Autism Spectrum DisorderNCT03678129
GABA Pathways in Autism Spectrum Disorder (ASD)
A study testing AZD7325_10, AZD7325_20 and Clobazam 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 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. 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?
- AZD7325_10, AZD7325_20 and Clobazam
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 109 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 7 Dec 2018to 27 Jun 2025
- 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
- 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:
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- 1. 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.
Who cannot join
- 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.
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- 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).
- Pregnancy or breastfeeding (is a routine exclusion for research MRI scanning). Female study participants must be willing to use one form of highly effective non-hormonal contraception for one week after study drug administration. This would include a vasectomised partner (sole partner), tubal occlusion, intrauterine system [IUS]/hormonal coil or copper containing intrauterine device or copper containing IUD, or true abstinence (when this is in line with the preferred and usual lifestyle of the subject). Women should have been stable on their chosen method of birth control for a minimum of 2 months before entering the study. Participants must agree to undergo a pregnancy test prior to each administration of study drug.
- For individuals with ASD:
- ASD caused by a known genetic syndrome, e.g. Fragile X, 22q11 deletion syndrome.
- Currently treated for epilepsy.
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 Systems in Autism Spectrum Disorder (ASD)
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.
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 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
- Being tested
- AZD7325_10, AZD7325_20, Placebo, Clobazam
- Keywords
- Autism Spectrum Disorder, E-I balance, AZD7325, 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.
AZD7325_10Drug
Single oral dose (10mg)
AZD7325_20Drug
Single oral dose (20mg)
PlaceboDrug
Single oral dose placebo (capsule)
ClobazamDrug
Single dose (5mg)
| Study group | Role | What they receive |
|---|---|---|
| AZD7325 | Other | Prepandemic. Single Dose of Placebo or AZD7325 10mg or AZD7325 20mg random order on visits separated by 1 week Receives: 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 Receives: Drug: Placebo; Drug: Clobazam |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Data collected on up to 3 visit days per participant. Completed within up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2018
- Study start7 Dec 2018
- Primary completion27 Jun 2025
- Study completion27 Jun 2025
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.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 109 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, UK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03678129
- Sponsor's protocol ID
- REC 18/WM/0208
- Status last verified
- Aug 2025
- First submitted
- 18 Sep 2018
- Last updated
- 26 Aug 2025
- 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 26 Aug 2025. 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 Systems in Autism Spectrum Disorder (ASD)
- ClinicalTrials.gov ID
- NCT03678129
- Acronym / sponsor ID
- REC 18/WM/0208
- Conditions
- Autism Spectrum Disorder
- Keywords
- Autism Spectrum Disorder, E-I balance, AZD7325, pharmacological imaging, GABA
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 109 participants (actual)
- Lead sponsor
- King's College LondonUniversity, hospital or other
- Study start
- 7 Dec 2018 (actual)
- Primary completion
- 27 Jun 2025 (actual)
- Study completion
- 27 Jun 2025 (actual)
- First posted
- 19 Sep 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 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
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| AZD7325 | Other | Drug: AZD7325_10, Drug: AZD7325_20, Drug: PlaceboPrepandemic. Single Dose of Placebo or AZD7325 10mg or AZD7325 20mg random order on visits separated by 1 week |
| Clobazam | Other | Drug: Placebo, Drug: ClobazamPost pandemic: Single Dose Placebo or 5mg Clobazam random order on visits separated by 1 week |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- 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.
- 1. 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).
Key exclusion criteria (15 listed)
- 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.
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 |
|---|---|---|
| AZD7325_10Single oral dose (10mg) | Drug | AZD7325 |
| AZD7325_20Single oral dose (20mg) | Drug | AZD7325 |
| PlaceboSingle oral dose placebo (capsule) | Drug | AZD7325, Clobazam |
| ClobazamSingle dose (5mg) | Drug | Clobazam |
Primary outcome
Brain activation and connectivity response to GABAergic stimulation as assessed by functional magnetic resonance imaging.
Time frame: Data collected on up to 3 visit days per participant. Completed within up to 1 year.
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.
Brain electrophysiological activity task-free electroencephalography (EEG)
Time frame: Data collected on up to 3 visit days per participant. Completed within up to 1 year
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.
Brain oscillations under sensory stimulation
Time frame: Data collected on up to 3 visit days per participant. Completed within up to 1 year
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.
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 26 Aug 2025.
- 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, UK
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing AZD7325_10, AZD7325_20 and Clobazam 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 10 inclusion and 15 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 26 Aug 2025. 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?
Brain activation and connectivity response to GABAergic stimulation as assessed by functional magnetic resonance imaging. (time frame: Data collected on up to 3 visit days per participant. Completed within up to 1 year.). The study lists 3 primary outcomes in all. 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 26 Aug 2025.