Clinical trial NCT04517799: Trial of Cannabidiol to Treat Severe Behavior Problems in Children With Autism
Official title: A Double-Blind, Crossover Trial of Cannabidiol to Treat Severe Behavior Problems in Children With Autism
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Autism
Autism Spectrum Disorder
Keywords: cannabidiol
CBD
autism
autism spectrum disorder
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
Collaborators: name: Wholistic Research and Education Foundation
name: Center for Medicinal Cannabis Research
First posted: 2020-08-18
Enrollment: 42
Sex: MALE
Minimum age (years): 7
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: There are very few treatments that are effective in reducing severe behavioral problems associated with autism. These behaviors include aggressive and self-harm behaviors, frequent repetitive behaviors and severe hyperactivity. This study is being conducted to determine whether cannabidiol can reduce any or all of these problem behaviors.

Detailed description: Children with autism spectrum disorders (ASD) may have severe behavior problems, including aggression, self-injurious behaviors, severe and persistent stereotypic behaviors, and extreme hyperactivity, which limit their ability to function socially and academically and are often disruptive to family life as well. Cannabidiol (CBD), a compound originally derived from the cannabis plant but without the psychoactive effects found in cannabis, has been shown to be safe and effective in the treatment of children with severe epilepsy. Two non-controlled studies using CBD from local sources have demonstrated improvements in behavior in children with autism. Parents of autistic children have been using CBD products in an unregulated fashion with unknown dosing with anecdotal reports of improved behavior. This study will use EPIDIOLEX (EPX), a purified CBD oral solution that was FDA approved in June 2018 to treat severe forms of pediatric epilepsy. Study subjects will be 30 boys between 7 and 14 years of age with autism who have severe behavior problems. Every child will undergo baseline clinical evaluation, neuropsychological, behavioral, cognitive, and language testing, will have a test of brain wave activity (EEG) and a brain MRI scan. parents will complete questionnaires on various aspects of their child's behavior. Fifteen children will receive CBD for 8 weeks and 15 will receive a placebo that looks and tastes similar to the CBD (Period 1). All of the baseline tests and questionnaires will then be repeated. After a 4 week washout period, behavioral and cognitive tests and questionnaires will be repeated and then the treatments will be reversed (Period 2). At the end of 8 weeks, all of the baseline tests and questionnaires will be repeated. Study personnel and parents will be blinded to the treatment status of each child. Statistical analyses will be used to determine whether there are significant differences between baseline testing and results after placebo or CBD treatment. Types and severities of adverse events will be tracked to provide information about the safety and tolerability of CBD in this population. If CBD is found to be safe and effective in treating the behavioral problems associated with autism, this would be a major new tool in the treatment of those children that could lead to improved functioning and quality of life for the affected individuals and their families.

Eligibility criteria: Inclusion Criteria:

* Boys ages 7-14 years
* Confirmed diagnosis of autism based on ADOS testing
* Autism severity assessed as severe with substantial behavioral problems

Severity of symptoms will be based on a number of criteria:

1. Aggressive and/or self-injurious (SIBs) behaviors occur almost daily (more than 6 times per week) in any situation (home, school, clinic, etc.).
2. Frequent (daily), persistent (lasting at least 5-10 minutes and repeated through the day) stereotypies (repetitive behaviors such as hand flapping, running in circles, jumping repeatedly, waving fingers in front of eyes)
3. Pervasive hyperactivity (child is so physically active that he cannot sit for meals or school work, is moving all the time, jumping off furniture, climbing onto furniture, etc.)
4. One of more of the above activities is deemed to contribute significantly to child's inability to function by parental report and with clinician agreement based on history and/or direct observation

Exclusion Criteria:

* the presence of epilepsy
* a known genetic condition such as tuberous sclerosis
* other significant health issues such as cardiac disease, presence of known congenital brain malformation, or a history of central nervous system infection.
* children who are on anticonvulsant medications such as clobazam or valproic acid will also be excluded because of potential drug-drug interactions. At the time of screening, each child's medication list will be checked for drugs that are known to cause interactions with cannabidiol.
* children with an allergy to any components of the study drug
* children who are taking CBD from another source, unless parents are willing to stop the treatment for at least 4 weeks prior to entering the study. CBD and other cannabinoid blood levels will be performed at baseline and if CBD is detected in the blood, the child will be not be included in the study.
* children who might travel out of the area for a significant time during the study
* children who recently participated in another investigational drug trial may be excluded

Primary outcomes:
measure: Total Score on Repetitive Behavior Scale-Revised (RBS-R)
timeFrame: Start to finish of period 1 (8 weeks) and start to finish of period 2 (8 weeks)
measure: Total Score on Child Behavior Checklist (CBCL)
timeFrame: Start to finish of period 1 (8 weeks) and start to finish of period 2 (8 weeks)
measure: Autism Diagnostic Observation Scale- 2 (ADOS-2)
timeFrame: Start to finish of period 1 (8 weeks) and start to finish of period 2 (8 weeks)
Secondary outcomes:
measure: Total Score on Aberrant Behavior Checklist (ABC)
timeFrame: Start to finish of period 1 (8 weeks) and start to finish of period 2 (8 weeks)
measure: Total Score on Social Responsiveness Scale
timeFrame: Start to finish of period 1 (8 weeks) and start to finish of period 2 (8 weeks)
measure: Total Score on Peabody Picture Vocabulary test (PPVT-4)
timeFrame: Start to finish of period 1 (8 weeks) and start to finish of period 2 (8 weeks)
measure: Total Score on Expressive One Word Picture Vocabulary test, Fourth Edition (EOWPVT-4)
timeFrame: Start to finish of period 1 (8 weeks) and start to finish of period 2 (8 weeks)
measure: Total Score on Children's Sleep Habits Questionnaire (CSHQ)
timeFrame: Start to finish of period 1 (8 weeks) and start to finish of period 2 (8 weeks)
Other outcomes:
measure: Magnetic Resonance Spectroscopy
timeFrame: Start to finish of period 1 (8 weeks) and start to finish of period 2 (8 weeks)
Locations:
city: La Jolla
country: United States
facility: University of California San Diego
state: California
Study officials:
affiliation: University of California, San Diego
name: Doris Trauner, MD
role: PRINCIPAL_INVESTIGATOR
References: