Clinical trial NCT04520685: CASCADE: CAnnabidiol Study in Children With Autism Spectrum DisordEr
Official title: CAnnabidiol Study in Children With Autism Spectrum DisordEr (CASCADE): A Double-Blind, Placebo-Controlled Study to Investigate Efficacy and Safety of Cannabidiol in Children and Adolescents With Autism
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Autism Spectrum Disorder
Keywords: CBD
cannabidiol
ASD
autism spectrum disorder
autism
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2020-08-20
Enrollment: 86
Sex: ALL
Minimum age (years): 5
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: For this study, participants will be randomly assigned to one of the following groups:

1. Group A will receive cannabidiol for the first 12 weeks of the study and placebo for the last 15 weeks.
2. Group B will receive placebo for the first 15 weeks of the study and cannabidiol for the last 12 weeks
3. Group C will receive cannabidiol throughout the entire 27 weeks of treatment
Primary purpose: TREATMENT

Brief summary: This is a randomized, placebo-controlled study but all study participants will receive the active study medication at some point during the study for at least 12 weeks, and some children with receive CBD for the entire study.

Detailed description: Autism spectrum disorder (ASD) is a relatively common neurodevelopmental disorder manifest by social communication deficits and restricted and repetitive interests. Individuals with ASD often have behavioral issues and psychiatric comorbidities which can be very hard to manage. Currently, there are only two FDA approved medications (aripiprazole and risperidone) for the treatment of irritability in ASD. Both medications have the potential for side effects and are not tolerated in all children with ASD. Anecdotal and some preliminary studies suggest that cannabidiol (CBD), a non-psychoactive cannabinoid in the marijuana plant, may lead to improvements in symptoms of ASD including irritability, aggressive behaviors, and anxiety.

In this study the investigators will test whether CBD leads to differences in behaviors commonly associated with ASD. The main behavioral problems investigators will study are irritability and aggressive behavior. This study will also measure changes in other behaviors seen in ASD such as anxiety, social interaction difficulties, repetitive behaviors, attentional problems, hyperactivity, repetitive behaviors, and quality of life. Study investigators will also test whether there are any important side effects of CBD in children and adolescents with ASD.

Eligibility criteria: Inclusion Criteria:

* Male or female children and adolescents aged 5-17 years, inclusive, at the time of screening.
* Judged by the investigator to be in good health at screening based upon the results of a medical history, physical examination, 12-lead ECG, and clinical laboratory test results.
* Patients must have a previous documented diagnosis of ASD by a medical or psychological professional.
* Patients must be assessed by the Investigator as being moderately to severely impacted due to ASD
* Patients who are taking psychotropic medication(s) should be on a stable regimen of no more than 2 medications for at least 4 weeks preceding study Screening and must maintain that regimen throughout the study. Psychotropic medications include (but are not limited to) antipsychotics, antidepressants, mood stabilizers, anxiolytics, and ADHD medications.
* Patients with a history of seizure disorders must currently be receiving treatment with a stable regimen of one or two AEDs, or must be seizure-free for 1 year if not currently receiving AEDs.
* Patients with seizures should be on a stable regimen for the 3 months preceding study enrollment of no more than 2 of the permitted anti-epileptic drugs (AEDs). Patients must remain on a stable AED dose throughout the study.
* If patients are receiving non-pharmacological educational, behavioral, and/or dietary interventions or therapies, they must be stable and have been doing so for 2 months prior to screening. Changes with school breaks are expected and do not apply.
* Patients must have a BMI of between 12-32 kg/m2 (inclusive).
* Females of childbearing potential and must have a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test at all designated visits.
* Patients/caregivers agree to abide by all study restrictions and comply with all study procedures.
* Parents/caregivers must be able to read and respond to questions and questionnaires in English.
* Patients/caregivers must be adequately informed of the nature and risks of the study and give written informed consent prior to screening.
* Parents/caregiver(s) must provide written consent to assist in study drug administration.
* In the Investigator's opinion, patients/caregivers are reliable and willing and able to comply with all protocol requirements and procedures (including scheduled visits and confinement periods).

Exclusion Criteria:

