Study of Neuroimaging Biomarkers of Social Cognition Deficits in Adolescents (Age 13-17) With Autism Spectrum Disorder and Effects of Gabapentin

NCT03589898 | Completed Early Phase 1 FDA Drug

• 2 other identifiers: H000126561K23MH113008-01A1
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that is increasing in prevalence, and is characterized by deficits in social communication and interaction across multiple contexts, and restricted, repetitive patterns of behavior, interests, or activities. The majority of individuals with ASD have poor outcomes in the area of social functioning; however, there are no medical treatments available that target the core social communication deficits. The goal of the proposed research is to understand the neurobiological role of an imbalance in excitatory (glutamate) and inhibitory (gamma-aminobutyric acid, GABA) neurotransmission in the social cognition deficits in ASD, and to develop proton magnetic resonance spectroscopy as a measurement of target engagement to measure the ability of a medication, gabapentin, to increase cortical GABA levels. Spectrally-edited proton magnetic resonance spectroscopy (1H-MRS) provides an ideal method for measuring cortical GABA levels. All proposed studies will be in 70 adolescents (male and female) with ASD (age 13 to 17 years). Specific Aim 1: To measure correlations of 1H-MRS GABA levels in the anterior cingulate cortex (ACC) and occipital cortex (OC) with clinical measures of social cognition at baseline. Specific Aim 2: To measure the effect of an initial one time dose of gabapentin on 1H-MRS GABA levels in the ACC and OC. The hypotheses are 1) that higher social cognition ability will be positively correlated with GABA in the ACC but not in the OC (a control, non-social cognition-related region) of individuals with ASD, and 2) that gabapentin will increase GABA levels in the ACC and OC of youth with ASD.

Conditions

Autism Spectrum Disorder

Keywords

magnetic resonance imaging; spectroscopy; GABA; glutamate; social cognition

Outcome Measures

Primary Outcomes (2)

• Cortical GABA in Anterior Cingulate Cortex

  Cortical gamma-aminobutyric acid levels measured using magnetic resonance spectroscopy with voxel placed in bilateral anterior cingulate cortex

  6 hours post-administration

• Cortical GABA in Right Anterior Insula

  Cortical gamma-aminobutyric acid levels measured using magnetic resonance spectroscopy with voxel placed in right anterior insula

  6 hours post-administration

Secondary Outcomes (2)

• Cortical Glx in Anterior Cingulate Cortex

  6 hours post-administration

• Cortical Glx in Right Anterior Insula

  6 hours post-administration

Study Arms (1)

Gabapentin

EXPERIMENTAL

Single dose of gabapentin 900 mg will be given and neuroimaging markers will be measured before and after administration of gabapentin

Drug: Gabapentin

Interventions

Gabapentin DRUG

Single dose of gabapentin 900 mg

Gabapentin

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).

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.)
• Preterm (\<36 weeks)
• Failure to thrive within first year of life
• Contraindications for MRI, such as metallic or electronic implants in the body, or severe claustrophobia
• History of head trauma with loss of consciousness for more than 30 minutes
• Unstable psychiatric illness, history of psychotic disorder, or psychiatric illness 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 at screening as assessed by the Columbia Suicide Severity Rating Scale
• IQ \< 70
• History of intolerance to gabapentin or pregabalin
• Current substance use (including nicotine)
• Pregnancy at time of 1H-MRS or gabapentin administration
• Current treatment with gabapentin

Sponsors & Collaborators

• University of Massachusetts, Worcester: lead
• National Institute of Mental Health (NIMH): collaborator
• Johns Hopkins University: 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, PhD

  University of Massachusetts, Worcester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Psychiatry and Pediatrics

Study Record Dates

• First Submitted: July 6, 2018
• First Posted: July 18, 2018
• Study Start: September 14, 2017
• Primary Completion: August 31, 2022
• Study Completion: August 31, 2022
• Last Updated: November 2, 2022

Record last verified: 2022-10

Locations

US (1)