Cannabinoids for Behavioral Problems in Children With ASD

NCT ID: NCT02956226

Last Updated: 2018-12-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

150 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-01-31

Study Completion Date

2018-12-31

Brief Summary

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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

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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.

Conditions

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Autistic Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

Cannabinoids - 99% pure cannabinoids mix

Intervention Type DRUG

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

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Olive oil and flavors solution.

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

Group Type EXPERIMENTAL

Cannabinoids - whole plant extract

Intervention Type DRUG

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.

Interventions

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Cannabinoids - 99% pure cannabinoids mix

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.

Intervention Type DRUG

Placebo

Olive oil and flavors solution.

Intervention Type DRUG

Cannabinoids - whole plant extract

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.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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.
Minimum Eligible Age

5 Years

Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Shaare Zedek Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Dr. Adi Aran

Director, Neuro-pediatric unit

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Adi Aran, MD

Role: PRINCIPAL_INVESTIGATOR

Shaare Zedek Medical Center

Varda Gross

Role: PRINCIPAL_INVESTIGATOR

Shaare Zedek Medical Center

Locations

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Shaare Zedek Medical Center

Jerusalem, , Israel

Site Status

Countries

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Israel

References

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Aran A, Harel M, Cassuto H, Polyansky L, Schnapp A, Wattad N, Shmueli D, Golan D, Castellanos FX. Cannabinoid treatment for autism: a proof-of-concept randomized trial. Mol Autism. 2021 Feb 3;12(1):6. doi: 10.1186/s13229-021-00420-2.

Reference Type DERIVED
PMID: 33536055 (View on PubMed)

Other Identifiers

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CBA

Identifier Type: -

Identifier Source: org_study_id