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Trial registered on ANZCTR


Registration number
ACTRN12625001088437
Ethics application status
Approved
Date submitted
16/09/2025
Date registered
7/10/2025
Date last updated
7/10/2025
Date data sharing statement initially provided
7/10/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Cannabidiol (CBD) for Irritability and Aggression in Autism Spectrum Disorder (ASD): A Phase 2 Study
Scientific title
A Phase 2 Trial to Evaluate the Efficacy and Safety of Cannabidiol (CBD) in Reducing Irritability and Aggressive Behaviour in Autism Spectrum Disorder (ASD), with a 12-Week Open-Label Extension Phase.
Secondary ID [1] 315391 0
NEB-777-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Autism Spectrum Disorder 338895 0
Condition category
Condition code
Mental Health 335189 335189 0 0
Autistic spectrum disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The trial consists of two phases:
Randomized, Double-Blind, Placebo-Controlled Phase (Weeks 0–12) with 3 treatment arms:
Arm 1: CBD 20 mg/kg/day (10 mg/kg taken orally twice daily, BD)
Arm 2: CBD 10 mg/kg/day (5 mg/kg taken orally twice daily BD)
Arm 3: CBD 6 mg/kg/day (3 mg/kg taken orally twice daily BD)

Duration: 12 weeks

Open-Label Extension Phase (OLE; Weeks 12–24):
All participants who complete the 12-week randomized phase are intended to proceed into the 12-week Open-Label Extension (Phase 2); this is not a separate cohort. No wash-out period for CBD is required. However, if a participant was using melatonin and/or NAC (non-study) during Phase 1, they must stop these at least 2 weeks before OLE enrolment—i.e., a 2-week wash-out for those adjuncts only.
All participants receive CBD. Participants either continue CBD at their prior dose (if they were on CBD in Phase 1) or start CBD at OLE Day 1 if they were on placebo at 7.5 mg/kg taken orally twice daily.
Participants are randomized to two adjunct sequences:
Sequence A: CBD + NAC (Weeks 12–18), then CBD + NAC + Melatonin (Weeks 18–24)
Sequence B: CBD + Melatonin (Weeks 12–18), then CBD + Melatonin + NAC (Weeks 18–24)
Adjunctive Treatments (OLE Phase)
1. Melatonin
Dose: 2 mg nightly (more than 35 kg) or 4 mg nightly (less than or equal to 35 kg)
Route: Oral (capsule or solution, ARTG-registered products)
Timing: 30 min before bedtime; no food within 2 hours before administration

2. N-acetylcysteine (NAC)
Dose: 60–80 mg/kg/day in two divided doses (BD), max 2700 mg/day
Route: Oral (solution or effervescent tablets)
Duration: Introduced sequentially for 12 weeks for all participants, as per randomised sequence

Dosing is fixed, oral, weight-based, with no escalation; adherence monitored via pill counts, diaries, and optional plasma CBD levels.
Intervention code [1] 332002 0
Treatment: Drugs
Comparator / control treatment
The comparator is a matching placebo administered orally twice daily (BD) for 12 weeks during the randomized, double-blind phase. The placebo is identical in appearance, packaging, and labeling to the active cannabidiol (CBD) treatments to maintain blinding. It is taken with food at the same frequency and duration as the active arms.

No control arm for the open-label extension phase (Weeks 12–24).
Control group
Placebo

Outcomes
Primary outcome [1] 342805 0
Evaluate the effect of CBD (alone and with melatonin) in changing irritability and aggression in ASD. (composite outcome)
Timepoint [1] 342805 0
Baseline, Week 4, Week 8, Week 12, Week 18 (OLE), Week 24 (OLE) post-first dose.
Secondary outcome [1] 452191 0
Assess safety and tolerability of CBD (composite outcome)
Timepoint [1] 452191 0
Screening, Baseline, Week 4, Week 8, Week 12, Week 18 (OLE), Week 24 (OLE) post-first dose.
Secondary outcome [2] 452192 0
Evaluate changes in Sleep patterns - latency, duration, quality (composite outcome)
Timepoint [2] 452192 0
Baseline, Week 4, Week 8, Week 12, Week 18 (OLE), Week 24 (OLE) post-first dose
Secondary outcome [3] 452511 0
Evaluate changes in Anxiety and emotional regulation.
Timepoint [3] 452511 0
Baseline, Week 4, Week 8, Week 12, Week 18 (OLE), Week 24 (OLE) post-first dose
Secondary outcome [4] 452512 0
Evaluate changes in Caregiver burden and quality of life.
Timepoint [4] 452512 0
Baseline, Week 4, Week 8, Week 12, Week 18 (OLE), Week 24 (OLE) post-first dose
Secondary outcome [5] 452513 0
Evaluate changes in Aggressive behaviours.
Timepoint [5] 452513 0
Baseline, Week 4, Week 8, Week 12, Week 18 (OLE), Week 24 (OLE) post-first dose

