GABA Pathways in Autism Spectrum Disorder (ASD)

NCT03678129 | Completed

• 1 other identifier: REC 18/WM/0208
• Study Type: interventional
• Target: 109
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Autism Spectrum Disorder

Keywords

Autism Spectrum Disorder; E-I balance; AZD7325; pharmacological imaging; GABA

Outcome Measures

Primary Outcomes (3)

• Brain activation and connectivity response to GABAergic stimulation as assessed by functional magnetic resonance imaging.

  Comparing whole brain blood-oxygen-level-dependent (BOLD) activation (institutional units) during the resting state in cases and controls when a single oral dose of GABA-A receptor acting compound administered versus the placebo condition.

  Data collected on up to 3 visit days per participant. Completed within up to 1 year.

• Brain electrophysiological activity task-free electroencephalography (EEG)

  Case-control comparison of task-free Electroencephalogram (EEG) during placebo and when GABA-A compound administered. Analyses approaches will include examining power and phase information across different frequencies and aperiodic signal analysis (1/f like); and evaluation of power spectrum and functional connectivity across source localisations.

  Data collected on up to 3 visit days per participant. Completed within up to 1 year

• Brain oscillations under sensory stimulation

  Brain oscillations (spectral perturbations) and event-related potentials will be recorded during sensory stimulation - auditory (odd-ball) and visual (contrast saturation, face perception/N170) tasks using electroencephalography during placebo and when GABA-A compound administered.

  Data collected on up to 3 visit days per participant. Completed within up to 1 year

Other Outcomes (3)

• Brain excitation and inhibition response to GABAergic stimulation as assessed by magnetic resonance spectroscopy.

  Data collected on up to 3 visit days per participant. Completed within up to 1 year

• Tactile perception

  Data collected on up to 3 visit days per participant. Completed within up to 1 year

• Electroretinogram

  Data collected on up to 3 visit days per participant. Completed within up to 1 year

Study Arms (2)

AZD7325

OTHER

Prepandemic. Single Dose of Placebo or AZD7325 10mg or AZD7325 20mg random order on visits separated by 1 week

Drug: AZD7325_10; Drug: AZD7325_20; Drug: Placebo

Clobazam

OTHER

Post pandemic: Single Dose Placebo or 5mg Clobazam random order on visits separated by 1 week

Drug: Placebo; Drug: Clobazam

Interventions

AZD7325_10 DRUG

Single oral dose (10mg)

AZD7325

AZD7325_20 DRUG

Single oral dose (20mg)

AZD7325

Placebo DRUG

Single oral dose placebo (capsule)

AZD7325; Clobazam

Clobazam DRUG

Single dose (5mg)

Clobazam

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• For all participants:
• Calendar age above 18 years.
• Able to give informed consent.
• Not pregnant or breastfeeding.
• Ideally prescription medication free during the 2-week period preceding a study visit. However, occasional use of over-the-counter medication (e.g. painkillers) on an as needed basis (and not on the day of study visit) may be permitted. In addition, regular prescription medication (use of a stable dose over the two months preceding participation) with a drug that does not affect glutamate or GABA directly may be permitted. Also permitted is topical medication without systemic exposure.
• For individuals with ASD:
• \. Diagnosis of ASD confirmed on the Autism Diagnostic Interview-Revised (ADI-R) if a relative is available and/or on the Autism Diagnostic Observation Schedule (ADOS-2).
• For all relatives:
• Aged under 18 years.
• Does not know the participant personally at present or in their childhood.

You may not qualify if:

• For all participants
• History of allergy/idiosyncrasy to AZD7325 or chemically related compounds or excipients which may be employed in the study or to any other drug used in the past.
• Subject has taken systemically (po, iv) any potent or moderate CYP3A4 or CYP2C9 inhibitor or inducer, 1 month prior to screening (topical or inhaled are permitted) such as: aprepitant, barbiturates, carbamazepine, clarithromycin, erythromycin, cyclosporine, diltiazem, efavirenz, fluconazole, HIV protease inhibitors, glucocorticoids, itraconazole (oral/IV), ketoconazole, nefazodone, nevirapine, phenytoin, pioglitazone, primidone, rifabutin, rifampicin, telithromycin, St. John's wort, verapamil.
• Clinically relevant history or presence of any medical disorder, potentially interfering with this study.
• Clinically relevant abnormality at screening as judged by the investigator.
• History of or current abuse of drugs (including prescription medication) or alcohol or solvents.
• Participation in a research study involving a pharmacological probe or drug trial within last month or more than four in the previous 12 months
• Subjects with a history of epilepsy, seizures or episodes of unexplained and unprovoked loss of consciousness.
• Anyone with a history or examination which indicates laboratory testing is needed will be excluded from the study.
• Intelligence Quotient below 70.
• Reproductive safety: Male study participants who are sexually active should avoid procreation for 1 week after study drug administration. Avoidance of procreation can be through use of a highly effective contraception method by the study participant or by the partner. In this case, effective means of contraception are defined as tubal occlusion, copper banded intrauterine device, levonorgestrel medicated intra uterine system (e.g., Mirena), medroxyprogesterone injections (e.g. Depo-Provera), etonogestrel implants (e.g., Implanon, Norplan), normal and low dose combined oral contraceptive pills, norelgestromin / EE transdermal system, intravaginal device (e.g., EE and etonogestrel) and desogestrel (Cerazette).
• For individuals with ASD:
• ASD caused by a known genetic syndrome, e.g. Fragile X, 22q11 deletion syndrome.
• Currently treated for epilepsy.

Sponsors & Collaborators

• King's College London: lead

Study Sites (1)

King's College London

London, London, SE5 8AF, United Kingdom

Location

MeSH Terms

Conditions

Autism Spectrum Disorder

Interventions

Clobazam

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Grainne McAlonan, PhD

  King's College London, UK

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Participants and investigators are blinded to the drug condition
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Case-control comparison. Repeated-measures cross-over design. Prepandemic, each subject received each one of the three pharmacological probes in separate visits (i.e., placebo, AZD7325 low dose and AZD7325 high dose), with the order of capsule administration being pseudorandomized. Post pandemic, each participant receives either placebo or 5mg clobazam with the order pseudorandomized.

Study Record Dates

• First Submitted: September 18, 2018
• First Posted: September 19, 2018
• Study Start: December 7, 2018
• Primary Completion: June 27, 2025
• Study Completion: June 27, 2025
• Last Updated: August 26, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)