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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04821856




Registration number
NCT04821856
Ethics application status
Date submitted
25/03/2021
Date registered
30/03/2021
Date last updated
3/08/2023

Titles & IDs
Public title
Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
Scientific title
A Randomized Placebo-controlled Trial of Cannabidiol to Treat Severe Behavioral Problems in Children and Adolescents With Intellectual Disability
Secondary ID [1] 0 0
RCH HREC 70053
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Intellectual Disability 0 0
Child Behavior Problem 0 0
Condition category
Condition code
Mental Health 0 0 0 0
Learning disabilities
Mental Health 0 0 0 0
Other mental health disorders
Mental Health 0 0 0 0
Studies of normal psychology, cognitive function and behaviour

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cannabidiol Oil
Treatment: Drugs - Placebo

Experimental: Cannabidiol 100mg/ml - The starting dose of cannabidiol (CBD) will be 5 mg/kg/day and will be administered orally twice daily in doses of 2.5 mg/kg (up titration phase from day 1 to 7). After one week, the dose of CBD will be increased to 10 mg/kg/day in two daily doses of 5mg/kg (8-week maintenance phase from day 8 to 63). On completion of the maintenance phase the dose of CBD will be decreased to 5mg/kg/day for one week (day 64 to 70), after which the CBD administration will cease.
A ceiling dose of 1000mg/day will be administered to all participants weighing 100kg or greater. These participants will receive a dose of 500mg/day during up- and down-titration.
Doses will be rounded to the nearest 10mg (0.1mL).

Placebo Comparator: Placebo - The control group will receive placebo medium-chain triglyceride (MCT) oil which is indistinguishable from the active medication in appearance, smell and taste.
Dose will be matched for volume to the cannabidiol arm, and administered twice daily for 10 weeks (including up- and down-titration).


Treatment: Drugs: Cannabidiol Oil
Cannabidiol (CBD) isolate 100mg/ml in MCT oil oral solution, manufactured by THC Pharma

Treatment: Drugs: Placebo
MCT oil and flavoring solution, also manufactured by THC Pharma
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Mean difference between the cannabidiol 100mg/ml and placebo arms on the Aberrant Behavior Checklist-Irritability (ABC-I) subscale total score at day 64
Timepoint [1] 0 0
At day 64 (end of maintenance treatment period)
Secondary outcome [1] 0 0
Mean difference between the cannabidiol 100mg/ml and placebo arms on the total scores of the four remaining subscales of the Aberrant Behavior Checklist (ABC) at day 64
Timepoint [1] 0 0
At day 64 (end of maintenance treatment period)
Secondary outcome [2] 0 0
Comparison between the cannabidiol 100mg/ml and placebo arms of clinician ratings on the Clinical Global Impressions-Improvement at day 64. Data will be presented as the proportion of participants in each arm with a rating suggesting improvement
Timepoint [2] 0 0
At day 64 (end of maintenance treatment period)
Secondary outcome [3] 0 0
Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Parent Rated Anxiety Scale-ASD at day 64
Timepoint [3] 0 0
At day 64 (end of maintenance treatment period)
Secondary outcome [4] 0 0
Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Child & Adolescent Scale of Participation at day 64
Timepoint [4] 0 0
At day 64 (end of maintenance treatment period)
Secondary outcome [5] 0 0
Mean difference between the cannabidiol 100mg/ml and placebo arms on the weighted total score of the Child Health Utility 9D (CHU-9D) at day 64
Timepoint [5] 0 0
At day 64 (end of maintenance treatment period)
Secondary outcome [6] 0 0
Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Sleep Disturbance Scale for Children at day 64
Timepoint [6] 0 0
At day 64 (end of maintenance treatment period)
Secondary outcome [7] 0 0
Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Assessment of Quality of Life 4D (AQOL-4D) at day 64
Timepoint [7] 0 0
At day 64 (end of maintenance treatment period)
Secondary outcome [8] 0 0
Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Beach Center Family Quality of Life at day 64
Timepoint [8] 0 0
At day 64 (end of maintenance treatment period)
Secondary outcome [9] 0 0
Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Depression Anxiety Stress Scale-21 at day 64
Timepoint [9] 0 0
At day 64 (end of maintenance treatment period)
Secondary outcome [10] 0 0
Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Autism Parenting Stress Index at day 64
Timepoint [10] 0 0
At day 64 (end of maintenance treatment period)
Secondary outcome [11] 0 0
The frequency of adverse events as reported on the modified version of the Liverpool Adverse Event Profile (LAEP) at day 64 will be summarised across the cannabidiol 100mg/ml and placebo arms
Timepoint [11] 0 0
At day 64 (end of maintenance treatment period)

