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

Autism Spectrum Disorder Clinical Trial

Official title:

Modulation of the Brain Excitatory/Inhibitory (E/I) Balance Through Neuronal and Glial Systems in Autism Spectrum Disorder (ASD

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03594552
• Other study ID #: HR16-17 4081
• Status: Completed
• Phase: N/A
• Start date: February 1, 2018
• Est. completion date: March 12, 2020

Study information

• Verified date: November 2022
• Source: King's College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 87
• Est. completion date: March 12, 2020
• Est. primary completion date: March 12, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Autism Spectrum Disorder
• Autistic Disorder
• Child Development Disorders, Pervasive
• Disease

Intervention

Drug:
• Arbaclofen_15
Single oral dose (15mg)
• Arbaclofen_30
Single oral dose (30mg)
• Placebo
Single oral dose placebo (oral tablet)

Locations

Country	Name	City	State
United Kingdom	King's College London	London

Sponsors (1)

Lead Sponsor	Collaborator
King's College London

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Functional connectivity measures using resting state functional magnetic resonance imaging.	Maps of functional connectivity will be obtained for each condition and compared between adults with and without ASD.	Through study completion, an average of 2 years.
Secondary	Brain oscillations under sensory stimulation	Brain oscillations and event-related potentials will be recorded during sensory stimulation using high density electroencephalography.	Through study completion, an average of 2 years.