NCT03678129

GABA Pathways in Autism Spectrum Disorder (ASD)

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

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 109 (actual)
• Sponsor: King's College London · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Accepted

Summary

This study investigates the brain response to a single acute dose of a GABAa receptor acting drug (Benzodiazepine or positive allosteric modulator) compared to a single dose of placebo in adults 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 a GABA-A acting drug. Please note, when first registered we had access to the specific GABA-A (AZD7325) receptor positive allosteric modulator. Following a pause in the study over the Covid pandemic this compound was not longer available. Therefore, we have updated the protocol and instead are using clobazam, a GABA-A/benzodiazepine receptor agonist. We have also now expanded the information about measures acquired in this study. Up to 50 adult individuals with ASD and 50 neurotypical adults (25 males and 25 females per group) will be invited to participate. Prior to the pandemic, each participant received a single dose of the drug (10mg or 20mg AZD7325) or matched placebo. Following ethics amendment post pandemic, AZD7325 will no longer be used and participants will receive 5mg of clobazam or placebo. Brain activity and neurochemistry will be investigated using magnetic resonance imaging, EEG and psychophysics. Further data will be collected through questionnaires, behavioural tasks, blood samples, and retinal physiology. Our study is defined as a Basic Science study in human participants. It does not address safety or clinical efficacy and the UK Medicines and Health Regulatory Authority (MHRA) has confirmed that our protocol is therefore not a clinical trial of an Investigational Medicinal Product (IMP) as defined by the EU Directive 2001/20/EC

Conditions

• Autism Spectrum Disorder

Interventions

Type	Name	Description
DRUG	AZD7325_10	Single oral dose (10mg)
DRUG	AZD7325_20	Single oral dose (20mg)
DRUG	Placebo	Single oral dose placebo (capsule)
DRUG	Clobazam	Single dose (5mg)

Timeline

• Start date: 2018-12-07
• Primary completion: 2025-06-27
• Completion: 2025-06-27
• First posted: 2018-09-19
• Last updated: 2025-08-26

Locations

1 site across 1 country: United Kingdom