Clinical trial NCT02996669: Autism Biomarker Consortium for Clinical Trials
Official title: Autism Biomarker Consortium for Clinical Trials
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Autism Spectrum Disorder
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: Boston Children's Hospital
name: Duke University
name: University of California, Los Angeles
name: University of Washington
name: Food and Drug Administration (FDA)
name: National Institute of Mental Health (NIMH)
First posted: 2016-12-19
Enrollment: 399
Sex: ALL
Minimum age (years): 6
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 200 children with an autism spectrum disorder between 6-11 years old, and 75 typically developing children

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.

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 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.

Primary outcomes:
measure: NEPSY-II
timeFrame: Baseline
measure: NEPSY-II
timeFrame: 6 weeks
measure: NEPSY-II
timeFrame: 24 weeks
measure: Video Tracking
timeFrame: Baseline
measure: Video Tracking
timeFrame: 6 weeks
measure: Video Tracking
timeFrame: 24 weeks
Secondary outcomes:
measure: Aberrant Behavior Checklist (ABC)
timeFrame: Baseline, 6 weeks and 24 weeks
measure: Autism Impact Measure (AIM) Frequency
timeFrame: Baseline, 6 weeks and 24 weeks
measure: Autism Impact Measure (AIM) Impact
timeFrame: Baseline, 6 weeks and 24 weeks
measure: Child and Adolescent Symptom Inventory 5 (CASI-5)
timeFrame: Baseline, 6 weeks and 24 weeks
measure: PDD Behavior Inventory (PDD-BI)
timeFrame: Baseline, 6 weeks and 24 weeks
measure: Social Responsiveness Scale 2 (SRS-2) Total Score
timeFrame: Baseline, 6 weeks and 24 weeks
measure: Cognitive Assessment
timeFrame: Baseline and 24 weeks
measure: Resting State EEG
timeFrame: Baseline, 6 weeks and 24 weeks
measure: Faces EEG
timeFrame: Baseline, 6 weeks and 24 weeks
measure: Visual Evoked Potentials (VEPs) EEG
timeFrame: Baseline, 6 weeks and 24 weeks
measure: Biological Motion EEG
timeFrame: Baseline, 6 weeks and 24 weeks
measure: Eye-tracking (ET) Biological Motion Task
timeFrame: Baseline, 6 weeks and 24 weeks
measure: Eye-tracking (ET) Activity Monitoring Task
timeFrame: Baseline, 6 weeks and 24 weeks
measure: Eye-tracking (ET) Interactive Social Task (IST)
timeFrame: Baseline, 6 weeks and 24 weeks
measure: Eye-tracking (ET) Pupillary Light Reflex Task
timeFrame: Baseline, 6 weeks and 24 weeks
measure: Eye-tracking (ET) Visual Search/Static Social Scenes Task
timeFrame: Baseline, 6 weeks and 24 weeks
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University Child Study Center
state: Connecticut
Study officials:
affiliation: Yale University Child Study Center
name: James McPartland, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Shic F, Naples AJ, Barney EC, Chang SA, Li B, McAllister T, Kim M, Dommer KJ, Hasselmo S, Atyabi A, Wang Q, Helleman G, Levin AR, Seow H, Bernier R, Charwaska K, Dawson G, Dziura J, Faja S, Jeste SS, Johnson SP, Murias M, Nelson CA, Sabatos-DeVito M, Senturk D, Sugar CA, Webb SJ, McPartland JC. The autism biomarkers consortium for clinical trials: evaluation of a battery of candidate eye-tracking biomarkers for use in autism clinical trials. Mol Autism. 2022 Mar 21;13(1):15. doi: 10.1186/s13229-021-00482-2.