Cannabidiol for ASD Open Trial

• ClinicalTrials.gov Identifier: NCT03900923
• Recruitment Status: Active, not recruiting
• First Posted: April 3, 2019
• Last Update Posted: May 6, 2023
• Sponsor: NYU Langone Health
• Information provided by (Responsible Party): NYU Langone Health

Study Description

Brief Summary:

This is a 6-week open trial to identify the optimal dosing of cannabidiol (CBD) in youth with autism spectrum disorder (ASD) and to identify primary and secondary outcomes for future controlled studies. This study evaluates change in symptoms commonly associated with ASD, as evidence suggests that CBD may be effective in addressing difficulties such as irritability and anxiety, while maintaining a benign adverse effect (AE) profile in children and adolescents.

30 male and female participants with ASD between the ages of 7 and 17 years old are being recruited. Participants have fluent speech and an estimated IQ greater than or equal to 80. Study intervention is 98% pure CBD. The CBD is Greenwich Biosciences, Inc.'s 100mg/mL oral solution, brand name EPIDIOLEX. First, a Bayesian optimal interval (BOIN) design was used, such that participants were assigned to cohorts of size 3 receiving doses of 3, 6, or 9 mg/kg/day, depending on the treatment response of participants in prior cohorts.

The BOIN design ended after the fifth cohort of participants, and the two lower doses, 3 and 6 mg/kg/day, were eliminated. The highest dose, 9 mg/kg/day, was not tested. Therefore, in subsequent cohorts, we will be examining 9 mg/kg/day exclusively in up to 15 additional participants with co-occurring ASD and attention-deficit/hyperactivity disorder (ADHD) diagnoses, as this clinical profile appears to most closely resemble youth classified as responders within the BOIN design.

Condition or disease	Intervention/treatment	Phase
ASD; Autism Spectrum Disorder	Drug: 98% pure CBD	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of Cannabidiol as a New Treatment for Autism Spectrum Disorder in Children and Adolescents
• Actual Study Start Date: March 12, 2019
• Estimated Primary Completion Date: May 16, 2023
• Estimated Study Completion Date: May 4, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: 98% pure CBD; 98% pure CBD. The CBD will be 100mg/mL oral solution provided by Greenwich Biosciences, Inc.	Drug: 98% pure CBD; A Bayesian optimal interval (BOIN) design was used, such that participants were assigned to cohorts of size 3 receiving doses of 3, 6, or 9 mg/kg/day, depending on the treatment response of participants in prior cohorts. The BOIN design has ended, and two doses have been tested and eliminated (3 and 6 mg/kg/day). We are now examining 9 mg/kg/day exclusively.

Outcome Measures

Primary Outcome Measures :

1. Clinical Global Impression Scale -Improvement (CGI-I) [ Time Frame: 6 Weeks ]
   This is a 7-point scale measuring symptom change from baseline.

Secondary Outcome Measures :

