Clinical trial NCT03900923: Cannabidiol for ASD Open Trial
Official title: A Phase 2 Study of Cannabidiol as a New Treatment for Autism Spectrum Disorder in Children and Adolescents
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: ASD
Autism Spectrum Disorder
Keywords: cannabidiol (CBD)
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
First posted: 2019-04-03
Enrollment: 29
Sex: ALL
Minimum age (years): 7
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Clinical Global Impression Scale-Improvement (CGI-I)
timeFrame: Week 6
Secondary outcomes:
measure: Change in Repetitive Behavior Scale-Revised (RBS-R) Score
timeFrame: Baseline, Week 6
measure: Change in Social Responsiveness Scale, 2nd Edition (SRS-2), School-Age Form Score
timeFrame: Baseline, Week 6
measure: Change in Aberrant Behavior Checklist (ABC) - Irritability Subscale Score
timeFrame: Baseline, Week 6
measure: Change in Screen for Child Anxiety Related Disorders (SCARED), Parent Version Score
timeFrame: Baseline, Week 6
measure: Change in Sleep Disturbance Scale for Children (SDSC) Score
timeFrame: Baseline, Week 6
measure: Change in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Parent/Caregiver Form Score
timeFrame: Baseline, Week 6
measure: Change in Clinical Global Impression-Severity (CGI-S) Score
timeFrame: Baseline, Week 6
measure: Change in Autism Family Experience Questionnaire (AFEQ) Score
timeFrame: Baseline, Week 6
measure: Change in Anxiety Scale for Children - Autism Spectrum Disorder - Parent Versions (ASC-ASD-P) Score
timeFrame: Baseline, Week 6
measure: Anxiety Scale for Children - Autism Spectrum Disorder (ASC-ASD-C) - Child Version
timeFrame: Baseline, Week 6
measure: Change in Ohio State University (OSU) Autism Clinical Global Impressions: Severity
timeFrame: Baseline, Week 6
measure: OSU Autism Clinical Global Impressions: Improvement
timeFrame: Week 6
measure: Change in Behavioral Inflexibility Scale (BIS) Score
timeFrame: Baseline, Week 6
measure: Change in Home Situations Questionnaire - Modified for ASD (HSQ-ASD) Score
timeFrame: Baseline, Week 6
measure: Change in Strengths and Weaknesses of Attention-Deficit/Hyperactivity Disorder Symptoms and Normal Behavior (SWAN) Score
timeFrame: Baseline, Week 6
Other outcomes:
Locations:
city: New York
country: United States
facility: NYU Langone Health
state: New York
Study officials:
affiliation: New York Langone Health
name: Francisco X Castellanos, MD
role: PRINCIPAL_INVESTIGATOR
References: