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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
87

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
King's College London

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 12, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 12, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 27, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 10, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 20, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 22, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 19, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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