1. Repetitive Behavior Scale-Revised (RBS-R) [ Time Frame: Baseline, Week 6 ]
   The RBS-R consists of six subscales covering a range of RRB subtypes including: Stereotyped Behavior, Self-injurious Behavior, Compulsive Behavior, Routine Behavior, Sameness Behavior, and Restricted Behavior. The presence and frequency of behaviors are rated on a 4-point scale (ranging from 0=behavior does not occur to 3=behavior occurs and is a severe problem).
2. Social Responsiveness Scale, 2nd Edition (SRS-2), School-Age Form [ Time Frame: Baseline, Week 6 ]
   Five domains are assessed including: Social Awareness, Social Cognition, Social Communication, Social Motivation, and Restricted Interests and Repetitive Behavior. Items are scored on a 4-point scale (ranging from 1=not true to 4=almost always true).
3. Aberrant Behavior Checklist (ABC) - Irritability and Social Withdrawal Subscales [ Time Frame: Baseline, Week 6 ]
   The subscales of the ABC include: Irritability, Social Withdrawal, Stereotypic Behavior, Hyperactivity/Noncompliance, and Inappropriate Speech. Items are rated on a 4-point scale (ranging from 0=no problem at all to 3 = problem is severe in degree).
4. Anxiety, Depression and Mood Scale (ADAMS) [ Time Frame: Baseline, Week 6 ]
   28 symptom items that resolve into five subscales labeled: Manic/Hyperactive Behavior, Depressed Mood, Social Avoidance, General Anxiety, and Compulsive Behavior. Items are rated on 4-point scale ranging from 0=not a problem to 3=severe problem.
5. Screen for Child Anxiety Related Disorders (SCARED), Parent Version [ Time Frame: Baseline, Week 6 ]
   The SCARED, Parent Version is a parent report measure developed to measure child anxiety symptoms. Subscales include Somatic Symptoms/Panic Disorder, Generalized Anxiety Disorder, Separation Anxiety, Social Phobia, and School Phobia. Items are rated on a 3-point scale ranging from 0=not true or hardly ever true to 2=very true or often true.
6. Sleep Disturbance Scale for Children (SDSC) [ Time Frame: Baseline, Week 6 ]
   Six subscales including Disorders of Initiating and Maintaining Sleep, Sleep Breathing Disorders, Disorders of Arousal, Sleep Wake Transition Disorders, Disorders of Excessive Somnolence, and Sleep Hyperhydrosis. Items are rated on 5-point scale where 1=never and 5=always (daily). Subscale scores sum to equal a total score
7. Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Parent/Caregiver Form [ Time Frame: Baseline, Week 6 ]
   Used to measure adaptive functioning across three core domains (Communication, Daily Living Skills, and Socialization), and two optional domains (Motor Skills and Maladaptive Behavior); items are rated on a 3-point scale (0=never; 1=sometimes; 2=usually or often). The core domains sum to a total Adaptive Behavior Composite.
8. Clinical Global Impression-Severity (CGI-S): [ Time Frame: Screening, Baseline, Week 6 ]
   Reflects clinicians impression of severity of illness on a 7-point scale ranging from 1=not at all to 7=among the most extremely ill.
9. Autism Family Experience Questionnaire (AFEQ) [ Time Frame: Baseline, Week 6 ]
   Parent/Caregiver form used to measure impact of autism interventions on family experience and quality of life. Items are rated on a 5-point scale where 1=always and 5=never.
10. Anxiety Scale for Children - Autism Spectrum Disorder - Parent Versions (ASC-ASD-P) [ Time Frame: Baseline, Week 6 ]
    Parent/Caregiver form developed to detect symptoms of anxiety in youth with ASD. Composed of four subscales (Performance Anxiety, Uncertainty, Anxious Arousal, and Separation Anxiety), items are rated on a 4-point scale (0=never and 3=always). Subscales sum to equal a total score.
11. Anxiety Scale for Children - Autism Spectrum Disorder (ASC-ASD-C) - Child Versions [ Time Frame: Baseline, Week 6 ]
    Child form developed to detect symptoms of anxiety in youth with ASD. Composed of four subscales (Performance Anxiety, Uncertainty, Anxious Arousal, and Separation Anxiety), items are rated on a 4-point scale (0=never and 3=always). Subscales sum to equal a total score.
12. OSU Autism Clinical Global Impressions: Severity [ Time Frame: Screening, Baseline, Week 6 ]
    Reflects clinicians impression of severity of illness on a 7-point scale ranging from 1=not present to 7="classic" autism.
13. OSU Autism Clinical Global Impressions: Improvement [ Time Frame: Week 6 ]
    Reflects clinicians impression of improvement on a 7-point scale ranging from 1=very much improved to 7=very much worse.
14. Behavioral Inflexibility Scale (BIS) [ Time Frame: Baseline, Week 6 ]
    Parent/Caregiver measure designed to assess rigid patterns of behavior commonly associated with ASD. The measure is composed of 38 items rated on a 6-point Likert scale where 0=Not at all a problem and 5=Very severe or extreme problem. Items sum to a total score.
15. Home Situations Questionnaire - Modified for ASD (HSQ-ASD) [ Time Frame: Baseline, Week 6 ]
    Parent/Caregiver questionnaire that measures behavioral noncompliance in everyday settings. Consists of two 12-item factors: Socially Inflexible and Demand Specific. Severity of non-compliance is rated on a 1-9 Likert scale, and higher scores indicate greater non-compliance.
16. 16. Strengths and Weaknesses of Attention-Deficit/Hyperactivity Disorder Symptoms and Normal Behavior (SWAN) [ Time Frame: Baseline, Week 6 ]
    Parent/Caregiver measure designed to assess symptoms of ADHD in children and adolescents. Includes 18 items rated on a 7-point Likert scale ranging from far-below average to far-above average. Subscales include ADHD-Inattentive and ADHD-Hyperactive/Impulsive. Total range of score is 0-126; higher score indicates greater symptoms.

