Exploring the Gut-Brain-Behavior Axis With Biomarkers, Probiotic Efficacy, and Artificial Intelligence Algorithms

Precision Health in Autism: Exploring the Gut-Brain-Behavior Axis With Biomarkers, Probiotic Efficacy, and Artificial Intelligence Algorithms

This groundbreaking human study on the ASD microbiome includes probiotic clinical trials, investigation of treatment biomarkers, machine learning/deep learning platform development for ASD classification and prediction, and identification of diagnostic biomarkers. Upon completion, the investigators anticipate publishing at least 12 SCI papers and/or patents and establishing an auxiliary diagnosis platform for both clinical and academic purposes. The findings will offer new insights into the pathogenetic mechanisms, improving early detection, diagnosis, and treatment, ultimately advancing precision medicine for ASD.

Study Overview

• Status: Recruiting
• Conditions: Autism Spectrum Disorder
• Intervention / Treatment: Other: probiotic (GKB7/placebo)

Detailed Description

With an increased prevalence of autism spectrum disorder (ASD) worldwide and in Taiwan, ASD demands urgent attention due to its lasting impact, unclear causes, and limited diagnostic and treatment options. Recent studies highlight disruptions in the gut-brain axis, particularly in ASD. Building on PI Gau's prior research on altered gut microbiota in autism spectrum disorder (ASD), this proposed 4-year study aims to develop evidence-based probiotic intervention (GKB7) and treatment biomarkers for behavioral interventions (Naturalistic Developmental Behavioral Interventions, NDBI, and Program for the Education and Enrichment of Relational Skills, PEERS®) through comprehensive assessments. The ultimate goal is to establish probiotic treatments and diagnostic/treatment biomarkers for ASD utilizing a deep-learning multimodal auxiliary platform.

Specific Aims:

S.I To conduct a randomized, double-blind, placebo-controlled trial to assess the treatment effects of Clostridium butyricum GKB7 on ASD.

S.II To investigate the effect of NDBI intervention trials using metagenomics as the outcome measure.

S.III To evaluate the effect of PEERS® interventional trials with metagenomics as the outcome measure.

S.IV To develop an artificial intelligence (machine/deep learning) multimodal auxiliary prediction platform that integrates environmental, behavioral/clinical, neurocognitive/imaging, and metagenomic data for ASD diagnosis, subtyping, and impairment prediction.

S.V To identify microbiome and metabolomic biomarkers and endophenotypes of ASD, and to establish Gut-Brain-Behavioral Axes in ASD.

• Study Type: Interventional
• Enrollment (Estimated): 110
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Susan Shur-Fen Gau, MD, PhD; Phone Number: 266802 +886-2-23123456; Email: gaushufe@ntu.edu.tw

Study Locations

• Taiwan
  • Taipei, Taiwan
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Susan Shur-Fen Gau, MD, PhD; Phone Number: 266802 + 886-2-23123456; Email: gaushufe@ntu.edu.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Children and adolescents aged 4 to 15 who are clinically diagnosed with ASD according to DSM-5 criteria and confirmed by the ADI-R/ADOS.
• Caregivers cooperate with all the assessments and stool and blood collection.

Exclusion Criteria:

• A history of major psychiatric disorders (e.g., schizophrenia, bipolar disorder, major depression), neurological disorders, and substances use disorders.
• Difficulty following instructions.
• Consumption of antibiotics and yogurt or probiotic products two weeks prior to enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: probiotic (GKB7/placebo); The objectives of this double-blind randomized placebo-controlled trial are to evaluate the tolerability, safety, and efficacy of the probiotic intervention with Clostridium butyricum GKB7 among 90 4-15-year-old children and adolescents with a clinical diagnosis of ASD according to the DSM-5
Experimental: GKB7	Other: probiotic (GKB7/placebo); The objectives of this double-blind randomized placebo-controlled trial are to evaluate the tolerability, safety, and efficacy of the probiotic intervention with Clostridium butyricum GKB7 among 90 4-15-year-old children and adolescents with a clinical diagnosis of ASD according to the DSM-5

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Global Impression	The CGI-S (Clinical Global Impression-Severity Scale) and CGI-I (-Improvement Scale) are single-item ratings of the clinician's assessment of the global severity of clinical symptoms. Severity and improvement are rated on a 7-point scale (from 1 = normal, not at all ill, to 7 = among the most extremely ill) and (from 1 = very much improved, to 7 = very much worse).	At baseline (before treatment, V0), month 1 (V1), month 2 (V2), month 3 (V3), month 4 (V4), and month 6 (V5)
Social Responsiveness Scale (SRS)	The SRS is a 65-item questionnaire based on parent-reports on the child's social interactions with others (rating 0-3), consists of 5 subscales: social awareness, social cognition, social communication, social motivation, and autistic mannerisms	At baseline (before treatment, V0), month 1 (V1), month 2 (V2), month 3 (V3), month 4 (V4), and month 6 (V5)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Self-administered questionnaires	The self-administered questionnaires include autistic symptoms (Autism Spectrum Quotient, AQ; Sensory Profile, SP), psychopathology (Child Behavior Checklist, CBCL; Swanson, Nolan, and Pelham, version IV scale, SNAP-IV), social functions/quality of life (Social Adjustment Inventory for Children and Adolescents, SAICA), and executive functions (Behavior Rating Inventories of Executive Function, BRIEF)	At baseline (before treatment, V0), month 3 (V3), and month 6 (V5)
Neuropsychological functions: Continuous Performance Test(CPT)	The 4 dimensions of CCPT: focused attention, hyperactivity/impulsivity, sustained attention, and vigilance	At baseline (before treatment, V0), month 3 (V3), and month 6 (V5)
Neuropsychological functions: Cambridge Neuropsychological Test Automated Batteries(CANTAB)	The 4 main cognitive components of CANTAB: Visual Memory, Attention, Working and Planning Memory (Executive Functions), and Decision Making	At baseline (before treatment, V0), month 3 (V3), and month 6 (V5)

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2024
• Primary Completion (Estimated): April 30, 2025
• Study Completion (Estimated): April 30, 2028

Study Registration Dates

• First Submitted: November 4, 2024
• First Submitted That Met QC Criteria: November 5, 2024
• First Posted (Estimated): November 7, 2024

Study Record Updates

• Last Update Posted (Estimated): November 7, 2024
• Last Update Submitted That Met QC Criteria: November 5, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder
• Other Study ID Numbers: 202404049RIPA

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No