Efficacy of Bumetanide in Children With Autism Spectrum Disorder Guided by Peripheral Blood Biomarkers and Machine Learning Models

Fei Li

Status and phase: Enrolling; Phase 2

Conditions: Autism Spectrum Disorder

Treatments: Drug: Bumetanide; Behavioral: Treatment as usual (TAU)

Study type: Interventional

Funder types: Other

Identifiers

NCT07005414

XHEC-C-2025-089

Details and patient eligibility

About

The objective of this study is to learn if bumetanide could alleviate the clinical symptoms in children with autism spectrum disorder (ASD), who has been predicted as high responders to bumetanide via a cytokine-based predictive model. The Eligible ASD participants identified as high responder to bumetanide will be randomly assigned to either the experimental group or the control group. Participants in the experimental group will receive bumetanide interventions, along with the behavioral interventions, for three months. Participants in the control group will only undergo behavioral interventions. The clinical symptoms and potential adverse effects will be closely monitored throughout the intervention period.

Full description

Autism spectrum disorder (ASD) affects about 1% children around the world and can cause lifelong disability and elevate premature mortality. Currently, no medication that can cure ASD or its core symptoms. The recent success of repurposing drugs for novel treatments in psychiatry has been highlighted, with one of the examples given being the use of bumetanide to improve the core symptoms in ASD. However, the heterogeneity in the treatment effect of bumetanide among ASD patients has been observed. A further study (Li et al., Translational Psychiatry, 2022) demonstrated that integrating the cytokine levels and behavioral symptoms could help to identify optimal responders to bumetanide in ASD, showing promise for biomarker- and machine learning model-guided precision medicine with bumetanide.

This open-label clinical trial aimed at investigating whether bumetanide could alleviate the clinical symptoms in children with ASD predicted as high responders to bumetanide via a cytokine-based predictive model. The Eligible ASD participants identified as high responder to bumetanide will be randomly assigned to either the experimental group or the control group. Participants in the experimental group will receive bumetanide interventions, along with the behavioral interventions, for a period of three months. Participants in the control group will only undergo behavioral interventions. The clinical symptoms and potential adverse effects will be closely monitored throughout the intervention period.

Enrollment: 66 estimated patients

Sex: All

Ages: 3 to 6 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Children aged between 3 and 6 years old
• Meeting the ASD diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)
• Meeting the ASD diagnostic criteria of the Diagnostic Observational Scale for Autism, Second Edition(ADOS-2)
• CARS total score ≥ 30
• Identified as high responder to bumetanide by machine learning algorithms
• Obtaining informed consent from the legal guardian

Exclusion criteria

• Liver and kidney dysfunction
• With a history of allergy to sulfa drugs
• History of neurological diseases such as epilepsy
• Abnormal ECG
• Diagnosed with genetic or chromosomal abnormalities
• Brain structural abnormalities detected by MRI which required surgical intervention
• Using the melatonin treatment for sleep disorders or withdrawal less than three weeks.
• Received any new intervention within 8 weeks prior to enrollment

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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66 participants in 2 patient groups

bumetanide plus treatment as usual (TAU)

Experimental group

Description:

Participants in experimental group will receive bumetanide, along with treatments as usual (i.e. behavioral interventions)

Treatment:

Behavioral: Treatment as usual (TAU)

Drug: Bumetanide

Treatment as usual (TAU)

Other group

Description:

Participants will undergo treatment as usual, such as behavioral interventions

Treatment:

Behavioral: Treatment as usual (TAU)