NCT07381374

Fecal Microbiota Transplantation in Children With ASD

Study Protocol for a Randomized Controlled of Fecal Microbiota Transplantation Via Different Routes in Children With Moderate-to-Severe Autism Spectrum Disorder

• Status: Not Yet Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 75 (estimated)
• Sponsor: Shenzhen Children's Hospital · Other Government
• Sex: All
• Age: 3 Years – 16 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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. Methods: Design: Single-center, randomized, double-dummy, triple-blind, placebo-controlled, three-arm parallel-group trial. Participants: 75 children aged 3-16 years with DSM-5-confirmed moderate-to-severe ASD (CARS ≥36) and stable behavioral intervention. Interventions: Group 1 (FMT-NJT): Active FMT via NJT + sham colonoscopy. Group 2 (FMT-C): Active FMT via colonoscopy with placement of a transendoscopic enteral tube (TET) in the cecum for subsequent infusions + sham NJT. Group 3 (Control): Placebo via both NJT and colonoscopy (sham procedures). Dosage: 5 mL/kg (max 100 mL) per infusion, administered every other day for three sessions. Blinding: Triple-blind-participants/guardians, outcome assessors, and data analysts are blinded. An independent pharmacy unit prepares identical active and placebo preparations. Assessments: Behavioral scales (CARS, SRS, ABC, SSP, CSHQ), GI symptoms (GSRS), stool metagenomics, and safety monitoring at baseline, Weeks 2, 6, 12, 24, and 48. Sample Size: 25 per group (total N=75), calculated to detect a 2.5-point difference in CARS change with 80% power, accounting for 15% dropout. Randomization: Centralized block randomization stratified by age and baseline CARS severity. Statistical Analysis: ANCOVA for primary outcome with baseline adjustment; mixed models for repeated measures; descriptive and inferential methods for secondary and safety outcomes. Outcomes: Primary: Change in CARS total score from baseline to Week 24. Secondary: Changes in SRS, ABC, GSRS, SSP, CSHQ scores; microbiota composition/function; incidence and severity of adverse events (CTCAE v5.0). Significance: This trial will provide high-level evidence on whether the therapeutic effect of FMT in ASD depends on the gastrointestinal delivery site. The novel TET-based protocol for repeated cecal delivery allows for a rigorous comparison of microbial engraftment in the lower versus upper GI tract. The results will guide the optimization of microbiota-targeted therapies for ASD and other conditions linked to the gut-brain axis.

Conditions

• Autism Spectrum Disorder

Interventions

Type	Name	Description
PROCEDURE	ctive FMT via Nasojejunal Tube (FMT-Upper GI)	Intervention: Active FMT via Nasojejunal Tube (FMT-Upper GI) Intervention Type: Procedure + Biological Intervention Name: Upper Gastrointestinal-Targeted Fecal Microbiota Transplantation Description: Participants in this group receive active fecal microbiota suspension delivered to the jejunum (upper gastrointestinal tract). Under endoscopic guidance, a nasojejunal tube is placed with its tip positioned past the Ligament of Treitz. The active FMT preparation is then infused slowly through this tube. Additionally, participants undergo a sham colonoscopy (simulated procedure under anesthesia where the scope is inserted to the rectosigmoid junction with minimal water/air insufflation, but no FMT is administered). Dosage: 5 mL per kilogram of body weight, with a maximum total volume of 100 mL per infusion. Frequency: Administered once every other day, for a total of three sessions over 5 days.
PROCEDURE	Active FMT via Colonoscopy and Transendoscopic Tube (FMT-Lower GI)	Participants in this group receive active fecal microbiota suspension delivered to the cecum (lower gastrointestinal tract). The intervention involves two phases: First Session (Day 0): Under general anesthesia, a full colonoscopy is performed to reach the cecum. The active FMT preparation is infused directly into the cecum. Subsequently, a transendoscopic enteral tube (TET) is advanced through the colonoscope and its tip is secured in the cecum using endoscopic clips. Second \& Third Sessions (Days 2 \& 4): The active FMT preparation is infused through the indwelling TET at the bedside, without the need for repeat colonoscopy or general anesthesia. Additionally, participants undergo a sham nasojejunal intubation (a tube is placed into the stomach and secured, and a placebo is infused). Dosage: 5 mL per kilogram of body weight, with a maximum total volume of 100 mL per infusion. Frequency: Administered once every other day, for a total of three sessions over 5 days.
PROCEDURE	Placebo via Sham Procedures (Sham-Control)	Participants in this control group undergo both sham procedures with infusion of an inactivated placebo suspension, which is visually and physically identical to the active FMT preparation but contains no viable microbiota. Sham Nasojejunal Intubation: A tube is placed into the stomach (not the jejunum) and secured. The placebo suspension is infused. Sham Colonoscopy: Under anesthesia, a simulated colonoscopy is performed (scope inserted to rectosigmoid junction with minimal insufflation). No substance is infused during this sham procedure. This double-sham design ensures that both potential delivery routes are "simulated" for the control group. Dosage: Volume-matched to the active FMT arms (5 mL/kg, max 100 mL) for the nasogastric infusion. No infusion during sham colonoscopy. Frequency: The placebo infusion (during sham NJ intubation) occurs once every other day, for a total of three sessions over 5 days, coinciding with the two sham procedures.

Timeline

• Start date: 2026-02-01
• Primary completion: 2026-12-31
• Completion: 2027-04-12
• First posted: 2026-02-02
• Last updated: 2026-02-05