Autism Spectrum DisorderNCT03594552
Modulation of the Brain Excitatory/Inhibitory (E/I) Balance in Autism Spectrum Disorder (ASD)
A study testing Arbaclofen_15 and Arbaclofen_30 in people with Autism Spectrum Disorder, run by King's College London at 1 site in United Kingdom.
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. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Autism Spectrum Disorder
- What is being tested?
- Arbaclofen_15 and Arbaclofen_30
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 87 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Feb 2018to 12 Mar 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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
- Being tested
- Arbaclofen_15, Arbaclofen_30, Placebo
- Keywords
- Autism Spectrum Disorder, Arbaclofen, E-I balance, pharmacological imaging, GABA
- Medical subject headings
- Autism Spectrum Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Arbaclofen_15Drug
Also called r-baclofen, STX209
Single oral dose (15mg)
Arbaclofen_30Drug
Also called r-baclofen, STX209
Single oral dose (30mg)
PlaceboDrug
Also called Placebo oral tablet
Single oral dose placebo (oral tablet)
| Study group | Role | What they receive |
|---|---|---|
| Placebo, Arbaclofen_15, Arbaclofen_30 | Experimental | Dose order: Placebo, Arbaclofen 15mg, Arbaclofen 30mg Receives: Drug: Arbaclofen_15; Drug: Arbaclofen_30; Drug: Placebo |
| Placebo, Arbaclofen_30, Arbaclofen_15 | Experimental | Dose order: Placebo, Arbaclofen 30mg, Arbaclofen 15 mg Receives: Drug: Arbaclofen_15; Drug: Arbaclofen_30; Drug: Placebo |
| Arbaclofen_30, Placebo, Arbaclofen_15 | Experimental | Dose order: Arbaclofen 30mg, Placebo, Arbaclofen 15mg Receives: Drug: Arbaclofen_15; Drug: Arbaclofen_30; Drug: Placebo |
| Arbaclofen_15, Placebo, Arbaclofen_30 | Experimental | Dose order: Arbaclofen 15mg, Placebo, Arbaclofen 30mg Receives: Drug: Arbaclofen_15; Drug: Arbaclofen_30; Drug: Placebo |
| Arbaclofen_15, Arbaclofen_30, Placebo | Experimental | Dose order: Arbaclofen 15mg, Arbaclofen 30mg, Placebo Receives: Drug: Arbaclofen_15; Drug: Arbaclofen_30; Drug: Placebo |
| Arbaclofen_30, Arbaclofen_15, Placebo | Experimental | Dose order: Arbaclofen 30mg, Arbaclofen 15mg, Placebo Receives: Drug: Arbaclofen_15; Drug: Arbaclofen_30; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Through study completion, an average of 2 years.
Secondary outcomes (2)
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.
Measured: Through study completion, an average of 2 years.
Brain oscillations under sensory stimulation
Brain oscillations and event-related potentials will be recorded during sensory stimulation using high density electroencephalography.
Measured: Through study completion, an average of 2 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2018
- Study start1 Feb 2018
- Primary completion12 Mar 2020
- Study completion12 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Autism Spectrum DisorderStudies of the same condition, open and under way.
- More trials run by King's College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- 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.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 87 participants (actual)
Sponsor and investigators
- Lead sponsor
- King's College London
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr Grainne McAlonan, King's College London
- Investigators
- Grainne McAlonan, PhD, Principal investigator, King's College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03594552
- Sponsor's protocol ID
- HR16-17 4081
- Status last verified
- Nov 2022
- First submitted
- 27 Jun 2018
- Last updated
- 22 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Modulation of the Brain Excitatory/Inhibitory (E/I) Balance Through Neuronal and Glial Systems in Autism Spectrum Disorder (ASD
- ClinicalTrials.gov ID
- NCT03594552
- Acronym / sponsor ID
- HR16-17 4081
- Conditions
- Autism Spectrum Disorder
- Keywords
- Autism Spectrum Disorder, Arbaclofen, E-I balance, pharmacological imaging, GABA
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 87 participants (actual)
- Lead sponsor
- King's College LondonUniversity, hospital or other
- Study start
- 1 Feb 2018 (actual)
- Primary completion
- 12 Mar 2020 (actual)
- Study completion
- 12 Mar 2020 (actual)
- First posted
- 20 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 6
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Placebo, Arbaclofen_15, Arbaclofen_30 | Experimental | Drug: Arbaclofen_15, Drug: Arbaclofen_30, Drug: PlaceboDose order: Placebo, Arbaclofen 15mg, Arbaclofen 30mg |
| Placebo, Arbaclofen_30, Arbaclofen_15 | Experimental | Drug: Arbaclofen_15, Drug: Arbaclofen_30, Drug: PlaceboDose order: Placebo, Arbaclofen 30mg, Arbaclofen 15 mg |
| Arbaclofen_30, Placebo, Arbaclofen_15 | Experimental | Drug: Arbaclofen_15, Drug: Arbaclofen_30, Drug: PlaceboDose order: Arbaclofen 30mg, Placebo, Arbaclofen 15mg |
| Arbaclofen_15, Placebo, Arbaclofen_30 | Experimental | Drug: Arbaclofen_15, Drug: Arbaclofen_30, Drug: PlaceboDose order: Arbaclofen 15mg, Placebo, Arbaclofen 30mg |
| Arbaclofen_15, Arbaclofen_30, Placebo | Experimental | Drug: Arbaclofen_15, Drug: Arbaclofen_30, Drug: PlaceboDose order: Arbaclofen 15mg, Arbaclofen 30mg, Placebo |
| Arbaclofen_30, Arbaclofen_15, Placebo | Experimental | Drug: Arbaclofen_15, Drug: Arbaclofen_30, Drug: PlaceboDose order: Arbaclofen 30mg, Arbaclofen 15mg, Placebo |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Arbaclofen_15Also: r-baclofen, STX209Single oral dose (15mg) | Drug | 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_30Also: r-baclofen, STX209Single oral dose (30mg) | Drug | 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 |
| PlaceboAlso: Placebo oral tabletSingle oral dose placebo (oral tablet) | Drug | 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 |
Primary outcome
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.
2 secondary outcomes
Functional connectivity measures using resting state functional magnetic resonance imaging.
Time frame: Through study completion, an average of 2 years.
Brain oscillations under sensory stimulation
Time frame: Through study completion, an average of 2 years.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Grainne McAlonan, PhD principal investigator
King's College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Arbaclofen_15 and Arbaclofen_30 in people with Autism Spectrum Disorder, run by King's College London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Neurochemical response to GABAergic stimulation. (time frame: Through study completion, an average of 2 years.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2022.