Autism Biomarker Consortium for Clinical Trials
Overview
- Phase
- N/A
- Intervention
- Not specified
- Conditions
- Autism Spectrum Disorder
- Sponsor
- Yale University
- Enrollment
- 399
- Locations
- 1
- Primary Endpoint
- NEPSY-II
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
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 T1D
- •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.)
Outcomes
Primary Outcomes
NEPSY-II
Time Frame: 24 weeks
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.
Video Tracking
Time Frame: 24 weeks
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.
Secondary Outcomes
- Autism Impact Measure (AIM) Impact(Baseline, 6 weeks and 24 weeks)
- Child and Adolescent Symptom Inventory 5 (CASI-5)(Baseline, 6 weeks and 24 weeks)
- PDD Behavior Inventory (PDD-BI)(Baseline, 6 weeks and 24 weeks)
- Aberrant Behavior Checklist (ABC)(Baseline, 6 weeks and 24 weeks)
- Autism Impact Measure (AIM) Frequency(Baseline, 6 weeks and 24 weeks)
- Social Responsiveness Scale 2 (SRS-2) Total Score(Baseline, 6 weeks and 24 weeks)
- Cognitive Assessment(Baseline and 24 weeks)
- Resting State EEG(Baseline, 6 weeks and 24 weeks)
- Faces EEG(Baseline, 6 weeks and 24 weeks)
- Visual Evoked Potentials (VEPs) EEG(Baseline, 6 weeks and 24 weeks)
- Biological Motion EEG(Baseline, 6 weeks and 24 weeks)
- Eye-tracking (ET) Biological Motion Task(Baseline, 6 weeks and 24 weeks)
- Eye-tracking (ET) Activity Monitoring Task(Baseline, 6 weeks and 24 weeks)
- Eye-tracking (ET) Interactive Social Task (IST)(Baseline, 6 weeks and 24 weeks)
- Eye-tracking (ET) Pupillary Light Reflex Task(Baseline, 6 weeks and 24 weeks)
- Eye-tracking (ET) Visual Search/Static Social Scenes Task(Baseline, 6 weeks and 24 weeks)