* Adolescent females who are pregnant, nursing, or planning a pregnancy. Females of childbearing potential and male patients with a partner of childbearing potential who are unwilling or unable to use standard acceptable methods of contraception (including abstinence, hormonal contraception, diaphragm, cervical cap, vaginal sponge, condom, or intrauterine device) for the duration of the study and for 1 month after the last dose of study medication.
* History of significant allergic condition, significant drug-related hypersensitivity, or allergic reaction to any compound or chemical class related to CBD (Epidiolex) or its ingredients.
* Exposure to any investigational drug or device \< 30 days prior to screening, or plans to take another investigational drug at any time during the study.
* Use of any THC or CBD-containing product within 4 weeks of Screening Visit, planned use during the study, or positive THC urine test at screening.
* Patient is using the following medications: clobazam (Onfi, Frisium), felbamate (Felbatol), vigabatrin (Sabril), or everolimus (Afinitor).
* Plan to initiate or change pharmacologic or non-pharmacologic interventions during the course of the study.
* Patient has ALT, AST, total bilirubin, or creatinine levels ≥ 2 times the ULN, alkaline phosphatase levels ≥ 3 times the ULN, or Hct \<1.2 times the LLN as determined from screening safety laboratories.
* Severe or unstable symptoms of ASD that may interfere with the study outcome evaluations and interpretation of results.
* Suffering from acute or progressive neurological disease, psychosis, schizophrenia or any psychiatric disorder or severe psychiatric abnormalities that are likely to require changes in drug therapy or interfere with the objectives of the study or the ability to adhere to protocol requirements.
* Has suspected or confirmed cardiovascular disease.
* History of treatment for, or evidence of, drug or alcohol abuse within the past year.

Primary outcomes:
measure: Aberrant Behavior Checklist- 2nd Edition (ABC-2): Irritability subscale raw score
timeFrame: Baseline to Week 12
Secondary outcomes:
measure: Aberrant Behavior Checklist- 2nd Edition (ABC-2): Lethargy/Social Withdrawal subscale
timeFrame: Baseline to Week 12
measure: Aberrant Behavior Checklist- 2nd Edition (ABC-2): Stereotypic Behavior subscale
timeFrame: Baseline to Week 12
measure: Aberrant Behavior Checklist- 2nd Edition (ABC-2): Inappropriate Speech subscale
timeFrame: Baseline to Week 12
measure: Aberrant Behavior Checklist- 2nd Edition (ABC-2): Hyperactivity/Noncompliance subscale
timeFrame: Baseline to Week 12
measure: Anxiety, Depression, and Mood Scale (ADAMS): Total Score
timeFrame: Baseline to Week 12
measure: Anxiety, Depression, and Mood Scale (ADAMS): General Anxiety subscale
timeFrame: Baseline to Week 12
measure: Anxiety, Depression, and Mood Scale (ADAMS): Social Avoidance subscale
timeFrame: Baseline to Week 12
measure: Social Responsiveness Scale - 2nd Edition (SRS-2): total T-score
timeFrame: Baseline to Week 12
measure: Ohio Autism Clinical Impressions Scale - Severity (OACIS-S) scale
timeFrame: Baseline to Week 12
measure: Ohio Autism Clinical Impressions Scale - Improvement (OACIS-I) scale
timeFrame: Baseline to Week 12
measure: Autism Screening Instrument for Educational Planning - 3rd Edition (ASIEP - 3): Interaction Assessment Autism Interaction Score
timeFrame: Baseline to Week 12
measure: Repetitive Behavior Scale - Revised (RBS-R)
timeFrame: Baseline to Week 12
measure: Brief Rating Inventory of Executive Functioning - 2nd edition (BRIEF-2): Global Executive Functioning Score
timeFrame: Baseline to Week 12
measure: Brief Rating Inventory of Executive Functioning - 2nd edition (BRIEF-2): ADHD score
timeFrame: Baseline to Week 12
measure: Brief Rating Inventory of Executive Functioning - 2nd edition (BRIEF-2): Index scores
timeFrame: Baseline to Week 12
measure: Sleep Clinical Global Impressions - Severity Scale (Sleep CGI-S)
timeFrame: Baseline to Week 12
measure: Sleep Clinical Global Impressions - Improvement Scale (Sleep CGI-I)
timeFrame: Baseline to Week 12
measure: Autism Family Experience Questionnaire (AFEQ)
timeFrame: Baseline to Week 12
measure: NIH Toolbox Scales: Satisfaction with Social Roles and Activities - Short Form 4a
timeFrame: Baseline to Week 12
measure: NIH Toolbox Scales: Life Satisfaction - Short Form 8b
timeFrame: Baseline to Week 12
measure: NIH Toolbox Scales: Positive Affect - Short Form 4a
timeFrame: Baseline to Week 12
measure: Pediatric Quality of Life Inventory (PedsQL) - Core Scale
timeFrame: Baseline to Week 12
measure: Pediatric Quality of Life Inventory (PedsQL) - Cognitive Functioning Scale
timeFrame: Baseline to Week 12
Other outcomes:
measure: AutismEyes Eyetracking system Autism Symptoms Index (ASI)
timeFrame: Baseline to Week 12
measure: Telehealth Functional Behavior Analysis (Tele-FBA)
timeFrame: Baseline to Week 12
measure: Autism Screening Instrument for Educational Planning- 3rd Edition Sample of Vocal Behavior (ASIEP-3 SVB) Vocalization Score
timeFrame: Baseline to Week 12
measure: Parent/Caregiver Improvement Scale
timeFrame: Baseline to Week 12
Locations:
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
Study officials:
References: