Clinical trial NCT04821856: Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
Official title: A Randomized Placebo-controlled Trial of Cannabidiol to Treat Severe Behavioral Problems in Children and Adolescents With Intellectual Disability
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Intellectual Disability
Child Behavior Problem
Keywords: pediatric
intellectual disability
severe behavior problems
Lead sponsor: Murdoch Childrens Research Institute
Sponsor class: OTHER
Collaborators: name: Monash University
name: University of Sydney
name: Deakin University
First posted: 2021-03-30
Enrollment: 140
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Mean difference between the cannabidiol 100mg/ml and placebo arms on the Aberrant Behavior Checklist-Irritability (ABC-I) subscale total score at day 64
timeFrame: At day 64 (end of maintenance treatment period)
Secondary outcomes:
measure: 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
timeFrame: At day 64 (end of maintenance treatment period)
measure: 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
timeFrame: At day 64 (end of maintenance treatment period)
measure: Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Parent Rated Anxiety Scale-ASD at day 64
timeFrame: At day 64 (end of maintenance treatment period)
measure: Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Child & Adolescent Scale of Participation at day 64
timeFrame: At day 64 (end of maintenance treatment period)
measure: 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
timeFrame: At day 64 (end of maintenance treatment period)
measure: Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Sleep Disturbance Scale for Children at day 64
timeFrame: At day 64 (end of maintenance treatment period)
measure: 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
timeFrame: At day 64 (end of maintenance treatment period)
measure: 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
timeFrame: At day 64 (end of maintenance treatment period)
measure: Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Depression Anxiety Stress Scale-21 at day 64
timeFrame: At day 64 (end of maintenance treatment period)
measure: Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Autism Parenting Stress Index at day 64
timeFrame: At day 64 (end of maintenance treatment period)
measure: 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
timeFrame: At day 64 (end of maintenance treatment period)
Other outcomes:
measure: Comparing the health sector cost-effectiveness of cannabidiol vs placebo in terms of Aberrant Behavior Checklist - Irritability (ABC-I) scores at day 64
timeFrame: At day 64 (end of maintenance treatment period)
measure: Comparing the societal cost-effectiveness of cannabidiol vs placebo in terms of Aberrant Behavior Checklist - Irritability (ABC-I) scores at day 64
timeFrame: At day 64 (end of maintenance treatment period)
measure: 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
timeFrame: At day 64 (end of maintenance treatment period)
measure: Comparing the societal cost-effectiveness of cannabidiol vs placebo in terms of Quality Adjusted Life Years calculated from the CHU-9D at day 64
timeFrame: At day 64 (end of maintenance treatment period)
measure: 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
timeFrame: At day 64 (end of maintenance treatment period)
measure: Comparing the societal cost-effectiveness of cannabidiol vs placebo in terms of Quality Adjusted Life Years calculated from the AQOL-4D at day 64
timeFrame: At day 64 (end of maintenance treatment period)
Locations:
city: Westmead
country: Australia
facility: The Children's Hospital at Westmead
state: New South Wales
city: Clayton
country: Australia
facility: Monash Children's Hospital
state: Victoria
city: Parkville
country: Australia
facility: Royal Children's Hospital / Murdoch Children's Research Institute
state: Victoria
Study officials:
affiliation: Murdoch Childrens Research Institute
name: Daryl Efron
role: STUDY_DIRECTOR
References:
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.
citation: 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.