Autism Biomarker Consortium for Clinical Trials

Yale University399 enrolled

Overview

This is a multicenter longitudinal study that aims to identify, develop and validate a set of measures that can be used as stratification biomarkers and/or sensitive and reliable objective measures of social impairment in autism spectrum disorders (ASD) that could serve as markers of long term clinical outcome. The main study will include 275 individuals: 200 ASD subjects between 6-11 years old, and 75 TD subjects roughly matched by age and sex to the ASD group.

The specified aims of this study are to accelerate the development of effective treatments for social impairment in ASD by validating outcome measures that will be sensitive and reliable assessments of response to treatment and electroencephalography (EEG) and eye-tracking (ET) biomarkers. These hypothesized outcomes could then be used to reduce the heterogeneity of samples via stratification, could possibly indicate early efficacy, and/or demonstrate target engagement. The consortium will conduct a naturalistic, longitudinal study of preschool and school-aged (6-11 years) children with ASD and typical development (TD) with intelligence quotient(s) (IQ) ranging from 50-150. Children will be assessed across three time points (Baseline, 6 weeks and 24 weeks) using clinician, caregiver and lab-based (LB) measures of social impairment, along with a battery of conceptually related EEG and ET tasks and independent ratings of clinical status.

Study Type

OBSERVATIONAL

Enrollment

399

Conditions

Autism Spectrum Disorder

Eligibility

Sex: ALLMin age: 6 YearsMax age: 11 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: For All Subjects: * Males and Females Age 6 - 11 (\<11:5 at timepoint #1 unless all study procedures will be completed before the participant turns 12.0 and prior approval by the Principal Investigator is obtained). * Written parental consent obtained prior to any study procedures. * Participant and parent/guardian must be English speaking. For TD Participants: • IQ 80-150 as assessed by the Differential Ability Scales (DAS)- 2nd Edition For ASD Participants: * Diagnosis of ASD based on Diagnostic and Statistical Manual of Mental Disorders (DSM-5), the Autism Diagnostic Observation Schedule (ADOS-2), and the Autism Diagnostic Interview-Revised, short form (ADI-R). Diagnostic evaluations will be completed by research staff and supervised by a licensed psychologist. * IQ 60-150 as assessed by the Differential Ability Scales (DAS)- 2nd Edition * If parents are biological, a minimum of the child and one parent (if accompanying the child at study visits) will be required to participate in the blood draw procedure. It is preferred that the child and both biological parents participate in the blood draw procedure, but the inability to obtain blood samples from trios will not be exclusionary. Exclusion Criteria: For All Subjects: * Known genetic or neurological syndrome with established link to autism (in addition to ASD for ASD participants), but not events in which the link to ASD is less well known/established (e.g., 16p11.2 CNVs, CHD8 mutations, Trisomy 21, 22q deletion syndrome) * History of epilepsy or seizure disorder (except for history of simple febrile seizures or if the child is seizure free (regardless of seizure type) for the past year). * Motor or sensory impairment that would interfere with the valid completion of study measures including significant hearing or vision impairment not correctable by a hearing aid or glasses/contact lenses. Children who wear bifocal or progressive lenses are not eligible. * Medication is not exclusionary. Children taking neurological or psychiatric medications, including anti epileptics and psychopharmacological agents, must be stable on the medication and dose for 8 weeks prior to T1D1. * History of significant prenatal/perinatal/birth injury (birth \<36 weeks AND weight \<2000 grams (approximately 4.5lbs)). * History of neonatal brain damage. (e.g., with diagnoses hypoxic or ischemic event) * Any other factor that the investigator feels would make assessment or measurement performance invalid. For ASD Participants: • Any known environmental circumstances that is likely to account for the picture of autism in the proband (severe nutritional or psychological deprivation etc.) For TDs Participants: * Known historical diagnosis of ASD or a sibling with ASD. * Active psychiatric disorder (depression, anxiety, ADHD, etc.) and/or any current treatment (medication or other treatment) for a psychiatric condition. Participants will be screened using the Child/Adolescent Symptom Inventory (CASI-5). Due to the measurements sensitivity, any score in the clinical range will be reviewed by research staff for determination of eligibility.

Locations (1)

Yale University Child Study Center

New Haven, Connecticut, United States

Outcomes

Primary Outcomes

NEPSY-II

NEPSY-II - Memory for Faces Subtest (administered to all ages): The NEPSY-II Memory for Faces subtest entails viewing a series of faces and having the child identify the sex of each face. The child is then shown three faces at a time and required to identify the previously seen face.

Time frame: Baseline

NEPSY-II

Time frame: 6 weeks

NEPSY-II

Time frame: 24 weeks

Video Tracking

Video tracking of social behavior is an observational method involving automated tracking of children's movements using the Noldus EthoVision Computerized tracking system. Using computer vision, video recordings of children's movements assess proximity-seeking/approach behaviors. During one six-minute free-play session in the laboratory, children's movements will be recorded from a ceiling-mounted camera and two side cameras while a parent sits in a corner of the room. Software automatically tracks the child (via the ceiling mounted camera) as the child plays with a standardized set of toys and interacts with the parent, and computes the percentage of session spent near the parentlatency to approach the parent, percentage of time spent in the periphery and latency to approach the periphery. A subset of side camera recordings will be manually coded by reliable coders for social engagement behaviors to validate the automatically generated movement behaviors calculated by EthoVision.

Time frame: Baseline

Video Tracking

Data from ClinicalTrials.gov

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Secondary Outcomes

Aberrant Behavior Checklist (ABC)

The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors of children and adults with neurodevelopmetnal disorder at home, in residential facilities, ICFs/MR, and work training centers. It is also useful for classifying problem behaviors of children and adolescents with neurodevelopmetnal disorder in educational settings, residential and community-based facilities, and developmental centers. Aman MG, Singh NN, Stewart AW, Field CJ. The aberrant behavior checklist: a behavior rating scale for the assessment of treatment effects. Am J Ment Defic. 1985; 89(5):485-491.