Cannabinoids for Behavioral Problems in Children With ASD (CBA)

December 25, 2018 updated by: Dr. Adi Aran, Shaare Zedek Medical Center

Cannabinoids for Behavioral Problems in Autism Spectrum Disorder: A Double Blind, Randomized, Placebo-controlled Trial With Crossover.

This study aims to assess the safety, tolerability and efficacy of cannabinoids mix [cannabidiol (CBD), Δ9-tetrahydrocannabinol (THC) in a 20:1 ratio, BOL Pharma, Israel] for behavioral problems in children and youth with ASD.

Study Overview

Detailed Description

Disruptive behaviors are very common in children and youth with autism spectrum disorder (ASD). Behavioral problems increase social impairment in children with ASD, make interventions more difficult and place considerable strain on families and caregivers. Current treatment is based on behavioral interventions combined with atypical antipsychotics which often have low tolerability and questionable efficacy.

Cannabis exerts profound effects on human social behavior. Research using animal models of ASD indicate a possible dysregulation of the endocannabinoid system, and stress that it may be a novel target for pharmacological interventions. Anecdotal evidence suggest efficacy of various phytocannabinoids in resistant behavioral problems. However controlled human studies are lacking.

Objective: To assess the safety, tolerability and efficacy of cannabinoids mix [cannabidiol (CBD), Δ9-tetrahydrocannabinol (THC) in a 20:1 ratio, BOL Pharma, Israel] for behavioral problems in children and youth with ASD.

Setting: A double blind randomized placebo-controlled trial with crossover.

Methods: One hundred and fifty participants, ages 5-21 years, with ASD and moderate to severe refractory behavioral problems will be randomized to receive 1 out of 3 treatments for 12-weeks and cross-over to another treatment in a second 12 weeks period. Treatment options are: (1) oral placebo (2) cannabis extract, contains cannabidiol and Δ9-tetrahydrocannabinol in a 20:1 ratio, at a cannabidiol dose of 10 mg/kg/d and (3) pure cannabidiol and Δ9-tetrahydrocannabinol in the same ratio and dose.

Outcomes and measures: Two co-primary endpoints will compare the whole plant extract treatment to the placebo treatment on a within subject design. 1) The change from baseline Home Situations Questionnaire-ASD score after 3 months of treatment (HSQ-ASD; a parent rated assessment of disruptive behavior). 2) The Clinical Global Impression- improvement (CGI-I; a clinician rated assessment of improvement in disruptive behavior following treatment)

Secondary efficacy outcomes include:

  • Within subject differences between the placebo condition and the pure cannabinoids condition and between the whole plant extract condition and the pure cannabinoids condition in the change from baseline HSQ-ASD score after 3 months of treatment and in the CGI-I.
  • Within subject differences between each pair of the 3 conditions in the Clinical Global Impression- drug effect (CGI-D).
  • Within subject differences between each pair of the 3 conditions in the change from baseline after 3 months of treatment in: Social Responsiveness Scale (SRS) parent and teacher rated, Child Behavior Checklist (CBCL) and autism parenting stress index (APSI).

Safety endpoints will include the proportion of patients with adverse events measured by the investigators and the Liverpool Adverse Events Profile (modified).

Exploratory measures are: markers of the endocannabinoid system in the patients' blood and possible correlation to phytocannabinoids bioavailability and treatment response, change from baseline at the end of treatment in BMI and Children's Sleep Habits Questionnaire (CSHQ) score and quality of parent- child interaction during the study (Emotional Availability- EA).

Long term safety, tolerability and efficacy of cannabidiol-rich medical cannabis will be assessed after 12 and 24 months of open treatment, in a subgroup of patients who will apply for medical license to use cannabis after completing the study.

Study Type

Interventional

Enrollment (Actual)

150

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Israel
      • Jerusalem, Israel
        • Shaare Zedek Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

5 years to 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria: (both are needed)

  • ASD diagnosis (Diagnostic and Statistical Manual of Mental Disorders [Fifth Edition; DSM-V]
  • Moderate or greater behavioral problems as measured by a rating of moderate or higher (≥4) on the Clinical Global Impression-Severity (CGI-S)

Exclusion Criteria:

