Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
Status:
Not yet recruiting
Trial end date:
2023-11-01
Target enrollment:
Participant gender:
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.