion of Patients Achieving Histologic Remission at Week 10(10 weeks)
- Proportion of Patients Achieving Biomarker Remission at Week 10(10 weeks)
- Proportion of Patients Experiencing Adverse Events at Week 10(10 weeks)
- Fecal Microbiome and Metabolite Signature at Week 10(10 weeks)
- Dynamics of microbiome engraftment at week 10(10 weeks)
- Proportion of patients having clinical response at week 48(48 weeks)
- Proportion of patients having clinical remission at week 48(48 weeks)
- Proportion of Patients Achieving Symptomatic Response at Week 48(48 weeks)
研究者
Prof. Vineet Ahuja
Professor
All India Institute of Medical Sciences, New Delhi