  • Planned changes in existing interventions for the duration of the trial or such a change in the last 4 weeks.
  • Current treatment with cannabis based therapy or such a treatment in the last 3 months.
  • Heart, liver, renal or hematological disorders
  • History of psychotic disorder in a first degree relative.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cannabinoids - 99% pure cannabinoids mix
Oral cannabinoids mix [cannabidiol (CBD), Δ9-tetrahydrocannabinol (THC) in a 20:1 ratio] at 1 mg/kg cannabidiol per day, up-titrated until intolerance or to a maximum dose of 10 mg/kg CBD per day, divided to 3 daily doses, for 3 months.
99% pure cannabidiol (CBD) and 99% pure Δ9-tetrahydrocannabinol (THC) in a 20:1 ratio (B.O.L Pharma, Israel), in a 160/8.0 mg per mL (CBD/THC) olive oil-based solution.
Placebo Comparator: Placebo
Oral olive oil and flavors that mimic in texture and flavor the cannabinoids' solution.
Olive oil and flavors solution.
Experimental: Cannabinoids - whole plant extract
Oral cannabinoids mix [cannabidiol (CBD), Δ9-tetrahydrocannabinol (THC) in a 20:1 ratio] at 1 mg/kg cannabidiol per day, up-titrated until intolerance or to a maximum dose of 10 mg/kg CBD per day, divided to 3 daily doses, for 3 months
Whole plant extract enriched with cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) to achieve 20:1 ratio (B.O.L Pharma, Israel), in a 160/8.0 mg per mL (CBD/THC) olive oil-based solution.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline Home Situations Questionnaire-Autism Spectrum Disorder (HSQ-ASD) score, at three months. Within subject difference between the placebo condition and the whole plant extract condition.
Time Frame: At onset of each treatment period, at 1 month, 2 months and 3 months (end of treatment period)
This is a 24-item parent-rated measure of noncompliant behavior in children with ASD
At onset of each treatment period, at 1 month, 2 months and 3 months (end of treatment period)
Clinical Global Impression-Improvement scores (CGI-I ) at three months. Within subject difference between the placebo condition and the whole plant extract condition.
Time Frame: At 3 months (end of treatment period)
This is a 7-point scale designed to measure overall improvement from baseline (CGI-I).
At 3 months (end of treatment period)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Global Impression-Improvement scores (CGI-I ) at three months. Within subject differences between the placebo condition and the pure cannabinoids condition and between the whole plant extract condition and the pure cannabinoids condition.
Time Frame: At 3 months (end of treatment period)
This is a 7-point scale designed to measure overall improvement from baseline
At 3 months (end of treatment period)
Change in Social Responsiveness Scale scores-2 (SRS-2, parent and teacher rated) at three months
Time Frame: At onset of each treatment period and at 3 months (end of treatment period)
This is a 65 item, caregiver (pSRS) or teacher (tSRS) questionnaire, used to determine the severity of social deficit exhibited by participants with ASD. The SRS contains five subscales: Social Awareness, Social Cognition, Social Communication, Social Motivation, and Autistic Mannerisms, which respectively measure the ability to recognize social cues, the ability to interpret social cues, the ability to use expressive verbal and nonverbal language skills, the ability to engage in social-interpersonal behaviors, and the tendency to display stereotypical behaviors and restricted interests characteristic of autism
At onset of each treatment period and at 3 months (end of treatment period)
Change in Autism Parenting Stress Index (APSI) score, at three months
Time Frame: At onset of each treatment period, at 1 month, 2 months and 3 months (end of treatment period)
This is a 13-item parent rated measure designed to assess the effect of interventions to control disruptive behavior in children with ASD on parenting stress.
At onset of each treatment period, at 1 month, 2 months and 3 months (end of treatment period)
Change from baseline Home Situations Questionnaire-Autism Spectrum Disorder (HSQ-ASD) score, at three months.
Time Frame: At onset of each treatment period, at 1 month, 2 months and 3 months (end of treatment period)
This is a 24-item parent-rated measure of noncompliant behavior in children with ASD. Within subject differences between the placebo condition and the pure cannabinoids condition and between the whole plant extract condition and the pure cannabinoids condition.
At onset of each treatment period, at 1 month, 2 months and 3 months (end of treatment period)

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Modified Liverpool Adverse Events Profile (LAEP)
Time Frame: At onset of each treatment period, at 1 month, 2 months and 3 months (end of treatment period)
Tolerability and adverse effects will be assessed using this modified Liverpool Adverse Events Profile (LAEP) that includes all 19 items of the original LAEP and another 15 items to cover all reported significant side effects of CBD and THC in former studies.
At onset of each treatment period, at 1 month, 2 months and 3 months (end of treatment period)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Adi Aran, MD, Shaare Zedek Medical Center
  • Principal Investigator: Varda Gross, Shaare Zedek Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2017

Primary Completion (Actual)

October 1, 2018

Study Completion (Actual)

December 1, 2018

Study Registration Dates

First Submitted

November 1, 2016

First Submitted That Met QC Criteria

November 2, 2016

First Posted (Estimate)

November 6, 2016

Study Record Updates

Last Update Posted (Actual)

December 27, 2018

Last Update Submitted That Met QC Criteria

December 25, 2018

Last Verified

December 1, 2018

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact [email protected]. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Autistic Disorder

Clinical Trials on Cannabinoids - 99% pure cannabinoids mix