Modulation of the Brain Excitatory/Inhibitory (E/I) Balance in Autism Spectrum Disorder (ASD)

NCT ID: NCT03594552

Last Updated: 2022-11-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 87 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-01
• Study Completion Date: 2020-03-12

Brief Summary

This study investigates the brain response to a single acute dose of Arbaclofen, the R-enantiomer of the GABA-B agonist Baclofen, compared to a single dose of placebo in healthy men with and without autism spectrum disorder.

Detailed Description

Previous research suggests that GABAergic drug compounds could shift brain excitation and inhibition (E-I) in the healthy brain and in neurodevelopmental psychiatric conditions, such as autism spectrum disorder (ASD) - where this balance is disrupted. A study by Ajram et al. (2017) has shown an E-I shifted towards more GABA in individuals with ASD, and not in controls, after a single dose of the anti-glutamatergic and pro-GABAergic drug Riluzole. Moreover, brain connectivity patterns in ASD patients where shifted towards the ones observed in the control group. However, it was unclear whether this changes could be driven by GABA receptors, thus more specific probes may help to clarify the mechanism underlying the E-I coordination in ASD. Therefore, this study will use neuroimaging and electrophysiology to investigate the brain E-I coordination in ASD compared to control participants when the system is responding to a single dose of the specific GABA-B (STX209) receptor agonist. 50 adult individuals with ASD and 50 neurotypical adults (25 males and 25 females per group) will be invited to participate. Each participant will receive a single dose of the drug (15mg or 30mg Arbaclofen) or matched placebo). Brain activity and neurochemistry will be investigated using magnetic resonance imaging. Further data will be collected through questionnaires, behavioural tasks, blood samples, and sensory tasks using electroencephalography and retinal imaging.

Conditions

Autism Spectrum Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Placebo, Arbaclofen_15, Arbaclofen_30

Dose order: Placebo, Arbaclofen 15mg, Arbaclofen 30mg

Group Type: EXPERIMENTAL

Arbaclofen_15

Intervention Type: DRUG

Single oral dose (15mg)

Arbaclofen_30

Intervention Type: DRUG

Single oral dose (30mg)

Placebo

Intervention Type: DRUG

Single oral dose placebo (oral tablet)

Placebo, Arbaclofen_30, Arbaclofen_15

Dose order: Placebo, Arbaclofen 30mg, Arbaclofen 15 mg

Group Type: EXPERIMENTAL

Arbaclofen_15

Intervention Type: DRUG

Single oral dose (15mg)

Arbaclofen_30

Intervention Type: DRUG

Single oral dose (30mg)

Placebo

Intervention Type: DRUG

Single oral dose placebo (oral tablet)

Arbaclofen_30, Placebo, Arbaclofen_15

Dose order: Arbaclofen 30mg, Placebo, Arbaclofen 15mg

Group Type: EXPERIMENTAL

Arbaclofen_15

Intervention Type: DRUG

Single oral dose (15mg)

Arbaclofen_30

Intervention Type: DRUG

Single oral dose (30mg)

Placebo

Intervention Type: DRUG

Single oral dose placebo (oral tablet)

Arbaclofen_15, Placebo, Arbaclofen_30

Dose order: Arbaclofen 15mg, Placebo, Arbaclofen 30mg

Group Type: EXPERIMENTAL

Arbaclofen_15

Intervention Type: DRUG

Single oral dose (15mg)

Arbaclofen_30

Intervention Type: DRUG

Single oral dose (30mg)

Placebo

Intervention Type: DRUG

Single oral dose placebo (oral tablet)

Arbaclofen_15, Arbaclofen_30, Placebo

Dose order: Arbaclofen 15mg, Arbaclofen 30mg, Placebo

Group Type: EXPERIMENTAL

Arbaclofen_15

Intervention Type: DRUG

Single oral dose (15mg)

Arbaclofen_30

Intervention Type: DRUG

Single oral dose (30mg)

Placebo

Intervention Type: DRUG

Single oral dose placebo (oral tablet)

Arbaclofen_30, Arbaclofen_15, Placebo

Dose order: Arbaclofen 30mg, Arbaclofen 15mg, Placebo

Group Type: EXPERIMENTAL

Arbaclofen_15

Intervention Type: DRUG

Single oral dose (15mg)

Arbaclofen_30

Intervention Type: DRUG

Single oral dose (30mg)

Placebo

Intervention Type: DRUG

Single oral dose placebo (oral tablet)

Interventions

Arbaclofen_15

Single oral dose (15mg)

Intervention Type: DRUG

Arbaclofen_30

Single oral dose (30mg)

Intervention Type: DRUG

Placebo

Single oral dose placebo (oral tablet)

Intervention Type: DRUG

Other Intervention Names

r-baclofen, STX209; r-baclofen, STX209; Placebo oral tablet

Eligibility Criteria

Inclusion Criteria

• ASD participants must pass diagnostic threshold for ASD on the Autism Diagnostic Interview-Revised (if and informant is available)
• ASD participants must be currently symptomatic on Autism Diagnostic Observation Schedule (ADOS)
• Age 18-60 years
• Can give informed consent
• medication free in the month preceding participation; but regular medication (used in a stable dose over the two months previous to participation) with drug which does not affect glutamate or GABA directly may be permitted
• IQ>70

Exclusion Criteria

• IQ<70
• history of psychosis, co-morbid major mental illness, significant physical illness (heart disease, high blood pressure, seizures) habitual substance misuse (including alcohol)
• ASD caused by a known genetic syndrome e.g. Fragile X or 22q11 deletion syndrome,
• past/present treatment for epilepsy
• Change of medication dose/start of a new pharmacological therapy in the month prior to participation

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

King's College London

OTHER

Sponsor Role: lead

Responsible Party

Dr Grainne McAlonan

Deputy head of department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Grainne McAlonan, PhD

Role: PRINCIPAL_INVESTIGATOR

King's College London

Locations

King's College London

London, , United Kingdom

Countries

United Kingdom

Other Identifiers

HR16-17 4081

Identifier Type: -

Identifier Source: org_study_id