Pilot Feasibility Study of Fecal Microbiota Transplant for the Treatment of Small Intestinal Bacterial Overgrowth
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Rate of Clinical Remission (post fecal microbiota transplant)
研究概览
简要总结
The objective of the study is to assess feasibility, and clinical efficacy of a novel Fecal Microbiota Transplantation protocol for the treatment of pediatric small intestinal bacterial overgrowth (SIBO).
详细描述
BACKGROUND AND RATIONALE Fecal microbiota transplant (FMT) is an established treatment for the management of recurrent Clostridioides difficile (CDI) infection in children and adults, including children with underlying immunodeficiency syndromes and extensive surgical resection. While CDI is the most common indication for FMT, this intervention has also been studied for Crohn's disease, ulcerative colitis, autism, and small intestinal bacterial overgrowth (SIBO). SIBO is a disorder in which the small bowel is colonized by excessive aerobic and anaerobic microbes normally present in the colon. This condition may cause malabsorption, bloating, bloodstream infections (BSI), and D-lactic acidosis (DLA). Treatment traditionally involves broad-spectrum antibiotic use yet this approach may promote persistent dysbiosis, multidrug resistant organisms (MDROs), and often lacks clinical efficacy. Patients with short bowel syndrome (SBS), which involves intestinal resection, dysmotility, and altered enteral feeding are at highest risk for SIBO. Pediatric SBS SIBO patients face significant impacts on quality of life, and higher rates of bacteremia and liver disease.
Specific Aims i. To determine the feasibility, and safety of administering an FMT based treatment to pediatric SBS patients with SIBO. This aim will include measures of adverse events, acceptability to children and parents, ease of administration and sample collection.
ii. To determine short-term clinical efficacy of FMT for the treatment of SIBO. This aim will include measures of time to symptom resolution, completeness of symptom resolution, change in enteral feeding tolerance, and development of any new clinical gastrointestinal symptoms after FMT. Weeks 1-4 after FMT.
iii. To determine long-term clinical efficacy of FMT for the treatment of SIBO. This aim will include measures of durability of remission, including time to recurrence of symptom resolution, severity of clinical symptoms if recurrence, sustained changes in feeding tolerance, and efficacy of repeat FMT administration (second treatment). Week 8 after FMT.
iv. To assess changes in intestinal microbial composition and function before and after FMT. This aim will attempt to identify functional changes in the intestinal microbiome that correlate with symptom resolution. These data will support future translational and clinical studies with our collaborators and support the development of new therapeutic innovations.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 3 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients 3-18 years old
- •Patients will discontinue antibiotics for at least 1 week prior to FMT
- •A diagnosis of SIBO established through lactose breath test (LBT), and showing of symptoms of SIBO
排除标准
- •Participants will not be permitted to start any new treatments (including antibiotics, probiotics, antacid treatments, or antimotility treatments) until Week 8, unless clinically indicated
- •We will exclude participants <3yo to avoid potential concerns of microbial transmission in young children, and to ensure participants are developmentally able to perform LBT
- •All potential participants should request a referral through their primary, or subspecialty physician. We would be pleased to help facilitate this contact if needed, provided the appropriate contact information can be sent.
研究组 & 干预措施
Fecal Microbiota Transpant
Participants will receive a Fecal Microbiota transplant Infusion via participants' existing enteral feeding tubes or via elective upper endoscopy (with infusion into the duodenum). Most patients with SBS at MCH and HSC have an existing enteral feeding tube (gastrostomy or jejunostomy tube).
干预措施: Fecal Microbiota Transplant (Biological)
结局指标
主要结局
Rate of Clinical Remission (post fecal microbiota transplant)
时间窗: Baseline (pre-fecal microbiota transplant), one-, four-, and eight-weeks post-fecal microbiota transplant administration.
Absence of SIBO symptoms
Change in Breath Test Results (pre/post fecal microbiota transplant)
时间窗: Baseline (pre-fecal microbiota transplant), one-, four-, and eight-weeks post-fecal microbiota transplant administration.
Lactulose breath test
Bloodwork
时间窗: Baseline and Week 8 (post-FMT)
Bloodwork will include complete blood count (CBC), C-reactive protein (CRP), ferritin, folic acid, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), serum cytokine profiles (including IL-2, IL-6, IL10, IL-18, TNF) and serum bile acids. Routine institutional testing protocols will be followed at MCH and HSC. Bloodwork outcomes are exploratory. Data will support the development of primary and secondary objectives for future studies.
Urine Metabolomics Analysis
时间窗: Baseline (pre-fecal microbiota transplant), one-, four-, and eight-weeks post-fecal microbiota transplant administration.
Collected urine will be assessed by multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS), using previously described protocols. This technique will offer additional data on microbiome functional changes. Samples will be measured centrally through the Britz-McKibbin laboratory (PBM). Urine metabolomics outcomes are exploratory.
Change in Microbiome Composition, Function (pre/post fecal microbiota transplant)
时间窗: Baseline (pre-fecal microbiota transplant), one-, four-, and eight-weeks post-fecal microbiota transplant administration.
Stool will be collected for microbiome 16S rRNA and shotgun metagenomic sequencing. Samples will be obtained from either stool (per rectum), or distal ostomy outputs (ostomy in continuity with proximal bowel). All samples will be sequenced centrally through the McMaster Genomics Centre (MGC). Samples will be stored in -80 freezers. Participants unable to bring stool samples to MCH or HSC will receive funding support for temperature-controlled courier services from home. Costs of microbiome analyses will be partially subsidized by collaborators (MS).
Change in Clinical Symptoms (pre/post fecal microbiota transplant)
时间窗: Baseline (pre-fecal microbiota transplant), one-, four-, and eight-weeks post-fecal microbiota transplant administration.
SIBO Clinical Symptom Scores will be measured using the PedsQL Gastrointestinal Symptoms Scale. This validated instrument has strong age-specific test-retest properties and has been used for functional GI disorders, which have symptoms that strongly overlap with SIBO. Participants will also report symptoms using a Likert scale (Izumo scale). Results of both will be compared.
次要结局
- Adverse Events(30 Weeks)
- Monthly Rate of Recruitment(30 weeks)
- Blood, stool specimens, breath tests, clinical symptom scores(30 Weeks)
研究者
Nikhil Pai
Associate Professor, Division of Pediatric Gastroenterology & Nutrition
Hamilton Health Sciences Corporation