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

• Status: Recruiting
• Trial end date: 2022-08-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Massachusetts, Worcester
• Collaborators: Johns Hopkins University; National Institute of Mental Health (NIMH)
• Treatments: Gabapentin; gamma-Aminobutyric Acid

Criteria

Inclusion Criteria:

1. Age 13-17 years

2. English as primary language (both child and legal guardian)

3. DSM-5 criteria for Autism Spectrum Disorder

4. IQ >70 per Weschler Abbreviated Scale of Intelligence (WASI)

5. Informed assent for the study (The guardian must also give written informed consent).

Exclusion Criteria:

1. Any neurological disorder (e.g., cerebral palsy, fetal alcohol syndrome, cerebral neoplasm, bacterial meningitis, epilepsy, etc.)

2. Genetic disorders (e.g., Fragile X, Rett Syndrome, etc.)

3. Preterm (<36 weeks)

4. Failure to thrive within first year of life

5. Contraindications for MRI, such as metallic or electronic implants in the body, or severe claustrophobia

6. History of head trauma with loss of consciousness for more than 30 minutes

7. Unstable psychiatric illness, history of psychotic disorder, or psychiatric illness that would prevent the subject from being able to complete study protocol

8. Unstable medical illness such as diabetes, asthma, thyroid disease.

9. Currently on medications that cause respiratory depression, e.g. opioids, benzodiazepines

10. Clinically significant suicidal ideation at screening as assessed by the Columbia Suicide Severity Rating Scale

11. IQ < 70

12. History of intolerance to gabapentin or pregabalin

13. Current substance use (including nicotine)

14. Pregnancy at time of 1H-MRS or gabapentin administration

15. Current treatment with gabapentin

16. History of Renal Dysfunction

17. Subjects who weigh less than 36 kg

18. Subjects who weigh more than 105.8 kg