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

November 19, 2022 updated by: Dr Grainne McAlonan, King's College London

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

87

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • London, United Kingdom, SE5 8AF
        • King's College London

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Placebo, Arbaclofen_15, Arbaclofen_30
Dose order: Placebo, Arbaclofen 15mg, Arbaclofen 30mg
Drug: Arbaclofen_15
Single oral dose (15mg)
Other Names:
  • r-baclofen, STX209
Drug: Arbaclofen_30
Single oral dose (30mg)
Other Names:
  • r-baclofen, STX209
Drug: Placebo
Single oral dose placebo (oral tablet)
Other Names:
  • Placebo oral tablet
Experimental: Placebo, Arbaclofen_30, Arbaclofen_15
Dose order: Placebo, Arbaclofen 30mg, Arbaclofen 15 mg
Drug: Arbaclofen_15
Single oral dose (15mg)
Other Names:
  • r-baclofen, STX209
Drug: Arbaclofen_30
Single oral dose (30mg)
Other Names:
  • r-baclofen, STX209
Drug: Placebo
Single oral dose placebo (oral tablet)
Other Names:
  • Placebo oral tablet
Experimental: Arbaclofen_30, Placebo, Arbaclofen_15
Dose order: Arbaclofen 30mg, Placebo, Arbaclofen 15mg
Drug: Arbaclofen_15
Single oral dose (15mg)
Other Names:
  • r-baclofen, STX209
Drug: Arbaclofen_30
Single oral dose (30mg)
Other Names:
  • r-baclofen, STX209
Drug: Placebo
Single oral dose placebo (oral tablet)
Other Names:
  • Placebo oral tablet
Experimental: Arbaclofen_15, Placebo, Arbaclofen_30
Dose order: Arbaclofen 15mg, Placebo, Arbaclofen 30mg
Drug: Arbaclofen_15
Single oral dose (15mg)
Other Names:
  • r-baclofen, STX209
Drug: Arbaclofen_30
Single oral dose (30mg)
Other Names:
  • r-baclofen, STX209
Drug: Placebo
Single oral dose placebo (oral tablet)
Other Names:
  • Placebo oral tablet
Experimental: Arbaclofen_15, Arbaclofen_30, Placebo
Dose order: Arbaclofen 15mg, Arbaclofen 30mg, Placebo
Drug: Arbaclofen_15
Single oral dose (15mg)
Other Names:
  • r-baclofen, STX209
Drug: Arbaclofen_30
Single oral dose (30mg)
Other Names:
  • r-baclofen, STX209
Drug: Placebo
Single oral dose placebo (oral tablet)
Other Names:
  • Placebo oral tablet
Experimental: Arbaclofen_30, Arbaclofen_15, Placebo
Dose order: Arbaclofen 30mg, Arbaclofen 15mg, Placebo
Drug: Arbaclofen_15
Single oral dose (15mg)
Other Names:
  • r-baclofen, STX209
Drug: Arbaclofen_30
Single oral dose (30mg)
Other Names:
  • r-baclofen, STX209
Drug: Placebo
Single oral dose placebo (oral tablet)
Other Names:
  • Placebo oral tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Neurochemical response to GABAergic stimulation.
Time Frame: Through study completion, an average of 2 years.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Functional connectivity measures using resting state functional magnetic resonance imaging.
Time Frame: Through study completion, an average of 2 years.
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.
Brain oscillations under sensory stimulation
Time Frame: Through study completion, an average of 2 years.
Brain oscillations and event-related potentials will be recorded during sensory stimulation using high density electroencephalography.
Through study completion, an average of 2 years.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

King's College London

Investigators

  • Principal Investigator: Grainne McAlonan, PhD, King's College London

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2018

Primary Completion (Actual)

March 12, 2020

Study Completion (Actual)

March 12, 2020

Study Registration Dates

First Submitted

June 27, 2018

First Submitted That Met QC Criteria

July 10, 2018

First Posted (Actual)

July 20, 2018

Study Record Updates

Last Update Posted (Actual)

November 22, 2022

Last Update Submitted That Met QC Criteria

November 19, 2022

Last Verified

November 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HR16-17 4081

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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