Back to results

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

Primary Purpose

Intellectual Disability, Child Behavior Problem

Status

Recruiting

Phase

Phase 2

Locations

Australia

Study Type

Interventional

Intervention

Cannabidiol Oil

Placebo

About this trial

This is an interventional treatment trial for Intellectual Disability focused on measuring pediatric, intellectual disability, severe behavior problems

Eligibility Criteria

6 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Males and females aged 6 - 18 years of age;
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.
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;
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, bipolar disorder, major depressive disorder, obsessive compulsive disorder;
Taking clobazam;
Abnormal liver function tests: defined as ALT > twice 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

Sites / Locations

The Children's Hospital at WestmeadRecruiting
Monash Children's HospitalRecruiting
Royal Children's Hospital / Murdoch Children's Research InstituteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Cannabidiol 100mg/ml

Placebo

Arm Description

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).

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).

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

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

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

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

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

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

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

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.

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

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

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.

Full Information

NCT ID

NCT04821856

First Posted

March 25, 2021

Last Updated

August 2, 2023

Sponsor

Murdoch Childrens Research Institute

Collaborators

Monash University, University of Sydney, Deakin University

1. Study Identification

Unique Protocol Identification Number

NCT04821856

Brief Title

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

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Recruiting

Study Start Date

May 11, 2021 (Actual)

Primary Completion Date

June 2024 (Anticipated)

Study Completion Date

July 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Murdoch Childrens Research Institute

Collaborators

Monash University, University of Sydney, Deakin University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Intellectual Disability, Child Behavior Problem

Keywords

pediatric, intellectual disability, severe behavior problems

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

140 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Cannabidiol 100mg/ml

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Cannabidiol Oil

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

MCT oil and flavoring solution, also manufactured by THC Pharma

Primary Outcome Measure Information:

Title

Mean difference between the cannabidiol 100mg/ml and placebo arms on the Aberrant Behavior Checklist-Irritability (ABC-I) subscale total score at day 64

Description

This is a 15 item parent-rated questionnaire, used to measure Severe Behavioral Problems in children

Time Frame

At day 64 (end of maintenance treatment period)

Secondary Outcome Measure Information:

Title

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

Description

43 parent-rated items assessing: Social withdrawal, Stereotypic behavior, Hyperactivity/Noncompliance and Inappropriate Speech

Time Frame

At day 64 (end of maintenance treatment period)

Title

Description

This is a single item clinician-rated summary measure of improvement

Time Frame

At day 64 (end of maintenance treatment period)

Title

Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Parent Rated Anxiety Scale-ASD at day 64

Description

This is a 25 item parent-rated measure of anxiety in youth with ASD

Time Frame

At day 64 (end of maintenance treatment period)

Title

Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Child & Adolescent Scale of Participation at day 64

Description

This is a 20 item parent-rated questionnaire that includes sub-scales for participation in home, school, and community activities

Time Frame

At day 64 (end of maintenance treatment period)

Title

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

Description

This is a 9 item parent-rated, preference-weighted measure used to calculate quality adjusted life years for children

Time Frame

At day 64 (end of maintenance treatment period)

Title

Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Sleep Disturbance Scale for Children at day 64

Description

This is a 26 item parent-rated questionnaire assessing sleep difficulties in children

Time Frame

At day 64 (end of maintenance treatment period)

Title

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

Description

This is a 12 item self-report health-related instrument used to calculate quality adjusted life years for parents

Time Frame

At day 64 (end of maintenance treatment period)

Title

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

Description

This is a 25 item parent report measure that includes subscales assessing family interaction, parenting, emotional and material wellbeing, and disability-related support.

Time Frame

At day 64 (end of maintenance treatment period)

Title

Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Depression Anxiety Stress Scale-21 at day 64

Description

This is a 21 item self-rated assessment of parent mental health, including symptoms of depression, anxiety and stress

Time Frame

At day 64 (end of maintenance treatment period)

Title

Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Autism Parenting Stress Index at day 64

Description

This is a 13 item self-rated measure of 3 categories of stress drivers in parents: core social disability, difficult behavior, physical issues

Time Frame

At day 64 (end of maintenance treatment period)

Title

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

Description

Time Frame

At day 64 (end of maintenance treatment period)

Other Pre-specified Outcome Measures:

Title

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

Description

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.

Time Frame

At day 64 (end of maintenance treatment period)

Title

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

Description

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.

Time Frame

At day 64 (end of maintenance treatment period)

Title

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

Description

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.

Time Frame

At day 64 (end of maintenance treatment period)

Title

Comparing the societal cost-effectiveness of cannabidiol vs placebo in terms of Quality Adjusted Life Years calculated from the CHU-9D at day 64

Description

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.

Time Frame

At day 64 (end of maintenance treatment period)

Title

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

Description

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.

Time Frame

At day 64 (end of maintenance treatment period)

Title

Comparing the societal cost-effectiveness of cannabidiol vs placebo in terms of Quality Adjusted Life Years calculated from the AQOL-4D at day 64

Description

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.

Time Frame

At day 64 (end of maintenance treatment period)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Years

Maximum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Daryl Efron

Phone

+61 (3) 8341 6200

mctrials@mcri.edu.au

Facility Information:

Facility Name

The Children's Hospital at Westmead

City

Westmead

State/Province

New South Wales

ZIP/Postal Code

2145

Country

Australia

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Elizabeth Elliott

First Name & Middle Initial & Last Name & Degree

Elizabeth Elliott

Facility Name

Monash Children's Hospital

City

Clayton

State/Province

Victoria

ZIP/Postal Code

3168

Country

Australia

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Katrina Williams

First Name & Middle Initial & Last Name & Degree

Katrina Williams

Facility Name

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

City

Parkville

State/Province

Victoria

ZIP/Postal Code

3052

Country

Australia

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Daryl Efron

Phone

+61 (3) 8341 6200

mctrials@mcri.edu.au

First Name & Middle Initial & Last Name & Degree

Daryl Efron

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

The de-identified data set collected for this analysis of the RCT of CBD in children and adolescents with ID will be available six months after publication of the primary outcome. The study protocol and analysis plan will also be available. The data must be obtained from the Murdoch Children's Research Institute. Prior to releasing any data the following are required: a data access agreement must be signed between relevant parties, the 'RCT of CBD in children and adolescents with ID' Trial Steering Committee must see and approve the data analysis plan describing how the data will be analysed, there must be an agreement around appropriate acknowledgment and any additional costs involved must be covered. Should the Trial Steering Committee be unavailable, this role is delegated to the Murdoch Children's Research Institute. Data will only be shared with a recognized research organisation which has approved the proposed analysis plan.

IPD Sharing Time Frame

6 months after publication of primary outcome

IPD Sharing Access Criteria

1) Data access agreement; 2) approval by Trial Steering Committee; 3) recognized research institutions.

Citations:

PubMed Identifier

32152170

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.

Results Reference

background

PubMed Identifier

32478863

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.

Results Reference

background

Learn more about this trial

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

We'll reach out to this number within 24 hrs