Eligibility Criteria

• Ages Eligible for Study: 7 Years to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Male or female pediatric outpatients aged between and including 7 to 17.9 years old
• Diagnosis of ASD confirmed by the ADOS-2 and DSM-5 criteria
• Diagnosis of ADHD confirmed by clinician review of K-SADS-COMP and DSM-5 Criteria
• SRS-2 Total T-score of 66 or higher
• CGI-S score of 4 or higher
• Physical exam and laboratory results that are within normal range for their age
• Fluent speech
• Estimated IQ of at least 80
• Presence of a parent/legal guardian who is able to consent for their participation and complete assessments regarding the child's development and behavior throughout the study

Exclusion Criteria:

• History or current evidence of significantly impaired liver function, defined as 1) Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 5 × upper limit of normal (ULN); 2) ALT or AST > 3 × ULN with concomitant total bilirubin > 2.0 × ULN; or 3) ALT or AST ≥ 3 × ULN with the appearance of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, and/or eosinophilia
• History of active seizure disorder or epilepsy; patients seizure free for >5 years off of antiepileptic drugs and other than uncomplicated febrile seizures are not excluded
• Exposure to any investigational agent in the 30 days prior to initiation of trial
• Treatment with CBD or other cannabinoid within the previous two months
• Current use of medications metabolized primarily by CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP3A4, or CYP2D6 isoenzymes. Methylphenidate is not contraindicated.
• History of drug abuse including marijuana/cannabis use in the past 3 months
• Positive urine sample results from drug screening indicating presence of the following drugs: THC, opiates, methamphetamine, or cocaine
• Diagnosis of a known genetic disorder (e.g., Prader-Willi Syndrome, Angelman Syndrome, etc.).
• Active suicidality (ideation and plan) is present
• A current psychiatric diagnosis of bipolar disorder, major depressive disorder (MDD), psychosis, schizophrenia, or post-traumatic stress disorder (PTSD)
• Pregnant or lactating patients or patients who will not agree to be abstinent or use contraception
• A medical condition that severely impacts the subject's ability to participate in the study, interferes with the conduct of the study, confounds interpretation of study results or endangers the subject's well-being
• Diagnosis of Rett Syndrome or Childhood Disintegrative Disorder or marked sensory impairment such as deafness or blindness
• Subjects who have had changes in allied health therapies, behavioral or educational interventions within 4 weeks prior to initiation of trial, other than those associated with school holidays
• Subjects who have had changes in non-exclusionary psychotropic medications within 4 weeks of initiation of trial

Contacts and Locations

Locations

United States, New York

NYU Langone Health

New York, New York, United States, 10016

Sponsors and Collaborators

NYU Langone Health

Investigators

• Principal Investigator: Francisco X Castellanos, MD; New York Langone Health

More Information

• Responsible Party: NYU Langone Health
• ClinicalTrials.gov Identifier: NCT03900923
• Other Study ID Numbers: 18-00250
• First Posted: April 3, 2019
• Last Update Posted: May 6, 2023
• Last Verified: May 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
• Supporting Materials: Study Protocol; Informed Consent Form (ICF)
• Time Frame: Proposals may be submitted up to 36 months following article publication. After 36 months the data will be available in the investigator's University's data warehouse but without investigator support other than deposited metadata. Information regarding submitting requests and accessing data may be found at (Link to be provided).
• Access Criteria: Data will be available for any purpose.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by NYU Langone Health:

cannabidiol (CBD)

Additional relevant MeSH terms:

Autism Spectrum Disorder; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders