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Trial registered on ANZCTR


Registration number
ACTRN12622000437763
Ethics application status
Approved
Date submitted
28/02/2022
Date registered
18/03/2022
Date last updated
20/07/2023
Date data sharing statement initially provided
18/03/2022
Date results information initially provided
20/07/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Effects of cannabidiol in children with autism
Scientific title
A randomised crossover trial examining behavioural and neurophysiological effects of cannabidiol (CBD) in children with autism
Secondary ID [1] 306172 0
None
Universal Trial Number (UTN)
Trial acronym
CBDCA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Autism Spectrum Disorder 324880 0
Condition category
Condition code
Mental Health 322317 322317 0 0
Autistic spectrum disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Weight-based dosing of 10 mg/kg/day of cannabidiol (Medigrowth CBD100) for 12 weeks (delivered sublingually via syringe dispenser).
Washout period: 8 weeks.
Intervention code [1] 322580 0
Treatment: Drugs
Comparator / control treatment
MCT (coconut) oil delivered sublingually from syringe dispenser
Control group
Placebo

Outcomes
Primary outcome [1] 330083 0
• Social Responsiveness Scale (SRS; Constantino & Gruber, 2005, SRS-2; 2012)
The SRS-2 is a reliable 65-item measure of symptom severity across five autism symptom domains: Social Awareness (8 items), Social Motivation (11 items), Social Cognition (12 items), Social Communication (22 items), and Repetitive Behaviours/Restricted Interests (12 items). Responses are measured on a 4-point scale from 1 (Not True) to 4 (Almost Always True).
Timepoint [1] 330083 0
Baseline, 12 weeks post-commencement of CBD or MCT treatment
Primary outcome [2] 330084 0
Neurophysiological measure, electroencephalography (EEG):
Event-related gamma power during social (Emotion processing) task processing.
Timepoint [2] 330084 0
Baseline, 12 weeks post-commencement of CBD or MCT treatment
Secondary outcome [1] 404831 0
• Repetitive Behavior Scale-Revised (RBS-R)
The RBS-R is a 44-item self-report questionnaire used to measure the breadth of repetitive behavior in children, adolescents, and adults with autism.
Timepoint [1] 404831 0
Baseline, 12 weeks post-commencement of CBD or MCT treatment
Secondary outcome [2] 404832 0
• Vineland Adaptive Behaviour Scale-3 (VABS-3)
The VABS is a semi-structured caregiver interview designed to assess functional skills in five domains, each with two to three subdomains. The domains are communication, daily living skills, socialization, motor skills, and maladaptive behaviour.
Timepoint [2] 404832 0
Baseline, 12 weeks post-commencement of CBD or MCT treatment
Secondary outcome [3] 404834 0
• Pediatric Quality of Life Inventory (PedsQL)
The Pediatric Quality of Life Inventory (PedsQL) is a 23-item generic health status instrument with parent and child forms that assesses five domains of health (physical functioning, emotional functioning, psychosocial functioning, social functioning, and school functioning) in children and adolescents ages 2 to 18.
Timepoint [3] 404834 0
Baseline, 12 weeks post-commencement of CBD or MCT treatment
Secondary outcome [4] 404835 0
• Behaviour Rating Inventory of Executive Function - Second Edition (BRIEF 2)
The BRIEF is an 86-item parent report measure that assesses executive functioning skills in children 5-18 years. It comprised of 8 subscales (inhibit, shift, emotional control, initiate, working memory, plan/organise, organisation of materials, and monitor).
Timepoint [4] 404835 0
Baseline, 12 weeks post-commencement of CBD or MCT treatment
Secondary outcome [5] 406406 0
• Personal Wellbeing Index School Children (PWI-3-self-report)
The PWI scale contains 7 items of satisfaction, each one corresponding to a quality of life domain as: standard of living, health, achieving in life, relationships, safety, community-connectedness, and future security.
Timepoint [5] 406406 0
Baseline, 12 weeks post-commencement of CBD or MCT treatment
Secondary outcome [6] 410273 0
•Developmental Behaviour Checklist-2 (DBC-2) (Einfeld & Tonge, 1992, 2002)
The Developmental Behaviour Checklist 2 (DBC2) can be completed by a parent to describe emotional and behavioural problems.
Timepoint [6] 410273 0
Baseline, 12 weeks post-commencement of CBD or MCT treatment
Secondary outcome [7] 410274 0
•Autism Parenting Stress Index (APSI) (Silva & Schalock, 2012)
The APSI was developed following interviews of parents of children with autism. The Items fall into three categories: the core social disability, difficult-to-manage behaviour, and physical issues.
Timepoint [7] 410274 0
Baseline, 12 weeks post-commencement of CBD or MCT treatment
Secondary outcome [8] 410275 0
•PROMIS EC Parent-Report – Anxiety (PROMIS Health Organization and Assessment Center, 2014)
This is an 8-item parent report scale that measures anxiety in paediatric populations.
Timepoint [8] 410275 0
Baseline, 12 weeks post-commencement of CBD or MCT treatment
Secondary outcome [9] 410276 0
•PROMIS EC Parent-Report – Sleep Health (PROMIS Health Organization and Assessment Center, 2014)
This is an 8-item parent report scale that measures sleep H=health in paediatric populations.
Timepoint [9] 410276 0
Baseline, 12 weeks post-commencement of CBD or MCT treatment
Secondary outcome [10] 410277 0
•PROMIS EC Parent-Report – Social Relationships (PROMIS Health Organization and Assessment Center, 2014)
This is a 6-item parent report scale that measures social relationships in paediatric populations.
Timepoint [10] 410277 0
Baseline, 12 weeks post-commencement of CBD or MCT treatment

Eligibility
Key inclusion criteria
1. Male or female children aged between and including 5 to 12.

2. Diagnosis of Autism Spectrum Disorder (ASD) confirmed by The Autism Diagnostic Observation Schedule 2nd edition (ADOS-2). Children with autism will be identified in accordance with the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V; APA, 2013) criteria.

3. Stable pharmacologic, educational, behavioural, and/or dietary interventions for 4 weeks prior to randomisation and for the duration of the study;

4. Presence of a parent/guardian who can provide consent for the participation of their child and complete assessments regarding the child's development and behaviour throughout the study;

5. Normal/corrected to normal hearing and vision.

6. IQ of 40 or higher.
Minimum age
5 Years
Maximum age
12 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Exposure to any investigational agent in the 30 days prior to randomization;

2. Prior chronic treatment with CBD, CBDV or an endocannabinoid treatment;

3. Diagnosis of a known genetic disorder (e.g., Prader-Willi Syndrome, Angelman Syndrome, Tuberous Sclerosis);

4. A known diagnosis of Rett Syndrome or Childhood Disintegrative Disorder, or marked sensory impairment such as deafness or blindness;

5. A primary psychiatric diagnosis other than ASD, including bipolar disorder, psychosis, schizophrenia, Post-Traumatic Stress Disorder (PTSD) or Major Depressive Disorder (MDD). These patients will be excluded due to potential confounding results;

6. A medical condition that severely impacts the participant’s ability to participate in the study, interferes with the conduct of the study, confounds interpretation of study results, or endangers the participant’s well-being;

7. Changes in allied health therapies, behavioural, or educational interventions within 4 weeks prior to randomisation other than those associated with school holidays;

8. Changes in medications or medication doses within four weeks of randomisation.

9. Contraindications to CBD100: hypersensitivity to cannabinoids, liver, kidney or cardiovascular disease, hypersensitivity to the excipient (MCT) or coconut allergy

