Study Protocol for a Randomized Controlled of Fecal Microbiota Transplantation Via Different Routes in Children With Moderate-to-Severe Autism Spectrum Disorder
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Change in Total Score on the Childhood Autism Rating Scale (CARS)
研究概览
简要总结
This is a single-center, randomized, double-dummy, triple-blind, placebo-controlled, three-arm parallel-group superiority trial. The study aims to compare the efficacy and safety of Fecal Microbiota Transplantation (FMT) administered via two different invasive routes-nasojejunal tube (NJT) and colonoscopy-versus a placebo control in children aged 3-16 years with moderate-to-severe Autism Spectrum Disorder (ASD). A total of 75 participants will be randomized in a 1:1:1 ratio to receive either active FMT via NJT with sham colonoscopy, active FMT via colonoscopy with sham NJT, or placebo via both routes. All participants will continue their stable behavioral interventions throughout the study. The primary outcome is the change from baseline to Week 24 in the total score of the Childhood Autism Rating Scale (CARS). Secondary outcomes include changes in other behavioral and gastrointestinal symptom scores, gut microbiota profiling, and safety assessments over 48 weeks.
详细描述
Background:
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder often accompanied by gastrointestinal (GI) symptoms and gut microbiota dysbiosis. Fecal Microbiota Transplantation (FMT) has shown promise in modulating the gut-brain axis and improving both behavioral and GI symptoms in preliminary ASD studies. However, the optimal route of FMT administration remains unclear, and high-quality comparative evidence is lacking.
Objectives:
Primary: To compare the efficacy of FMT delivered via NJT versus colonoscopy versus placebo in improving social interaction and communication, as measured by the change in CARS total score from baseline to Week 24.
Secondary: To evaluate effects on social responsiveness (SRS), aberrant behaviors (ABC), sensory processing (SSP), sleep quality (CSHQ), GI symptoms (GSRS), gut microbiota engraftment dynamics, and safety/tolerability.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 3 Years 至 16 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 3-16 years.
- •Diagnosed with ASD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), with a Childhood Autism Rating Scale (CARS) total score ≥36 (moderate-to-severe autism).
- •Legal guardians fully comprehend the trial's informed consent and voluntarily provide written consent.
- •Compliance with follow-up visits, examinations, and specimen collection.
- •No probiotic supplements consumed within the preceding 3 months.
排除标准
- •Use of probiotics or prebiotics within 3 months prior to enrollment.
- •Antibiotic usage within 1 month prior to enrollment.
- •Presence of fever (axillary temperature ≥37.5°C).
- •Dependency on tube feeding.
- •Severe gastrointestinal conditions requiring immediate intervention (e.g., life-threatening intestinal obstruction, perforation, hemorrhage, ulcerative colitis, Crohn's disease, celiac disease, or eosinophilic esophagitis).
- •Diagnosis of severe malnutrition, underweight status (BMI-for-age <3rd percentile), or severe immunodeficiency disorders.
- •History of severe allergic reactions (e.g., anaphylaxis).
- •Monogenic disorders (e.g., Fragile X syndrome, Rett syndrome).
- •Comorbid psychiatric diagnoses, including depression, developmental speech/language disorders, intellectual disability, attention-deficit/hyperactivity disorder (ADHD), selective mutism, reactive attachment disorder, or childhood schizophrenia.
研究组 & 干预措施
Group 1 (FMT-NJT)
active FMT via nasojejunal tube + sham colonoscopy
干预措施: ctive FMT via Nasojejunal Tube (FMT-Upper GI) (Procedure)
Group 2 (FMT-C)
active FMT via colonoscopy with placement of a transendoscopic enteral tube (TET) secured at the cecum during the first session, followed by two subsequent infusions via the indwelling TET + sham nasojejunal intubation.
干预措施: Active FMT via Colonoscopy and Transendoscopic Tube (FMT-Lower GI) (Procedure)
Group 3 (Control)
placebo via nasojejunal tube + placebo via colonoscopy (sham procedures for both routes)
干预措施: Placebo via Sham Procedures (Sham-Control) (Procedure)
结局指标
主要结局
Change in Total Score on the Childhood Autism Rating Scale (CARS)
时间窗: Pre-FMT, 3 months post-FMT, and 6 months post-FMT
The change from baseline to Week 24 in the total score of the Childhood Autism Rating Scale (CARS). The CARS is a 15-item behavioral rating scale used to diagnose and assess the severity of autism. Each item is scored from 1 to 4. The total score ranges from 15 to 60. A higher score indicates more severe autism symptoms.
次要结局
- Change in Total Score on the Social Responsiveness Scale, Second Edition (SRS-2)(Pre-FMT, at Week 12, 24, and 48 post-FMT.)
- Change in Total Score on the Aberrant Behavior Checklist (ABC)(Pre-FMT, at Week 12, 24, and 48 post-FMT.)
- Change in Total Score on the Gastrointestinal Symptom Rating Scale (GSRS)(Pre-FMT, during FMT, and at 2, 6, 12, 24, and 48 post-FMT.)
- Daily Stool Record (DSR)(Pre-FMT, during FMT, and at 2, 6, 12, 24 and 48 weeks post-FMT.)
- Change in Total Score on the Short Sensory Profile (SSP)(Pre-FMT, at12, 24 and 48 post-FMT.)
- Change in Total Score on the Children's Sleep Habits Questionnaire (CSHQ)(Pre-FMT, at12, 24 and 48 post-FMT.)
- Change in Gut Microbiota Alpha Diversity (Shannon Index)(Pre-FMT, and at 2, 6, 12, 24 and 48 weeks post-FMT.)
- Change in Relative Abundance of Specific Gut Microbial Taxa (at the genus level)(Pre-FMT, and at 2, 6, 12, 24 and 48 weeks post-FMT.)
- Incidence of Treatment-Emergent Adverse Events (TEAEs)(From date of randomization until the end of study visit (Week 48).)
- Incidence of Serious Adverse Events (SAEs)(From date of randomization until the end of study visit (Week 48).)
研究者
Dongling Dai
Professor
Shenzhen Children's Hospital