Randomized, Double-blinded, Placebo-controlled Trial of Fecal Microbiota Transplantation (FMT) for Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 3
- 主要终点
- Within and Between Group Comparisons of Disease Severity as Determined by Irritable Bowel Syndrome-Symptom Severity Score (IBS-SSS)
研究概览
简要总结
The objectives of this study are (1) to determine the efficacy of fecal microbiota transplantation (FMT), given as oral capsules, compared with placebo for the treatment of refractory diarrhea-predominant irritable bowel syndrome (IBS-D); (2) determine the impact of FMT on the intestinal microbiome of patients with IBS-D; and (3) assess the safety, feasibility, and tolerability of FMT for patients with IBS-D.
详细描述
This is a multicenter study including Montefiore Medical Center, Concorde Medical Group PLLC and the Medical Research Center of Connecticut/Yale-New Haven Hospital Langone Medical Center. Patients with IBS-D will be recruited from outpatient gastroenterology clinics at these institutions and referrals from the medical community.
FMT capsules and placebo capsules, provided by OpenBiome, Medford, MA, will be used for this study. Patients will be randomized to undergo FMT using fecal capsules (experimental group) or placebo capsules (control group) via a computer-generated program. All patients will cross-over into the alternate arm of the study at 12 weeks. Therefore, all patients enrolled will receive the experimental drug during the course of the study. Each patient will be enrolled in the study for a total of 6 months.
Intestinal microbiome analyses using DNA sequencing and non-cultivation-based approaches (16S DNA technology) will be performed in all patients in the experimental and control groups to assess stability of the microbiome over time.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 19 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •age 19-65 years
- •established diagnosis of IBS-D as determined by Rome III Criteria
- •moderate-severe disease activity (as determined by an IBS-Symptom Severity Score ≥175)
- •persistent symptoms despite conventional therapy
- •normal colonoscopy with biopsies in the past for work-up of IBS symptoms
- •negative work-up for celiac disease either by duodenal biopsies or negative serologies
排除标准
- •pregnancy
- •cognitive impairment or severe neuropsychiatric comorbidities who are incapable of providing their own informed consent
- •severely immunocompromised or immunosuppressed patients (e.g., organ transplant recipients, severe neutropenia with an absolute neutrophil count of <500cells/mL, current treatment or treatment within 3 months with anti-neoplastic agents and HIV-positive patients with CD4 counts <200cells/mm^3)
- •treated with any antibiotics in the 3 months prior to FMT
- •GI symptoms can be explained by the presence of an underlying organic disease including, underlying inflammatory bowel disease, infectious enteritis, previously established and untreated small intestinal bacterial overgrowth or known motility disorder
- •previous FMT
- •severe (anaphylactic) food allergy
- •unable to comply with protocol requirements
- •American Society of Anesthesiologists (ASA) Physical Status classification IV and V
- •acute illness or fever on the day of planned FMT will be excluded (not randomized) with the option of including that subject at a future date
- •new antidepressant started or dose of antidepressant change <3 months prior to enrollment
- •elevated ESR or CRP within the past 3 months
- •baseline laboratory abnormalities on CBC, chemistry or liver tests
- •pain score >75 on IBS-SSS
研究组 & 干预措施
FMT capsules
Intervention: Fecal microbiota transplantation capsules containing extensively screened donor stool, prepared by OpenBiome, Medford, MA. 25 FMT capsules will be take on three consecutive days.
干预措施: Fecal microbiota transplantation capsules (Drug)
Placebo capsules
Intervention: Placebo capsules that do not contain donor stool or any active drug, prepared by OpenBiome, Medford, MA. 25 placebo capsules will be taken on three consecutive days.
干预措施: Placebo capsules (Drug)
结局指标
主要结局
Within and Between Group Comparisons of Disease Severity as Determined by Irritable Bowel Syndrome-Symptom Severity Score (IBS-SSS)
时间窗: Baseline, Week 12 (before cross-over), Week 24
Within and between group comparisons of changes (from baseline) in Irritable Bowel Syndrome-Symptom Severity Score (IBS-SSS), obtained via administration of a Questionnaire, for each of the two arms/groups (FMT capsules first, and placebo capsules first). The scale range was 0-500 (min-max). Scores were averaged among time points to yield an overall mean score. Higher scores were indicative of greater disease severity (worse outcome). Subjects were categorized as having mild (75-175), moderate (175-300), or severe (\>300) irritable bowel syndrome (IBS) based on symptomology. Only the following time points were analyzed: Baseline vs Week 12 and Week 24.
次要结局
- Within and Between Group Comparisons of Quality of Life as Determined by the Irritable Bowel Syndrome-Quality of Life (IBS-QOL) Score(Baseline, Week 12 (before cross-over), Week 24)
- Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation)(Baseline and Week 1)
- Anxiety as Measured by the Hospital Anxiety and Depression Scale (HADS). HADS-A (Anxiety)(Baseline, Week 12 (before cross-over), Week 24)
- Depression as Measured by the Hospital Anxiety and Depression Scale (HADS). HADS-D (Depression)(Baseline, Week 12 (before cross-over), Week 24)
- Bowel Consistency as Measured by the Bristol Stool Form Scale (BSFS)(Baseline, Week 12 (before cross-over), Week 24)
- Number of Participants With Adverse Events as a Measure of Safety and Tolerability(All AEs over 24 weeks)
- Satisfaction With Fecal Microbiota Transplantation (FMT)(Week 12 following administration of FMT)
- Change in Bowel Habits and Abdominal Pain After Fecal Microbiota Transplantation (FMT)(Week 12 following administration of FMT)
- Number of Doctor or Emergency Department (ED) Visits Post-Fecal Microbiota Transplantation (Post-FMT) for Irritable Bowel Syndrome-D (IBS-D) Related Symptoms(Week 12 following administration of FMT)
- Initiation of New Medications Post-FMT for the Treatment of IBS-D Symptoms(Week 12 following administration of FMT)
- Patient Attitudes Towards Fecal Microbiota Transplantation (FMT)(Week 12 following administration of FMT)
- Tolerability of Fecal Microbiota Transplantation (FMT)(Week 12 following administration of FMT)
研究者
Olga Aroniadis
M.D.
Montefiore Medical Center