AIM-IBD: A Phase 2b Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial of a Microbiome-Targeted Food Supplement Versus Placebo in Adults With Mild-to-Moderate, Objectively Active Ulcerative Colitis
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 162
- 试验地点
- 1
研究概览
简要总结
This Phase 2b randomized, double-blind, placebo-controlled, multicenter trial will evaluate the efficacy and safety of a once-daily oral microbiome-targeted food supplement compared with matching placebo in adults with mild-to-moderate, objectively active ulcerative colitis. The supplement is food-grade and is intended for use either alongside stable standard ulcerative colitis therapy (5-aminosalicylic acid/mesalamine) or in participants not currently on any inflammatory bowel disease therapy.
Approximately 162 participants will be enrolled at university hospital centers in Turkey and randomized in a 1:1 ratio to receive either the food supplement or matching placebo for 24 weeks, in addition to their existing background therapy as defined by eligibility.
The primary objective is to determine whether the supplement increases the proportion of participants achieving composite clinical-plus-biochemical remission at Week 24. This composite endpoint requires absence of rectal bleeding, improvement in stool frequency, fecal calprotectin ≤250 micrograms/g, and no rescue therapy, prohibited treatment escalation, ulcerative colitis-related hospitalization, colectomy, or discontinuation for lack of efficacy before Week 24.
Key secondary endpoints include endoscopic improvement, deep biochemical remission, change in fecal calprotectin, change in partial Mayo score, corticosteroid-free composite remission, change in quality of life, change in C-reactive protein, time to treatment failure, and safety. Exploratory analyses will assess stool microbiome composition, eukaryotic carriage including Blastocystis, and associations between baseline microbiome features and treatment response.
详细描述
Ulcerative colitis is a chronic inflammatory disease of the colonic mucosa characterized by relapsing and remitting symptoms including rectal bleeding, increased stool frequency, urgency, and impaired quality of life. Although 5-aminosalicylic acid (5-ASA, mesalamine) is the foundation of treatment for mild-to-moderate disease, a meaningful proportion of patients have persistent symptoms or ongoing objective inflammation despite optimized therapy, and many wish to defer immunosuppressive or biologic therapy. The intestinal microbiota of patients with active ulcerative colitis differ from those of healthy individuals, with depletion of short-chain fatty acid-producing taxa, reduced diversity, and altered microbial metabolism. Food-grade microbiome-targeted interventions therefore offer a non-immunosuppressive option to modify intestinal microbial ecology and inflammatory activity in this gap.
AIM-IBD is designed as a Phase 2b, randomized, double-blind, placebo-controlled, parallel-group, multicenter proof-of-concept trial. Randomization is centralized and stratified by study site and baseline 5-ASA status. Participants, investigators, site staff, outcome assessors, endoscopy readers, central laboratory personnel, microbiome and metabolomics analysts, and the primary trial statistician remain blinded to allocation until database lock, except where emergency unblinding is required for participant safety. Blinding integrity is formally assessed at Weeks 12 and 24 using participant and investigator treatment-guess questionnaires summarized with Bang's and James's blinding indices.
The Week 24 endoscopic assessment is by protocol-mandated flexible sigmoidoscopy with dual independent blinded reading and adjudication of discordant scores. Fecal calprotectin and other biomarkers are measured in a central laboratory. Stool samples for microbiome and metabolomics analyses are collected at baseline, Week 12, and Week 24 under a harmonized study procedure.
The planned sample size of 162 participants (81 per arm) provides approximately 90% power to detect a 23-percentage-point absolute difference in the Week 24 primary endpoint (placebo 12% vs active 35%), with two-sided alpha 0.05 and approximately 15% attrition. This ambitious effect size is defensible only because the trial is designed as a high-signal proof-of-concept study: the enrolled population is enriched for objectively active disease (fecal calprotectin ≥250 µg/g and rectal bleeding subscore ≥1 at screening), background therapy is held constant (stable 5-ASA at unchanged dose for ≥8 weeks, or no inflammatory bowel disease therapy), and patients with recent advanced-therapy exposure or current corticosteroids are excluded. Sensitivity analyses across a range of placebo and active response assumptions are prespecified in the Statistical Analysis Plan.
The intention-to-treat population is the primary analysis population. The primary composite endpoint is analyzed using stratified Cochran-Mantel-Haenszel methodology adjusted for randomization stratification factors. Key secondary endpoints are tested in a fixed-sequence hierarchical procedure controlling the family-wise error rate at two-sided alpha 0.05. The estimand framework follows ICH E9(R1): treatment failures (rescue therapy, prohibited escalation, ulcerative colitis-related hospitalization, colectomy, discontinuation for lack of efficacy) are handled under a composite strategy, with a supplementary treatment-policy estimand and prespecified sensitivity analyses (multiple imputation, tipping-point analysis, pattern-mixture).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Participants, care providers, investigators, site study staff, outcome assessors, endoscopy readers, central laboratory personnel, microbiome and metabolomics analysts, and the primary trial statistician will remain blinded to treatment allocation until database lock. The investigational product and placebo will be matched in appearance, packaging, administration schedule, and organoleptic characteristics as closely as technically feasible.
