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

NCT03594552 | Completed

• 1 other identifier: HR16-17 4081
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 1

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.

Conditions

Autism Spectrum Disorder

Keywords

Autism Spectrum Disorder; Arbaclofen; E-I balance; pharmacological imaging; GABA

Outcome Measures

Primary Outcomes (1)

• Neurochemical response to GABAergic stimulation.

  Comparing brain excitation-inhibition measures (i.e., glutamate and GABA) when the GABAergic system is activated by a single oral dose of the GABA-B drug Arbaclofen versus the placebo condition.

  Through study completion, an average of 2 years.

Secondary Outcomes (2)

• Functional connectivity measures using resting state functional magnetic resonance imaging.

  Through study completion, an average of 2 years.

• Brain oscillations under sensory stimulation

  Through study completion, an average of 2 years.

Study Arms (6)

Placebo, Arbaclofen_15, Arbaclofen_30

EXPERIMENTAL

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

Drug: Arbaclofen_15; Drug: Arbaclofen_30; Drug: Placebo

Placebo, Arbaclofen_30, Arbaclofen_15

EXPERIMENTAL

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

Drug: Arbaclofen_15; Drug: Arbaclofen_30; Drug: Placebo

Arbaclofen_30, Placebo, Arbaclofen_15

EXPERIMENTAL

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

Drug: Arbaclofen_15; Drug: Arbaclofen_30; Drug: Placebo

Arbaclofen_15, Placebo, Arbaclofen_30

EXPERIMENTAL

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

Drug: Arbaclofen_15; Drug: Arbaclofen_30; Drug: Placebo

Arbaclofen_15, Arbaclofen_30, Placebo

EXPERIMENTAL

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

Drug: Arbaclofen_15; Drug: Arbaclofen_30; Drug: Placebo

Arbaclofen_30, Arbaclofen_15, Placebo

EXPERIMENTAL

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

Drug: Arbaclofen_15; Drug: Arbaclofen_30; Drug: Placebo

Interventions

Arbaclofen_15 DRUG

Single oral dose (15mg)

Also known as: r-baclofen, STX209

Arbaclofen_15, Arbaclofen_30, Placebo; Arbaclofen_15, Placebo, Arbaclofen_30; Arbaclofen_30, Arbaclofen_15, Placebo; Arbaclofen_30, Placebo, Arbaclofen_15; Placebo, Arbaclofen_15, Arbaclofen_30; Placebo, Arbaclofen_30, Arbaclofen_15

Arbaclofen_30 DRUG

Single oral dose (30mg)

Also known as: r-baclofen, STX209

Arbaclofen_15, Arbaclofen_30, Placebo; Arbaclofen_15, Placebo, Arbaclofen_30; Arbaclofen_30, Arbaclofen_15, Placebo; Arbaclofen_30, Placebo, Arbaclofen_15; Placebo, Arbaclofen_15, Arbaclofen_30; Placebo, Arbaclofen_30, Arbaclofen_15

Placebo DRUG

Single oral dose placebo (oral tablet)

Also known as: Placebo oral tablet

Arbaclofen_15, Arbaclofen_30, Placebo; Arbaclofen_15, Placebo, Arbaclofen_30; Arbaclofen_30, Arbaclofen_15, Placebo; Arbaclofen_30, Placebo, Arbaclofen_15; Placebo, Arbaclofen_15, Arbaclofen_30; Placebo, Arbaclofen_30, Arbaclofen_15

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• King's College London: lead

Study Sites (1)

King's College London

London, SE5 8AF, United Kingdom

Location

MeSH Terms

Conditions

Autism Spectrum Disorder

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Study Officials

• Grainne McAlonan, PhD

  King's College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Participants and investigators were blinded to the drug condition
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Deputy head of department

Model Details: Repeated-measures cross-over study, where each subject received each one of the three pharmacological probes in separate visits (i.e., placebo, arbaclofen low dose and arbaclofen high dose), with the order of tablet administration being pseudorandomized.

Study Record Dates

• First Submitted: June 27, 2018
• First Posted: July 20, 2018
• Study Start: February 1, 2018
• Primary Completion: March 12, 2020
• Study Completion: March 12, 2020
• Last Updated: November 22, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)