Cannabinoids for Behavioral Problems in Children With ASD

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

Sponsors

Lead Sponsor: Shaare Zedek Medical Center

Source Shaare Zedek Medical Center
Brief Summary

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.

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.

Overall Status Completed
Start Date 2017-01-01
Completion Date 2018-12-01
Primary Completion Date 2018-10-01
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure 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. 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. At 3 months (end of treatment period)
Secondary Outcome
Measure 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. At 3 months (end of treatment period)
Change in Social Responsiveness Scale scores-2 (SRS-2, parent and teacher rated) at three months 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 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. At onset of each treatment period, at 1 month, 2 months and 3 months (end of treatment period)
Enrollment 150
Condition
Intervention

Intervention Type: Drug

Intervention Name: Cannabinoids - 99% pure cannabinoids mix

Description: 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.

Arm Group Label: Cannabinoids - 99% pure cannabinoids mix

Intervention Type: Drug

Intervention Name: Placebo

Description: Olive oil and flavors solution.

Arm Group Label: Placebo

Intervention Type: Drug

Intervention Name: Cannabinoids - whole plant extract

Description: 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.

Arm Group Label: Cannabinoids - whole plant extract

Eligibility

Criteria:

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.

Gender:

All

Minimum Age:

5 Years

Maximum Age:

21 Years

Healthy Volunteers:

No

Overall Official
Location
Facility: Shaare Zedek Medical Center
Location Countries

Israel

Verification Date

2018-12-01

Responsible Party

Type: Principal Investigator

Investigator Affiliation: Shaare Zedek Medical Center

Investigator Full Name: Dr. Adi Aran

Investigator Title: Director, Neuro-pediatric unit

Has Expanded Access No
Condition Browse
Number Of Arms 3
Arm Group

Label: Cannabinoids - 99% pure cannabinoids mix

Type: Experimental

Description: 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.

Label: Placebo

Type: Placebo Comparator

Description: Oral olive oil and flavors that mimic in texture and flavor the cannabinoids' solution.

Label: Cannabinoids - whole plant extract

Type: Experimental

Description: 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

Acronym CBA
Patient Data Undecided
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

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