Impact of Fecal Biotherapy (FBT) on Microbial Diversity in Patients With Moderate to Severe Inflammatory Bowel Disease
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Recipients' fecal microbial diversity after FMT, when compared to baseline
研究概览
简要总结
The human immune system is usually tolerant of the millions of beneficial commensal bacteria (the microbiome), which colonize the healthy intestinal tract. In contrast, patients with Inflammatory Bowel Disease (IBD) may play host to an imbalanced mix of such intestinal bacteria, which initiates abnormal immune responses in susceptible individuals. The resulting inflammation that occurs in the gastrointestinal tract damages the intestinal lining, leading to symptoms (such as intractable diarrhea, pain or weight loss), heightened cancer risk, other serious complications with substantial morbidity and even death. Current therapies for IBD focus on suppressing the excessive immune response to these bacteria, but have major side effects and do not address any role of the microbiome in disease development.
The investigators hypothesize that there is heightened intraluminal generation of pro-inflammatory factors by luminal "pathogenic" bacteria, such as extracellular nucleotides and purinergic derivatives, which trigger host immune cells. This results in loss of suppressive T regulatory cells with unrestrained immune cell deviation to pathogenic T helper cells that cause inflammatory responses. The investigators' proposal is that correcting the disease-provoking microbiome would beneficially improve gut microbial diversity, alter immune responses elicited in patients by such microbial products of pathogenic bacteria, and ultimately limit and suppress disease activity.
To test the hypothesis, the investigators propose to enroll patients with active Crohn's Disease, and introduce the microbiome of healthy and unrelated individuals to patient's intestinal tract, via fecal biotherapy (FBT) with all applicable safety measures. The investigators propose to comprehensively test the effects of FBT on the host microbiome, determine microbial production of inflammatory nucleotides and derivatives, which the investigators suggest might impact the host immune response and disease activity in patients with IBD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •(Patients):
- •CD confirmed by biopsy for > 3 months duration
- •Active disease (Harvey-Bradshaw Index > 5
- •Failed standard therapy with; stable doses of 5-ASA >2 weeks; thiopurines >3 months; or is steroid dependent at a dose <20mg/d; (inability to taper off steroid for longer than 1 week)
- •Stable medication regimen for >2 weeks.
- •Age > 18 years old
排除标准
- •(Patients):
- •Diagnosis of indeterminate colitis, or proctitis alone
- •Severe or fulminate colitis
- •Women who are pregnant or nursing
- •Patients who are unable to give informed consent
- •Patients who are unable or unwilling to undergo colonoscopy with moderate sedation (>ASA class II)
- •Patients who have previously undergone FMT
- •Patients who have a confirmed malignancy or cancer
- •Patients who are immunocompromised
- •Treatment within last 12 weeks with cyclosporine, tacrolimus, infliximab, adalimumab, certolizumab, natalizumab, thalidomide
- •Antibiotic use within 2-months of start date
- •Participation in a clinical trial in the preceding 30 days or simultaneously during this trial
- •Probiotic use within 30 days of start date
- •Rectal therapy within 14 days of start date
- •Decompensated cirrhosis
- •Congenital or acquired immunodeficiencies
- •Other comorbidities including:
- •Diabetes mellitus, cancer, systemic lupus, must be able to tolerate conscious sedation with colonoscopy
- •Chronic kidney disease as defined by a GFR <60mL/min/1.73m2 44
- •History of rheumatic heart disease, endocarditis, or valvular disease due to risk of bacteremia from colonoscopy
- •Steroid dose >20mg/day
研究组 & 干预措施
Fecal Microbial Transplantation
干预措施: Fecal Microbial Transplantation (Biological)
结局指标
主要结局
Recipients' fecal microbial diversity after FMT, when compared to baseline
时间窗: 12 weeks
Safety of FMT in patients with Crohn's disease, as measured by number and nature of adverse events
时间窗: 24 weeks
次要结局
- Recipients' fecal microbial diversity at 4 and 8 weeks after FMT, when compared to baseline(8 weeks)
- Mean change in Short Inflammatory Bowel Disease Questionnaire (sIBDQ) score(12 weeks)
- Percentage of patients with mucosal healing (CDEIS score <1)(12 weeks)
- Mean change in CRP levels(12 weeks)
- Percentage of patients in clinical remission (those with an HBI score at week 12 <5)(12 weeks)
- Tolerability score(2 weeks)
- Percentage of patients in endoscopic remission (CDEIS score <3)(12 weeks)
- Mean change in Harvey Bradshaw Index (HBI) score(12 weeks)
- Mean change in Crohn's Disease Endoscopic Index of Severity (CDEIS) score(12 weeks)
研究者
Alan C. Moss
Associate Professor of Medicine
Beth Israel Deaconess Medical Center