Eligibility
Key inclusion criteria
1. Age: 5 to no older than 25 years.
2. ASD level 2 or level 3 (DSM-5 criteria), as diagnosed by a pediatrician or psychiatrist.
3. ABC-I subscale score more than or equal to 18 and CGI-S score more than or equal to 4.
4. Not currently receiving any oral or intramuscular anti-psychotic medications (typical or atypical).
5. Participants taking melatonin and/or NAC are eligible to participate in the first phase of the trial. However, to be eligible for the OLE phase, participants must cease taking melatonin and NAC at least two weeks prior to enrolment. Participants will still be eligible for the first phase of the study even if they choose not to cease taking melatonin and/or NAC.
6. Stable concomitant medications (more than or equal to 4 weeks) before enrolment, excluding anti-psychotics, which are not permitted at study entry..
7. Caregiver or participant ability to complete assessments.
8. Willingness to provide informed consent/assent, as appropriate, based on age and legal requirements.
9. Caregiver availability to assist with study requirements, including completing assessments.
10. Body mass index (BMI) within the 5th to 95th percentile for age and gender.
11. No significant abnormalities in screening laboratory values that would preclude participation.
12. No active infections at the time of screening or baseline.
13. Normal or corrected vision to complete required study assessments.
14. Capable of swallowing oral medications without difficulty.
15. Stable housing environment for the duration of the study.
16. Consistent sleep schedule with no significant disruptions during the screening period.
17. Agreement to avoid initiating new behavioural or pharmacological treatments during the study.
18. No prior participation in other interventional trials within the last 30 days.
19. Stable seizure control (if applicable) with no changes in antiepileptic medications in the past 6 months.
20. No history of substance abuse or dependence within the last year.
21. No clinically significant cardiac, renal, hepatic, or respiratory conditions.
22. Demonstrated capacity to adhere to the visit schedule and study requirements.
Minimum age
5 Years
Maximum age
25 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Current use of any anti-psychotic medication (oral or intramuscular, typical or atypical).
2. Severe psychiatric or neurological conditions unrelated to ASD.
3. Uncontrolled seizure disorder or recent antiepileptic medication changes.
4. Known hypersensitivity to CBD or melatonin. Participants with hypersensitivity to melatonin will be excluded from OLE but are eligible to be enrolled in the first phase of the study.
5. Concurrent enrollment in another interventional clinical trial.
6. Pregnant or breastfeeding individuals.
7. Known or suspected history of significant gastrointestinal disorders affecting drug absorption.
8. History of suicidal ideation or behaviour within the last 6 months.
9. Any active autoimmune disorders requiring systemic immunosuppressive therapy.
10. Positive screen for active drug or alcohol abuse.
11. Involvement in any legal or custodial disputes likely to interfere with participation.
12. Diagnosis of severe intellectual disability preventing meaningful participation in assessments.
13. History of severe adverse reactions to cannabinoids or related compounds.
14. Recent history (within 3 months) of major surgery or hospitalization.
15. Clinically significant abnormal findings on screening ECG.
16. Elevated liver transaminases (ALT or AST) exceeding 2.5 times the upper limit of normal.
17. Known active malignancy or history of cancer within the last 5 years (except for localized basal cell carcinoma).
18. Chronic or acute infectious diseases requiring ongoing treatment (e.g., tuberculosis, hepatitis B/C, HIV).
19. Inability to commit to study visits or comply with medication regimen.
20. Concurrent use of prohibited medications that could interact with study treatments.
21. Planned or foreseeable likelihood of initiation of other behaviour-modifying medication during the initial 12-week study phase.

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)
central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer-generated, stratified by age group (5 to less than 12 years, 12 to less than 18 years, 18 to no older than 25 years), block randomization within each stratum, independently prepared to minimize selection bias.
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
The people analysing the results/data
Intervention assignment
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
3/11/2025
Actual
Date of last participant enrolment
Anticipated
3/11/2027
Actual
Date of last data collection
Anticipated
31/05/2028
Actual
Sample size
Target
120
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Funding & Sponsors
Funding source category [1] 319983 0
Commercial sector/Industry
Name [1] 319983 0
NeuroElevate Biosciences
Country [1] 319983 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
NeuroElevate Biosciences
Address
Country
Australia
Secondary sponsor category [1] 322510 0
None
Name [1] 322510 0
Address [1] 322510 0
Country [1] 322510 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 318521 0
Bellberry Human Research Ethics Committee A
Ethics committee address [1] 318521 0
Ethics committee country [1] 318521 0
Australia
Date submitted for ethics approval [1] 318521 0
30/07/2025
Approval date [1] 318521 0
05/09/2025
Ethics approval number [1] 318521 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 144450 0
Dr Dima El-Sukkari
Address 144450 0
Vitalis Clinical Research, 456 St Kilda Rd, Melbourne VIC 3004
Country 144450 0
Australia
Phone 144450 0
+61 03 9041 7159
Fax 144450 0
Email 144450 0
[email protected]
Contact person for public queries
Name 144451 0
Darryl Davies
Address 144451 0
iNGENu CRO, Unit 22/456 St Kilda Rd, Melbourne VIC 3004
Country 144451 0
Australia
Phone 144451 0
+61 1300 030 380
Fax 144451 0
Email 144451 0
[email protected]
Contact person for scientific queries
Name 144452 0
Darryl Davies
Address 144452 0
iNGENu CRO, Unit 22/456 St Kilda Rd, Melbourne VIC 3004
Country 144452 0
Australia
Phone 144452 0
+61 1300 030 380
Fax 144452 0
Email 144452 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


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.