CompletedPhase 4

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

United States16 participantsStarted 2022-02-04

Plain-language 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.

Who can participate

Age range

13 Years – 17 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * 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 Exclusion Criteria: * 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.

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Right Anterior Insula GABA level

Timeframe: 8 weeks

Trial details

NCT IDNCT05063656

SponsorDavid Cochran

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2025-12-31

View on ClinicalTrials.gov More Autism Spectrum Disorder trials