Eligibility
Key inclusion criteria
1. Males and females aged 6 - 18 years of age;

2. DSM-5 diagnosis of intellectual disability (ID):

1. Full scale IQ < 70 on standardized cognitive assessment. Testing results must be
sighted by the investigators and performed within two years of enrollment. In the
event that records of prior testing are unavailable or the assessment was more
than 2 years prior, IQ will be estimated using the Wechsler Abbreviated Scale of
Intelligence-II.

2. Deficit in adaptive function (basis for severity rating of ID in DSM-5) in at
least one activity of life on the Vineland Adaptive Behavior Scales (derives
scores in Communication, Daily Living Skills and Socialization domains, and a
Global Adaptive score). If records of prior testing are unavailable or the
assessment was more than 2 years prior, this will be completed by the parent or
guardian.

3. SBP: Defined as scores of:

1. 18 or higher on the Aberrant Behavior Checklist-Irritability subscale (ABC-I),
and

2. moderate or higher on the Clinical Global Impressions-Severity scale;

4. No changes in either medication or other interventions in the 4 weeks prior to
randomization, and intention to remain on same dose for the duration of the study;

5. Written informed consent from parent or legal guardian;

6. Participant and family have the ability to comply with the protocol requirements, in
the opinion of the investigator.
Minimum age
6 Years
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Non-English speaking parents;

2. Psychosis;

3. Taking clobazam, mTOR inhibitors (e.g sirolimus, tacrolimus), anti-cancer agents,
citalopram >20mg/day, escitalopram >10mg/day.;

4. Abnormal liver function tests: defined as ALT > twice ULN;

5. Abnormal renal function tests: defined as creatinine > ULN

6. Current use of medicinal cannabis, or use in the 4 weeks prior to screening;

7. Pregnant or intending to become pregnant during the study, or breastfeeding;

8. Known allergy to cannabidiol or cannabis products

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
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/05/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/07/2024
Actual
Sample size
Target
140
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [2] 0 0
Monash Children's Hospital - Clayton
Recruitment hospital [3] 0 0
Royal Children's Hospital / Murdoch Children's Research Institute - Parkville
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
3052 - Parkville

Funding & Sponsors
Primary sponsor type
Other
Name
Murdoch Childrens Research Institute
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Monash University
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
University of Sydney
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Deakin University
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This is a multi-site, double-blind, parallel group, randomized, placebo-controlled study of
140 participants comparing oral purified cannabidiol isolate (CBD) with placebo in reducing
Severe Behavioral Problems (SBP) at 8 weeks in children aged 6 - 18 years with Intellectual
Disability (ID). Eligible participants will be randomized 1:1 to receive either CBD or
placebo.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04821856
Trial related presentations / publications
Efron D, Taylor K, Payne JM, Freeman JL, Cranswick N, Mulraney M, Prakash C, Lee KJ, Williams K. Does cannabidiol reduce severe behavioural problems in children with intellectual disability? Study protocol for a pilot single-site phase I/II randomised placebo controlled trial. BMJ Open. 2020 Mar 8;10(3):e034362. doi: 10.1136/bmjopen-2019-034362.
Efron D, Freeman JL, Cranswick N, Payne JM, Mulraney M, Prakash C, Lee KJ, Taylor K, Williams K. A pilot randomised placebo-controlled trial of cannabidiol to reduce severe behavioural problems in children and adolescents with intellectual disability. Br J Clin Pharmacol. 2021 Feb;87(2):436-446. doi: 10.1111/bcp.14399. Epub 2020 Jul 1.
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Daryl Efron
Address 0 0
Country 0 0
Phone 0 0
+61 (3) 8341 6200
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04821856