10. Currently taking benzodiazepines, antiepileptic medications (e.g., sodium valproate, clobazam), and barbiturates.

11. IQ below 40 or severe intellectual disability.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Crossover
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
21/10/2022
Actual
21/10/2022
Date of last participant enrolment
Anticipated
30/03/2023
Actual
30/03/2023
Date of last data collection
Anticipated
30/12/2023
Actual
Sample size
Target
34
Accrual to date
Final
34
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 310516 0
University
Name [1] 310516 0
Deakin University
Country [1] 310516 0
Australia
Primary sponsor type
University
Name
Deakin University
Address
221 Burwood Hwy, Burwood VIC 3125
Country
Australia
Secondary sponsor category [1] 311689 0
None
Name [1] 311689 0
Address [1] 311689 0
Country [1] 311689 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310141 0
Deakin University Health Research Ethics Committee (DUHREC)
Ethics committee address [1] 310141 0
Human Research Ethics Office
Deakin University
221 Burwood Hwy
Burwood, VIC 3125
Ethics committee country [1] 310141 0
Australia
Date submitted for ethics approval [1] 310141 0
21/03/2022
Approval date [1] 310141 0
22/07/2022
Ethics approval number [1] 310141 0
2022-071

Summary
Brief summary
Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder with no validated biomedical treatments for the core social and behavioural symptoms. The current study is a randomised crossover trial to assess whether cannabidiol (CBD) can promote behavioural and neurophysiological improvements in 5- to 12-year-old children.

Several recent studies have investigated acute CBD administration on neurophysiological processes in the adult autistic brain (Pretzsch, Freyberg, Voinescu, et al., 2019a; Pretzsch, Voinescu, Lythgoe, et al., 2019a, 2019b; Pretzsch et al., 2021a). Others have documented behavioural outcomes following chronic (long-term) administration of the compound (Aran et al., 2019, 2021; Bar-Lev Schleider et al., 2019). To date, no investigation has explored effects of long-term CBD administration on glutamate and GABA concentrations alongside social communication outcomes. With a specific focus on the Research Domain Criteria (RDoC) ‘social processes’ domain (Cuthbert & Insel, 2013), which is heavily implicated in ASD, this study will utilise electroencephalography (EEG) to measure neurophysiological changes after chronic administration of CBD over a 12-week period. EEG will be used to acquire resting-state, social task-related processing, and mismatch negativity (MMN) data. MMN is a recognised measure of glutamatergic NMDA receptor function, and thus, neuronal excitation (Kompus et al., 2015).

The study is designed to address the following aims:

Behavioural: to measure the effect of CBD on the RDoC social processes domain in children with autism. More specifically, to observe a change in Social Responsiveness Scale (SRS) scores from baseline to Week 12.

Neurophysiological: to observe whether CBD ‘shifts’ cortical excitation/inhibition during a social task, measured using EEG.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 116622 0
Dr Talitha Ford
Address 116622 0
Cognitive Neuroscience Unit (CNU), School of Psychology, Deakin University
221 Burwood Hwy, Burwood VIC 3125
Country 116622 0
Australia
Phone 116622 0
+61 03 92468730
Fax 116622 0
Email 116622 0
talitha.ford@deakin.edu.au
Contact person for public queries
Name 116623 0
Ms Nina Parrella
Address 116623 0
Cognitive Neuroscience Unit (CNU), School of Psychology, Deakin University
221 Burwood Hwy, Burwood VIC 3125
Country 116623 0
Australia
Phone 116623 0
+61 03 92468730
Fax 116623 0
Email 116623 0
parrellan@deakin.edu.au
Contact person for scientific queries
Name 116624 0
Ms Nina Parrella
Address 116624 0
Cognitive Neuroscience Unit (CNU), School of Psychology, Deakin University
221 Burwood Hwy, Burwood VIC 3125
Country 116624 0
Australia
Phone 116624 0
+61 03 92468730
Fax 116624 0
Email 116624 0
parrellan@deakin.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified data only: participant IDs, raw scores from primary and secondary outcome measures.
When will data be available (start and end dates)?
Beginning 3 months and ending 5 years following main results publication.
Available to whom?
Publicly available
Available for what types of analyses?
Any purpose
How or where can data be obtained?
Open Science Framework

Access to the data via Open Science Framework may be requested by emailing the principal invistigator, Talitha Ford, talitha.ford@deakin.edu.au


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.