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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04821856
Recruitment Status : Recruiting
First Posted : March 30, 2021
Last Update Posted : May 24, 2022
Sponsor:
Collaborators:
Monash University
University of Sydney
Deakin University
Information provided by (Responsible Party):
Murdoch Childrens Research Institute

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 week in children aged 6 - 18 years with Intellectual Disability (ID). Eligible participants will be randomized 1:1 to receive either CBD or placebo.

Condition or disease Intervention/treatment Phase
Intellectual Disability Child Behavior Problem Drug: Cannabidiol Oil Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Placebo-controlled Trial of Cannabidiol to Treat Severe Behavioral Problems in Children and Adolescents With Intellectual Disability
Actual Study Start Date : May 11, 2021
Estimated Primary Completion Date : June 2023
Estimated Study Completion Date : July 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Cannabidiol

Arm Intervention/treatment
Experimental: Cannabidiol 100mg/ml

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

Placebo Comparator: Placebo

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
MCT oil and flavoring solution, also manufactured by THC Pharma




Primary Outcome Measures :
  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 [ Time Frame: At day 64 (end of maintenance treatment period) ]
    This is a 15 item parent-rated questionnaire, used to measure Severe Behavioral Problems in children


Secondary Outcome Measures :
  1. 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 [ Time Frame: At day 64 (end of maintenance treatment period) ]
    43 parent-rated items assessing: Social withdrawal, Stereotypic behavior, Hyperactivity/Noncompliance and Inappropriate Speech

  2. 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 [ Time Frame: At day 64 (end of maintenance treatment period) ]
    This is a single item clinician-rated summary measure of improvement

  3. Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Parent Rated Anxiety Scale-ASD at day 64 [ Time Frame: At day 64 (end of maintenance treatment period) ]
    This is a 25 item parent-rated measure of anxiety in youth with ASD

  4. Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Child & Adolescent Scale of Participation at day 64 [ Time Frame: At day 64 (end of maintenance treatment period) ]
    This is a 20 item parent-rated questionnaire that includes sub-scales for participation in home, school, and community activities

  5. 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 [ Time Frame: At day 64 (end of maintenance treatment period) ]
    This is a 9 item parent-rated, preference-weighted measure used to calculate quality adjusted life years for children

  6. Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Sleep Disturbance Scale for Children at day 64 [ Time Frame: At day 64 (end of maintenance treatment period) ]
    This is a 26 item parent-rated questionnaire assessing sleep difficulties in children

  7. 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 [ Time Frame: At day 64 (end of maintenance treatment period) ]
    This is a 12 item self-report health-related instrument used to calculate quality adjusted life years for parents

  8. 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 [ Time Frame: At day 64 (end of maintenance treatment period) ]
    This is a 25 item parent report measure that includes subscales assessing family interaction, parenting, emotional and material wellbeing, and disability-related support.

  9. Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Depression Anxiety Stress Scale-21 at day 64 [ Time Frame: At day 64 (end of maintenance treatment period) ]
    This is a 21 item self-rated assessment of parent mental health, including symptoms of depression, anxiety and stress

  10. Mean difference between the cannabidiol 100mg/ml and placebo arms on the total score of the Autism Parenting Stress Index at day 64 [ Time Frame: At day 64 (end of maintenance treatment period) ]
    This is a 13 item self-rated measure of 3 categories of stress drivers in parents: core social disability, difficult behavior, physical issues

  11. 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 [ Time Frame: At day 64 (end of maintenance treatment period) ]
    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.


Other Outcome Measures:
  1. Comparing the health sector cost-effectiveness of cannabidiol vs placebo in terms of Aberrant Behavior Checklist - Irritability (ABC-I) scores at day 64 [ Time Frame: At day 64 (end of maintenance treatment period) ]
    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.

  2. Comparing the societal cost-effectiveness of cannabidiol vs placebo in terms of Aberrant Behavior Checklist - Irritability (ABC-I) scores at day 64 [ Time Frame: At day 64 (end of maintenance treatment period) ]
    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.

  3. 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 [ Time Frame: At day 64 (end of maintenance treatment period) ]
    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.

  4. Comparing the societal cost-effectiveness of cannabidiol vs placebo in terms of Quality Adjusted Life Years calculated from the CHU-9D at day 64 [ Time Frame: At day 64 (end of maintenance treatment period) ]
    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.

  5. 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 [ Time Frame: At day 64 (end of maintenance treatment period) ]
    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.

  6. Comparing the societal cost-effectiveness of cannabidiol vs placebo in terms of Quality Adjusted Life Years calculated from the AQOL-4D at day 64 [ Time Frame: At day 64 (end of maintenance treatment period) ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   6 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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, bipolar disorder, major depressive disorder, obsessive compulsive disorder;
  3. Taking clobazam;
  4. Abnormal liver function tests: defined as ALT > twice ULN;
  5. Current use of medicinal cannabis, or use in the 4 weeks prior to screening;
  6. Pregnant or intending to become pregnant during the study, or breastfeeding;
  7. Known allergy to cannabidiol or cannabis products

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04821856


Contacts
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Contact: Daryl Efron +61 (3) 8341 6200 mctrials@mcri.edu.au

Locations
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Australia, New South Wales
The Children's Hospital at Westmead Recruiting
Westmead, New South Wales, Australia, 2145
Contact: Elizabeth Elliott         
Principal Investigator: Elizabeth Elliott         
Australia, Victoria
Monash Children's Hospital Recruiting
Clayton, Victoria, Australia, 3168
Contact: Katrina Williams         
Principal Investigator: Katrina Williams         
Royal Children's Hospital / Murdoch Children's Research Institute Recruiting
Parkville, Victoria, Australia, 3052
Contact: Daryl Efron    +61 (3) 8341 6200    mctrials@mcri.edu.au   
Principal Investigator: Daryl Efron         
Sponsors and Collaborators
Murdoch Childrens Research Institute
Monash University
University of Sydney
Deakin University
Publications:
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Responsible Party: Murdoch Childrens Research Institute
ClinicalTrials.gov Identifier: NCT04821856    
Other Study ID Numbers: RCH HREC 70053
First Posted: March 30, 2021    Key Record Dates
Last Update Posted: May 24, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (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.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Murdoch Childrens Research Institute:
pediatric
intellectual disability
severe behavior problems
Additional relevant MeSH terms:
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Intellectual Disability
Problem Behavior
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Neurodevelopmental Disorders
Mental Disorders
Behavioral Symptoms
Cannabidiol
Anticonvulsants