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

Study Overview
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Brief Summary
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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.

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

Conditions
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Intellectual Disability, Child Behavior Problem

Intervention / Treatment
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* Drug: Cannabidiol Oil
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females aged 6 - 18 years of age; DSM-5 diagnosis of intellectual disability (ID): 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. 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. SBP: Defined as scores of: 18 or higher on the Aberrant Behavior Checklist-Irritability subscale (ABC-I), and moderate or higher on the Clinical Global Impressions-Severity scale; 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; Written informed consent from parent or legal guardian; Participant and family have the ability to comply with the protocol requirements, in the opinion of the investigator. Exclusion Criteria: Non-English speaking parents; Psychosis; Taking clobazam, mTOR inhibitors (e.g sirolimus, tacrolimus), anti-cancer agents, citalopram >20mg/day, escitalopram >10mg/day.; Abnormal liver function tests: defined as ALT > twice ULN; Abnormal renal function tests: defined as creatinine > ULN Current use of medicinal cannabis, or use in the 4 weeks prior to screening; Pregnant or intending to become pregnant during the study, or breastfeeding; Known allergy to cannabidiol or cannabis products

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cannabidiol 100mg/ml<br>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). | Drug: Cannabidiol Oil<br>* Cannabidiol (CBD) isolate 100mg/ml in MCT oil oral solution, manufactured by THC Pharma<br>|
| Placebo Comparator: Placebo<br>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). | Drug: Placebo<br>* MCT oil and flavoring solution, also manufactured by THC Pharma<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pediatric, intellectual disability, severe behavior problems