Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability

Intellectual Disability Clinical Trial

Official title:

A Randomized Placebo-controlled Trial of Cannabidiol to Treat Severe Behavioral Problems in Children and Adolescents With Intellectual Disability

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04821856
• Other study ID #: RCH HREC 70053
• Status: Recruiting
• Phase: Phase 2
• Start date: May 11, 2021
• Est. completion date: July 2024

Study information

• Verified date: August 2023
• Source: Murdoch Childrens Research Institute
• Contact: Daryl Efron
• Phone: +61 (3) 8341 6200
• Email: mctrials[@]mcri.edu.au
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 140
• Est. completion date: July 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 18 Years

Eligibility

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.

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

Related Conditions & MeSH terms

• Child Behavior Problem
• Intellectual Disability
• Problem Behavior

Intervention

Drug:
• Cannabidiol Oil
Cannabidiol (CBD) isolate 100mg/ml in MCT oil oral solution, manufactured by THC Pharma
• Placebo
MCT oil and flavoring solution, also manufactured by THC Pharma

Locations

Country	Name	City	State
Australia	Monash Children's Hospital	Clayton	Victoria
Australia	Royal Children's Hospital / Murdoch Children's Research Institute	Parkville	Victoria
Australia	The Children's Hospital at Westmead	Westmead	New South Wales

Sponsors (4)

Lead Sponsor	Collaborator
Murdoch Childrens Research Institute	Deakin University, Monash University, University of Sydney

Country where clinical trial is conducted

Australia, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Comparing the health sector cost-effectiveness of cannabidiol vs placebo in terms of Aberrant Behavior Checklist - Irritability (ABC-I) scores at day 64	This involves calculation of an incremental cost effectiveness ratio (ICER): health sector costs (CBD-placebo) divided by incremental ABC-I scores. Health sector costs will be calculated through: (1) Estimation of intervention costs from the study's financial records; (2) A brief Resource Use Questionnaire, completed by parents at day 64, which will capture medication and health sector resource use associated with their child's behaviour across the 8 week intervention period.	At day 64 (end of maintenance treatment period)
Other	Comparing the societal cost-effectiveness of cannabidiol vs placebo in terms of Aberrant Behavior Checklist - Irritability (ABC-I) scores at day 64	This involves calculation of an incremental cost effectiveness ratio (ICER): societal costs (CBD-placebo) divided by incremental ABC-I scores. Societal costs will be calculated through a brief Resource Use Questionnaire, completed by parents at day 64, which will capture societal resource use and lost productivity associated with their child's behaviour across the 8 week intervention period.	At day 64 (end of maintenance treatment period)
Other	Comparing the health sector cost-effectiveness of cannabidiol vs placebo in terms of Quality Adjusted Life Years calculated from the CHU-9D at day 64	This involves calculation of an incremental cost effectiveness ratio (ICER): health sector costs (CBD-placebo) divided by incremental Quality adjusted life years (QALYs) from CHU-9D . Health sector costs will be calculated through: (1) Estimation of intervention costs from the study's financial records; (2) A brief Resource Use Questionnaire, completed by parents at day 64, which will capture medication and health sector resource use associated with their child's behaviour across the 8 week intervention period.	At day 64 (end of maintenance treatment period)
Other	Comparing the societal cost-effectiveness of cannabidiol vs placebo in terms of Quality Adjusted Life Years calculated from the CHU-9D at day 64	This involves calculation of an incremental cost effectiveness ratio (ICER): societal costs (CBD-placebo) divided by incremental Quality adjusted life years (QALYs) from CHU-9D . Societal costs will be calculated through a brief Resource Use Questionnaire, completed by parents at day 64, which will capture societal resource use and lost productivity associated with their child's behaviour across the 8 week intervention period.	At day 64 (end of maintenance treatment period)
Other	Comparing the health sector cost-effectiveness of cannabidiol vs placebo in terms of Quality Adjusted Life Years calculated from the AQOL-4D at day 64	This involves calculation of an incremental cost effectiveness ratio (ICER): health sector costs (CBD-placebo) divided by incremental Quality adjusted life years (QALYs) from AQOL-4D . Health sector costs will be calculated through: (1) Estimation of intervention costs from the study's financial records; (2) A brief Resource Use Questionnaire, completed by parents at day 64, which will capture medication and health sector resource use associated with their child's behaviour across the 8 week intervention period.	At day 64 (end of maintenance treatment period)
Other	Comparing the societal cost-effectiveness of cannabidiol vs placebo in terms of Quality Adjusted Life Years calculated from the AQOL-4D at day 64	This involves calculation of an incremental cost effectiveness ratio (ICER): societal costs (CBD-placebo) divided by incremental Quality adjusted life years (QALYs) from AQOL-4D . Societal costs will be calculated through a brief Resource Use Questionnaire, completed by parents at day 64, which will capture societal resource use and lost productivity associated with their child's behaviour across the 8 week intervention period.	At day 64 (end of maintenance treatment period)
Primary	Mean difference between the cannabidiol 100mg/ml and placebo arms on the Aberrant Behavior Checklist-Irritability (ABC-I) subscale total score at day 64	This is a 15 item parent-rated questionnaire, used to measure Severe Behavioral Problems in children	At day 64 (end of maintenance treatment period)
Secondary	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	43 parent-rated items assessing: Social withdrawal, Stereotypic behavior, Hyperactivity/Noncompliance and Inappropriate Speech	At day 64 (end of maintenance treatment period)
Secondary	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	This is a single item clinician-rated summary measure of improvement	At day 64 (end of maintenance treatment period)
Secondary	Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Parent Rated Anxiety Scale-ASD at day 64	This is a 25 item parent-rated measure of anxiety in youth with ASD	At day 64 (end of maintenance treatment period)
Secondary	Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Child & Adolescent Scale of Participation at day 64	This is a 20 item parent-rated questionnaire that includes sub-scales for participation in home, school, and community activities	At day 64 (end of maintenance treatment period)
Secondary	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	This is a 9 item parent-rated, preference-weighted measure used to calculate quality adjusted life years for children	At day 64 (end of maintenance treatment period)
Secondary	Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Sleep Disturbance Scale for Children at day 64	This is a 26 item parent-rated questionnaire assessing sleep difficulties in children	At day 64 (end of maintenance treatment period)
Secondary	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	This is a 12 item self-report health-related instrument used to calculate quality adjusted life years for parents	At day 64 (end of maintenance treatment period)
Secondary	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	This is a 25 item parent report measure that includes subscales assessing family interaction, parenting, emotional and material wellbeing, and disability-related support.	At day 64 (end of maintenance treatment period)
Secondary	Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Depression Anxiety Stress Scale-21 at day 64	This is a 21 item self-rated assessment of parent mental health, including symptoms of depression, anxiety and stress	At day 64 (end of maintenance treatment period)
Secondary	Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Autism Parenting Stress Index at day 64	This is a 13 item self-rated measure of 3 categories of stress drivers in parents: core social disability, difficult behavior, physical issues	At day 64 (end of maintenance treatment period)
Secondary	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	Completed by the parent or guardian, the LAEP was designed to capture known side-effects of anti-epileptic medication. The modified version includes additional items to ascertain other known side-effects of CBD. This measure includes 34 items.	At day 64 (end of maintenance treatment period)