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Trial registered on ANZCTR


Registration number
ACTRN12618001852246
Ethics application status
Approved
Date submitted
7/11/2018
Date registered
14/11/2018
Date last updated
11/03/2019
Date data sharing statement initially provided
14/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Does cannabidiol reduce severe behavioural problems in youth with intellectual disability? Feasibility and pilot randomised placebo-controlled trial.
Scientific title
Pilot study of cannabidiol (CBD) in children with Intellectual Disability (ID) and Severe Behavioural Problems (SBP)
Secondary ID [1] 296538 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Intellectual Disability 310318 0
Severe Behaviour Problems 310319 0
Condition category
Condition code
Mental Health 309051 309051 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Tilray Cannabis Extract - 98% Cannabidiol in oil.
Oral administration of liquid solution via dropper. 20mg/kg/day, with a ceiling dose of 1000mg/day.
The starting dose of CBD or placebo will be 5 mg/kg/day and will be administered orally twice daily in doses of 2.5 mg/kg. The dose of CBD or placebo will be increased in increments of 5 mg/kg/day every 3 days for 9 days up to the maintenance dose of 20 mg/kg/day (Up Titration Phase). Participants will continue to receive CBD at the maintenance dose for 56 days (8 week Maintenance Phase). On completion of the maintenance phase the dose of CBD will be decreased in increments of 5mg/kg/day for 9 days at which time CBD administration will cease.
Participants will return any unused study drug, as well as empty medicine bottles, to the trial Pharmacy, who will weigh the bottles to obtain an estimate of treatment compliance.
Intervention code [1] 312843 0
Treatment: Drugs
Comparator / control treatment
The control group will receive placebo grapeseed oil which is indistinguishable from the active medication in appearance, smell and taste (Tilray, Canada).
Control group
Placebo

Outcomes
Primary outcome [1] 308014 0
Recruitment feasibility: Recruitment rate (% of eligible participants enrolled)
Timepoint [1] 308014 0
Data collected throughout the recruitment period or until the desired sample size has been recruited.
Primary outcome [2] 308015 0
Acceptability of study procedures (tolerability of the study medication, study visits, blood tests, parent questionnaire completion): assessed through a parent-rated questionnaire that was designed specifically for this study.
Timepoint [2] 308015 0
30 days post-cessation of the study medication (104 days after randomisation).
Primary outcome [3] 308016 0
Protocol completion: Withdrawals and treatment discontinuations will be recorded by the investigators with reasons.
Timepoint [3] 308016 0
Data will be collected throughout the duration of the study, from commencement to 74 days post-commencement.
Secondary outcome [1] 353655 0
Safety outcomes: the number and severity of treatment-emergent adverse events and serious adverse events will be recorded using the Monitoring of Side Effects Scale (MOSES) completed by the parent or guardian. MOSES is an 83-item measure which includes all of the known side-effects of CBD, as well as those of psychotropic medications.
Timepoint [1] 353655 0
Data collected at Day 1, 10 and 66.
Secondary outcome [2] 353656 0
Adverse events will be will be documented from diary cards, physical examination findings, and clinically significant lab results.
The most common adverse effects associated with this product are somnolence, diarrhoea and decreased appetite
Timepoint [2] 353656 0
Diary card data will be recorded daily from Day 1 through to Day 104 (end of study). Physical examination and lab findings will be collected at baseline, Day 10 & 66.
Secondary outcome [3] 353913 0
Medication regimen adherence (primary outcome): This will be collected through parent report on diary cards.
Timepoint [3] 353913 0
Medication dosing will be recorded on diary cards daily from Day 1 through to Day 74.
Secondary outcome [4] 353914 0
Medication adherence (primary outcome): Will be further checked by trials pharmacy staff weighing returned medication bottles.
Timepoint [4] 353914 0
Medication bottles will be weighed at Day 10, 38, 66 and 74.

Eligibility
Key inclusion criteria
Each patient must meet all of the following criteria to be enrolled in this study:
1. Males and females aged 8 – 16 years of age;
2. DSM-5 diagnosis of ID.
a. Full scale IQ < 70 on standardized cognitive assessment on verified records of testing performed within two years of enrolment. 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.
b. Deficit in adaptive function (basis for severity rating of ID in DSM-5) in at least one activity of life: Vineland Adaptive Behavior Scales completed by interview with the parent or guardian; derives scores in Communication, Daily Living Skills and Socialization domains, and a Global Adaptive score.
3. SBP: Defined as:
a. scores of 18 or higher on the Aberrant Behavior Checklist-Irritability subscale (ABC-I), and
b. moderate or higher on the Clinical Global Impressions-Severity scale.
4. Consistent pattern of frequent SBP symptoms for > 3 months (parent interview).
5. No changes in either medication or other interventions in the 4 weeks prior to randomization.
6. Written informed consent from parent or legal guardian.
7. Has the ability to comply with the protocol requirements, in the opinion of the investigator.
Minimum age
8 Years
Maximum age
16 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Non-English speaking parents.
2. Psychosis, bipolar disorder, major depressive disorder, obsessive compulsive disorder.
3. Taking anti-epileptic medications which interact with CBD (e.g. clobazam, topiramate, zonisamide)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation will be concealed from the investigators throughout the trial. A randomisation schedule will be generated by an independent statistician and provided to the trials Pharmacy.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
This study will utilise simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
The primary objective of this pilot study is to evaluate all elements of the study design (recruitment strategy, tolerability of the study medication, study duration, study procedures and outcome measures) to assess if they are acceptable and feasible for the conduct of a full-scale randomized clinical trial of CBD to reduce SBP in children with ID.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 12367 0
The Royal Childrens Hospital - Parkville
Recruitment postcode(s) [1] 24630 0
3052 - Parkville

Funding & Sponsors
Funding source category [1] 301119 0
Other
Name [1] 301119 0
Murdoch Children's Research Institute
Address [1] 301119 0
50 Flemington Road
Parkville, Victoria, 3052
Country [1] 301119 0
Australia
Primary sponsor type
Other
Name
Murdoch Children's Research Institute
Address
50 Flemington Road
Parkville, Victoria, 3052
Country
Australia
Secondary sponsor category [1] 300735 0
None
Name [1] 300735 0
Address [1] 300735 0
Country [1] 300735 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301869 0
HREC Royal Children's Hospital
Ethics committee address [1] 301869 0
Royal Children's Hospital
50 Flemington Road
Parkville, Vic, 3052
Ethics committee country [1] 301869 0
Australia
Date submitted for ethics approval [1] 301869 0
20/09/2018
Approval date [1] 301869 0
28/11/2018
Ethics approval number [1] 301869 0
38236

Summary
Brief summary
This is a single site, double-blind, parallel group, randomized, placebo-controlled pilot study of 10 participants comparing 98% cannabidiol oil (CBD) with placebo in reducing Severe Behavioural Problems (SBP) in children aged 8 – 16 years with Intellectual Disability (ID). Eligible participants will be randomized 1:1 to receive either CBD or placebo.

The primary objective of this pilot study is to evaluate all elements of the study design (recruitment strategy, tolerability of the study medication, study duration, study procedures and outcome measures) to assess if they are acceptable and feasible for the conduct of a full-scale randomized clinical trial of CBD to reduce SBP in children with ID.

The secondary objectives of this study are to assess the safety of the administration of oral CBD in children aged 8 -16 years with ID and SBP.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 88382 0
A/Prof Daryl Efron
Address 88382 0
Murdoch Children's Research Institute
50 Flemington Rd
Parkville, Vic, 3052
Country 88382 0
Australia
Phone 88382 0
+61 -3- 9345 4563
Fax 88382 0
Email 88382 0
daryl.efron@mcri.edu.au
Contact person for public queries
Name 88383 0
A/Prof Daryl Efron
Address 88383 0
Murdoch Children's Research Institute
50 Flemington Rd
Parkville, Vic, 3052
Country 88383 0
Australia
Phone 88383 0
+61 -3- 9345 4563
Fax 88383 0
Email 88383 0
daryl.efron@mcri.edu.au
Contact person for scientific queries
Name 88384 0
A/Prof Daryl Efron
Address 88384 0
Murdoch Children's Research Institute
50 Flemington Rd
Parkville, Vic, 3052
Country 88384 0
Australia
Phone 88384 0
+61 -3- 9345 4563
Fax 88384 0
Email 88384 0
daryl.efron@mcri.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The primary objective of this pilot study is to evaluate all elements of the study design (recruitment strategy, tolerability of the study medication, study duration, study procedures and outcome measures) to assess if they are acceptable and feasible for the conduct of a full-scale randomized clinical trial of CBD to reduce SBP in children with ID. Individual participant data will not be meaningful for this study.
What supporting documents are/will be available?
No other documents available
Summary results
No Results