Cannabidivarin (CBDV) vs. Placebo in Children With Autism Spectrum Disorder (ASD)

Change in repetitive behavior from baseline will be assessed using the RBS-R, a 43-item self-report instrument that is used to measure the breadth of repetitive behaviors specific to autism spectrum disorder (ASD) symptomatology. The 43 items encompass 6 behavioral subscales including: Stereotypic (6 items); Self-injurious (8 items); Compulsive (8 items); Ritualistic (6 items); Sameness (11 items); and Restricted Behavior (4 items). A list of behaviors will be presented and the parent will be asked to choose a score that best describes how much of a problem the behavior has been over the last month. Behaviors are rated on a 4-point scale: 0 (behavior does not occur), 1 (behavior occurs and is a mild problem), 2 (behavior occurs and is a moderate problem) and 3 (behavior occurs and is a severe problem). Higher scores reflect increased severity of repetitive behavior for that scale. Scores for each of the 6 subscales will be summarized by arm using basic descriptive statistics.

Change in rigidity from baseline will be assessed using the MERS-R. MERS-R is designed to assess three domains of rigid behavior in children (and adults) with ASD: Behavioral Rigidity (e.g., insistence on sameness, things must be done his/her way, etc.); Cognitive Rigidity (e.g., special interests, inflexible adherence to rules, etc.); and Protest (in response to deviation from rigidity; e.g., verbal objection, tantrum, physical aggression). MERS-R is a clinician-rated scale and will only be completed only for subjects who display rigid behaviors at baseline, and study visits during week 4, week 8, and week 12. The MERS-R consists of 43 items. Each item is scored based on a 4-point scale ranging from 0 (no problem) to 3 (severe problem) for rigid behaviors displayed over the past month, yielding an overall MERS-R score of 0-129. Higher scores are associated with more severe rigidity. Scores will be summarized by study arm using basic descriptive statistics.

Change in aberrant behavior from baseline will also be evaluated using the Social Withdrawal subscale of the Aberrant Behavior Checklist (ABC). The ABC is an informant rating instrument that measures behavior in individuals with developmental disability and ASD. The ABC-SW scale measures behavior using a 4-point severity scale, ranging from 0-3, where parents rate aberrant behaviors as 0 = no problem at all, 1 = behavior is a problem but in a slight degree, 2 = problem is moderately serious, and 3 = problem is severe in degree, such that higher scores are associated with increased severity of social withdrawal, for an overall possible score of 0-48. Scores will be summarized by study arm using basic descriptive statistics.

Change in quality of life is assessed using the PedsQL family impact module, a 36-item self-report caregiver form used to measure caregiver functioning. PedsQL encompasses 6 scales: Physical Functioning (6 items), Emotional Functioning (5 items), Social Functioning (4 items), Cognitive Functioning (5 items), Communication (3 items), Worry (5 items) and 2 scales measuring caregiver-reported family functioning: Daily Activities (3 items) and Family Relationships (5 items). Each item is scored using a 5-point scale ranging from 0 (never a problem) to 4 (always a problem). Items are then reverse-scored and transformed to a 0-100 scale (0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0), such that higher scores indicate better functioning (less negative impact). Scale Scores are computed as the sum of the items divided by the number of items answered (to account for missing data). If >50% of the items in the scale are missing, a scale score is not computed. Scores will be summarized by study arm.

Change in adaptive behavior from baseline will be assessed using the VABS-3. The VABS-3 is an instrument that measures adaptive behavior across 5 domains: communication, daily living skills, socialization, motor skills, and maladaptive behavior of individuals with developmental disabilities. The Survey Interview Form (semi-structured interview) will be administered to a participant's reliable caregiver in this study, during which the interviewer will ask the caregiver open ended questions relating to the subject's activities and behavior. Scoring involves assigning points (0, 1, or 2) to each item based on the responses to the questions. These scores are then compared to normative data to determine the individual's standing relative to peers. Higher scores are generally indicative of better adaptive behavior. Scores will be summarized by study arm using basic descriptive statistics.

The degree of change of in condition from baseline will be assessed using the CGI-I scale. The CGI-I is a clinician-rated global measure of improvement scale used to assess the degree of symptom change in a patient relative to baseline condition. It consists of a 7-point scale as follows: 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse, such that lower scores are indicative of increased symptom improvement. Scores will be summarized by study arm using basic descriptive statistics.