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

NCT04821856 | Completed Phase 2 DMC

• 1 other identifier: RCH HREC 70053
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 3

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.

Conditions

Intellectual Disability; Child Behavior Problem

Keywords

pediatric; intellectual disability; severe behavior problems

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• 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

  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

  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

  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

  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

  At day 64 (end of maintenance treatment period)

Other Outcomes (6)

• Comparing the health sector cost-effectiveness of cannabidiol vs placebo in terms of Aberrant Behavior Checklist - Irritability (ABC-I) scores at day 64

  At day 64 (end of maintenance treatment period)

• Comparing the societal cost-effectiveness of cannabidiol vs placebo in terms of Aberrant Behavior Checklist - Irritability (ABC-I) scores at day 64

  At day 64 (end of maintenance treatment period)

• 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

  At day 64 (end of maintenance treatment period)

Study Arms (2)

Cannabidiol 100mg/ml

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Cannabidiol Oil DRUG

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

Cannabidiol 100mg/ml

Placebo DRUG

MCT oil and flavoring solution, also manufactured by THC Pharma

Placebo

Eligibility Criteria

• Age: 6 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Murdoch Childrens Research Institute: lead
• Monash University: collaborator
• University of Sydney: collaborator
• Deakin University: collaborator

Study Sites (3)

The Children's Hospital at Westmead

Westmead, New South Wales, 2145, Australia

Location

Monash Children's Hospital

Clayton, Victoria, 3168, Australia

Location

Royal Children's Hospital / Murdoch Children's Research Institute

Parkville, Victoria, 3052, Australia

Location

Related Publications (2)

• 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.

  PMID: 32152170 BACKGROUND

• 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.

  PMID: 32478863 BACKGROUND

MeSH Terms

Conditions

Intellectual Disability; Mental Disorders

Interventions

Cannabidiol

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurodevelopmental Disorders

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Study Officials

• Daryl Efron

  Murdoch Childrens Research Institute

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2021
• First Posted: March 30, 2021
• Study Start: May 11, 2021
• Primary Completion: July 9, 2025
• Study Completion: August 19, 2025
• Last Updated: September 3, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 6 months after publication of primary outcome
• Access Criteria: 1\) Data access agreement; 2) approval by Trial Steering Committee; 3) recognized research institutions.

Locations

AU (3)