The randomization schedule will be generated and held by an independent statistician or designated unblinded party who is not involved in participant recruitment, clinical care, outcome assessment, or primary analysis. Emergency unblinding will be permitted only when knowledge of treatment allocation is essential for immediate clinical management and will be documented according to the study's standard operating procedure.
Blinding integrity will be assessed at Weeks 12 and 24 using participant and investigator treatment-guess questionnaires.
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
- •Adults aged 18 to 75 years inclusive at screening.
- •Documented diagnosis of ulcerative colitis established at least 3 months before screening, based on standard clinical, endoscopic, and histologic criteria.
- •Mild-to-moderate active ulcerative colitis defined by a partial Mayo score of 4 to 8 at screening.
- •Rectal bleeding subscore of at least 1 at screening.
- •Objective intestinal inflammation defined by fecal calprotectin of at least 250 micrograms per gram at screening, measured by the central laboratory or by a validated harmonized assay.
- •Eligible disease extent: left-sided colitis or extensive/pancolitis. Proctosigmoiditis is eligible if inflammation extends beyond isolated proctitis and is measurable by study endoscopy. Isolated ulcerative proctitis (E1 only) is eligible only within a prespecified cap not exceeding 10 percent of total enrollment.
- •Either no current ulcerative colitis-directed therapy, or stable oral and/or rectal 5-aminosalicylate (5-ASA, mesalamine) therapy at unchanged dose for at least 8 weeks before randomization, with intent to continue at the same unchanged dose through Week 24 unless rescue therapy is clinically required.
- •Able and willing to provide written informed consent.
- •Able and willing to comply with study visits, stool sampling, endoscopy, medication restrictions, and diary/patient-reported outcome completion.
- •Participants of childbearing potential must agree to use a highly effective method of contraception during dosing and for at least 4 weeks after the last dose, in accordance with EMA/CTFG guidance and local ethics requirements.
排除标准
- •Crohn disease, inflammatory bowel disease-unclassified, microscopic colitis, ischemic colitis, infectious colitis, radiation colitis, or any other non-ulcerative-colitis form of colitis.
- •Severe ulcerative colitis, acute severe ulcerative colitis, fulminant colitis, toxic megacolon, or any disease severity requiring immediate hospitalization or treatment escalation in the investigator's judgment.
- •Isolated ulcerative proctitis (E1 only) outside the prespecified 10 percent enrollment cap.
- •Use of biologics, Janus kinase (JAK) inhibitors, sphingosine-1-phosphate (S1P) receptor modulators, or systemic immunosuppressants within 8 weeks before randomization, or planned use of any of these during the trial.
- •Systemic corticosteroids within 4 weeks before randomization.
- •Current budesonide-class therapy at baseline.
- •Rectal or topical corticosteroids unless discontinued at least 2 weeks before randomization.
- •Antibiotic use within 4 weeks before randomization, except topical antibiotics not expected to affect the gut microbiota.
- •Probiotic, prebiotic, synbiotic, postbiotic, fermented microbiome-directed supplement, or other non-study microbiome-directed product within 4 weeks before randomization, or planned use during the trial.
- •Active or recent Clostridioides difficile infection within 12 weeks before screening (screening uses a two-step algorithm: glutamate dehydrogenase plus toxin A/B enzyme immunoassay, with reflex nucleic acid amplification testing for discordant results).
- •Positive stool test for any clinically relevant enteric infection at screening, per local diagnostic standard operating procedures.
- •Prior colectomy, planned colectomy, known dysplasia requiring intervention, or colorectal cancer.
- •Pregnancy, breastfeeding, or planned pregnancy during the trial.
- •Uncontrolled clinically significant comorbidity, including but not limited to uncontrolled diabetes, advanced liver or renal disease, unstable cardiovascular disease, immunodeficiency, active malignancy other than adequately treated non-melanoma skin cancer, or any other condition compromising participant safety or interpretation of study results.
- •Known allergy, intolerance, or contraindication to any component of the investigational product or matching placebo.
- •Participation in another interventional clinical trial within 30 days before screening.
- •Any other condition that, in the investigator's judgment, would make participation unsafe or compromise protocol adherence.
研究组 & 干预措施
Placebo
Participants assigned to this arm will receive matching placebo orally once daily for 24 weeks, in addition to either no background ulcerative colitis therapy or stable 5-aminosalicylic acid/mesalamine therapy at an unchanged dose, according to eligibility criteria. Rescue therapy or treatment escalation is permitted at any time if clinically needed.
干预措施: Placebo (Dietary Supplement)
Microbiome-Targeting Investigational Product
Participants assigned to this arm will receive the microbiome-targeting investigational product orally once daily for 24 weeks, in addition to either no background ulcerative colitis therapy or stable 5-aminosalicylic acid/mesalamine therapy at an unchanged dose, according to eligibility criteria. Rescue therapy or treatment escalation is permitted at any time if clinically needed.
干预措施: Microbiome-Targeting Nutraceutical (Dietary Supplement)
研究者
Varol TUNALI
Chief Medical Officer (CMO)
ENBIOSIS BIOTECHNOLOGIES