Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin

NCT05063656 | Completed Phase 4 DMC FDA Drug

• 1 other identifier: STUDY00000151
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The social cognitive deficits associated with autism spectrum disorder (ASD) are related to an imbalance in excitatory and inhibitory neurotransmission, specifically a deficit in the inhibitory neurotransmitter GABA. The investigators have used magnetic resonance spectroscopy (MRS) techniques to measure GABA in specific brain regions and have demonstrated that a single dose of gabapentin increases GABA in brain regions associated with social cognition. This study will use a biomarker-driven approach to investigate gabapentin to correct the underlying imbalance of neurotransmitters and improve the core social cognitive deficits in ASD. By using a brain-based biomarker (GABA) that is quantifiable and measurable, the investigators can target this biomarker directly and measure the impact of the treatment. This will help with the future development of targeted therapies for ASD and provide an early marker of response to aid in the selection of individuals more likely to respond to various treatments. The specific aims of this study are to: 1) determine if treatment with gabapentin sustainably increases GABA in the right anterior insula (RAI; an area of the brain involved in social cognition), 2) determine if response of RAI GABA levels to a single dose challenge of gabapentin predicts a sustained response after treatment, and 3) determine if the increase in GABA levels with gabapentin treatment translates into clinically measurable improvement in social cognition. The investigators will conduct an 8-week open-label clinical trial of gabapentin in 40 adolescents (age 13-17 years) with ASD, using MRS before and after treatment to measure GABA in the RAI (the primary outcome for the study). Before the trial, a single dose challenge of gabapentin will be used to evaluate the immediate response of GABA levels in the RAI, to determine if this predicts later response. A secondary outcome will be the clinical effects of gabapentin on social cognition. This study can demonstrate for the first time that neuroimaging biomarkers can be used to guide treatment of social cognition deficits seen in ASD and that the excitatory-inhibitory imbalance in neurotransmitters in ASD can be pharmacologically targeted. This can provide a rational basis for pharmacological treatment of the core social deficits of ASD, providing direct benefit to participants in the study as well as indirect benefit to countless patients in the future.

Conditions

Autism Spectrum Disorder

Keywords

social cognition; GABA; gabapentin; magnetic resonance spectroscopy

Outcome Measures

Primary Outcomes (1)

• Right Anterior Insula GABA level

  Cortical GABA Levels in right anterior insula as measured by magnetic resonance spectroscopy

  8 weeks

Study Arms (1)

Gabapentin Open-label treatment

EXPERIMENTAL

8-week treatment with gabapentin

Drug: Gabapentin

Interventions

Gabapentin DRUG

8 weeks of gabapentin, titrated up to 20 mg/kg in 3 divided doses daily

Gabapentin Open-label treatment

Eligibility Criteria

• Age: 13 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age 13-17 years
• English as primary language (both child and legal guardian)
• DSM-5 criteria for Autism Spectrum Disorder
• IQ \>70 per Weschler Abbreviated Scale of Intelligence (WASI)
• Informed assent for the study (The guardian must also give written informed consent)
• For sexually active females, agreement to use two forms of contraception during trial to avoid pregnancy

You may not qualify if:

• Any neurological disorder (e.g., cerebral palsy, fetal alcohol syndrome, cerebral neoplasm, bacterial meningitis, epilepsy, etc.)
• Genetic disorders (e.g., Fragile X, Rett Syndrome, etc.)
• Contraindications for MRI, such as metallic or electronic implants in the body, or severe claustrophobia
• Unstable psychiatric disorder expected to require psychotropic medication changes over the course of the study
• History of psychotic disorder
• Any condition that would prevent the subject from being able to complete study protocol
• Unstable medical illness such as diabetes, asthma, thyroid disease
• Currently on medications that cause respiratory depression, e.g. opioids, benzodiazepines
• Clinically significant suicidal ideation as assessed by the Columbia Suicide Severity Rating Scale
• History of intolerance to gabapentin or pregabalin
• Current substance use (including nicotine)
• Current treatment with gabapentin
• History of renal dysfunction
• Pregnancy in female participants.

Sponsors & Collaborators

• David Cochran: lead
• Eagles Autism Foundation: collaborator

Study Sites (1)

University of Massachusetts Medical School

Worcester, Massachusetts, 01655, United States

Location

MeSH Terms

Conditions

Autism Spectrum Disorder

Interventions

Gabapentin

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Amines; Organic Chemicals; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• David Cochran, MD

  UMass Medical School

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Psychiatry and Pediatrics

Model Details: Open-label treatment with gabapentin for 8 weeks

Study Record Dates

• First Submitted: September 21, 2021
• First Posted: October 1, 2021
• Study Start: February 4, 2022
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: February 20, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: 6 months after publication
• Access Criteria: Available upon request from primary contact person

Locations

US (1)