Trial Outcomes & Findings for Low-Dose Ketamine in Children With ADNP Syndrome (NCT NCT04388774)

Ten participants were screened, and all met criteria for inclusion and were enrolled between August 2020 and May 2021.

Low-Dose Ketamine in Children With ADNP Syndrome

Number of Participants with an adverse event as defined by the Systematic Longitudinal Assessment of Adverse Events (SLAES) which is a comprehensive form that assesses medical and behavioral conditions that were present at screening and/or baseline. Conditions are considered treatment emergent if their severity increased significantly after the participant had taken at least one dose of the study treatment. Treatment emergent adverse events will be tracked considered in the adverse event safety analysis. Severity of adverse events are categorized as mild, moderate, severe, life-threatening, or resulting in death and the treating physician indicates if the adverse event was related or unrelated to study drug.

Changes in scale at week 1 compared to baseline. Aberrant Behavior Checklist is a behavior rating scale for the assessment of treatment effects. Each item is scored as 0 (never a problem), 1 (slight problem), 2 (moderately serious problem), or 3 (severe problem). Subscales from 0-45 for Irritability; 0-48 for Social Withdrawal and Hyperactivity; from 0-21 for Stereotypy; and 0-12 for In Speech , with total scale from 0 to 48, with higher score indicating worse health outcomes.

The ADAMS is a parent/caregiver-completed measure and consists of 28 items, grouped into five subscales (Manic/Hyperactive Behavior, Depressed Mood, Social Avoidance, General Anxiety, Obsessive Behavior), and scored on a four-point Likert scale that combines frequency and severity ratings from 0-3. Subscales range - Hyperactivity 0-15; Depressed 0-21; Social Avoidance 0-21; General anxiety 0-21; OCD 0-9. Scores are not summed. Higher score indicates poorer health outcomes.

Change in repetitive behaviors at weeks 1 compared to baseline. RBS-R subscales - Stereo 0-18; Self injury 0-24; Compulsive 0-24; Ritualistic 0-18; Sameness 0-33; Restricted 0-12. Total scale range from 0 to 126 with higher score indicating worse health outcomes.

Changes in scale at weeks 2, and 4 compared to baseline. Clinical Global impressions - Improvement Scale is anchored to symptoms of ADNP syndrome for the assessment of treatment effects. CGI-I total score from 1 to 7 point scale, with higher score indicating worse health outcomes.

Change in sleep habits at week 1 compared to baseline. Full scale from 0 to 110, with higher score indicating worse health outcomes.

Expressive and receptive language assessed by Peabody Picture Vocabulary Test and Expressive Vocabulary Test at Day 1, Weeks 1, 2, and 4. Full scale from 40 to 160, with higher score indicating better health outcomes.

Change at Day 1 and Week 1 as compared to baseline using computerized eye tracking to record where the subject is looking during an activity in which the subject will see a video of a person with two objects, turning her head towards one of the objects, the target. Mean proportion of trials in which participants made saccades to the target before the distractor.

Change at week 1, week 2, and week 4 as compared to baseline using computerized eye tracking to record where the subject is looking during an activity in which the subject will see different social and non-social stimuli. Latency to first saccade to the target

Change at Day 1 and Week 1 as compared to baseline using computerized eye tracking to record where the subject is looking during an activity in which the subject will see different social and non-social stimuli. Proportion of time participants spent dwelling on the target versus distractor.

Electroencephalographic recordings to measure Auditory Event Related Potentials at baseline, week 1, week 2, and week 4. In separate blocks, participants heard a 500-ms click at either a stimulation rate of 40 or 20 Hz. Click trains were presented 150 times each, with an intertrial interval of 50 ms, at approximately 60 db. Higher number indicates higher amplitude neural response to auditory stimuli.

Changes in scale at week 4 compared to baseline. Vineland Adaptive Behavior Scales measures adaptive functioning. Higher score indicating better health outcomes. Domain scores are standard scores - population mean 100 standard deviation 15. an overall composite score, it consists of three subscales: (a) communication (receptive, expressive, written), (b) socialization (interpersonal relationships, play and leisure, coping skills), and (c) daily living (person, domestic, community).

Caregiver Strain Questionnaire (CGSQ) is a 13 question tool, with a 5-point Likert scale ranging from Not at all (0) to Very much (4). Domains (Objective strain, Subjective externalized strain, Subjective internalized strain) are averaged scores, range from 0-4. Total score (Global score) is a sum of the three subdomains. Full scale range 0-12, higher score indicates more severe strain.