Clinical trial NCT05294705: The Autism Biomarkers Consortium for Clinical Trials: Confirmation Study
Official title: The Autism Biomarkers Consortium for Clinical Trials
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Autism Spectrum Disorder
Keywords: Biomarkers
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: Boston Children's Hospital
name: Duke University
name: Children's Hospital Los Angeles
name: University of Washington
name: Food and Drug Administration (FDA)
name: University of Alabama at Birmingham
name: University of California, Los Angeles
name: Seattle Children's Hospital
name: National Institutes of Health (NIH)
name: National Institute of Mental Health (NIMH)
First posted: 2022-03-24
Enrollment: 400
Sex: ALL
Minimum age (years): 6
Maximum age (years): 11
Standard ages: CHILD
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 200 children with an autism spectrum disorder (ASD) between 6-11 years old, and 200 typically developing children between 6-11 years old

Brief summary: This is a multicenter longitudinal study that aims to validate a set of measures that were previously identified as promising candidate biomarkers and/or sensitive and reliable objective measures of social function in ASD for potential use in clinical trials. The confirmation study will repeat the data collection and analysis protocols from the original ABC-CT study. This confirmation study will recruit 200 ASD and 200 TD comparison participants who are 6-11 years old, matching the overall sample size but providing a larger normative reference sample and greater statistical power for group comparisons.

Detailed description: The goal of this consortium is to establish tools that can be used as biomarkers and/or sensitive and reliable objective assays of social function in autism spectrum disorder (ASD) clinical trials. Specifically, we aim to accelerate the development of effective treatments for social function in ASD by validating (a) outcome measures that will be sensitive and reliable assessments of response to treatment and (b) biomarkers in the domains of electroencephalography (EEG), eye-tracking (ET) and behavioral measures of social function to reduce heterogeneity of samples via stratification. The consortium will conduct a naturalistic, longitudinal study of school-aged (6-11 years) children with ASD and typical development (TD) with IQ ranging from 60-150 (ASD) and 80-150 (TD). Children will be assessed across three time points (T1: Baseline, T2: 6 weeks, T3: 24 weeks) using clinician and caregiver assessments along with a battery of conceptually related EEG and ET tasks and independent ratings of clinical status.

Eligibility criteria: Inclusion Criteria:

For All Subjects:

1. Males and Females Age 6 - 11 (less than 11 years and 6 months old at T1D1 unless all study procedures will be completed before the participant turns 12.0 and prior approval by the Principal Investigator is obtained).
2. Written parental permission, and child assents when applicable, obtained prior to any study procedures.
3. IQ 60-150 (ASD) and 80-150 (TD) as assessed by the Differential Ability Scales - 2nd Edition.
4. Participant and parent/guardian must be English speaking.

For ASD Participants (only):

1. Diagnosis of ASD based on Diagnostic and Statistical Manual of Mental Disorders (DSM-5), the Autism Diagnostic Observation Schedule (ADOS-2) or BOSA and the Autism Diagnostic Interview-Revised, short form (ADI-R). Diagnostic evaluations will be completed by research staff and supervised by a licensed psychologist.
2. If parents are biological, a minimum of the child and one parent will be required to consent to the blood draw procedure. It is preferred that the child and both biological parents participate in the blood draw procedure. The inability to obtain blood samples will not be exclusionary.

Exclusion Criteria:

For All Subjects:

1. Known genetic or neurological syndrome with an established link to autism (in addition to ASD for ASD participants)

   1. This does not include events in which the link to ASD is less well known/established (e.g., 16p11.2 CNVs, CHD8 mutations, Trisomy 21, 22q deletion syndrome, Dup 15q Syndrome).
   2. Specific cases will be discussed with the clinical team who will make a final determination, as needed.
2. History of epilepsy or seizure disorder

   a. This does not include history of simple febrile seizures or if the child is seizure free (regardless of the seizure type) for the past year.
3. 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.
4. Children who are taking neurological or psychiatric medications that are not stable on prescription or dose for 8 weeks prior to T1D1.

   a. 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.
5. History of significant prenatal/perinatal/birth injury as defined by birth \<36 weeks AND weight \<2000 grams (approximately 4.5.lbs).
6. History of neonatal brain damage. (e.g., with diagnosed hypoxic or ischemic event).
7. Any other factor that the investigator feels would make assessment or measurement performance invalid.
8. Participation in the original ABC-CT study.

For ASD Participants (only):

1. Any known environmental circumstance that is likely to account for autism in the proband.

For TD Participants (only):

1. Known historical diagnosis of ASD or a sibling with ASD.
2. Criteria score in the ASD range on the ADOS/BOSA at T1
3. Active psychiatric disorder (depression, anxiety, ADHD, etc.) and/or any current treatment (medication or other treatment) for a psychiatric condition.

   1. Participants will be screened using the Child/Adolescent Symptom Inventory (CASI- 5). Due to the instrument's high sensitivity and potential for false positives, any score in the clinical range will be reviewed by research staff for determination of eligibility.

Primary outcomes:
measure: N170 Latency to Upright Human Faces
timeFrame: Baseline
measure: Oculomotor Index of Gaze to Human Faces (OMI)
timeFrame: Baseline
measure: VABS: Vineland Adaptive Behavior Scales- III Socialization
timeFrame: Baseline
measure: N170 Latency to Upright Human Faces
timeFrame: 6 weeks
measure: Oculomotor Index of Gaze to Human Faces (OMI)
timeFrame: 6 weeks
measure: VABS: Vineland Adaptive Behavior Scales- III Socialization
timeFrame: 6 weeks
measure: N170 Latency to Upright Human Faces
timeFrame: 24 weeks
measure: Oculomotor Index of Gaze to Human Faces (OMI)
timeFrame: 24 weeks
measure: VABS: Vineland Adaptive Behavior Scales- III Socialization
timeFrame: 24 weeks
Secondary outcomes:
measure: Aberrant Behavior Checklist (ABC)
timeFrame: Baseline, 6 weeks and 24 weeks
measure: Autism Impact Measure (AIM)
timeFrame: Baseline, 6 weeks and 24 weeks
measure: Behavior Assessment System for Children -3 (BASC-3)
timeFrame: Baseline
measure: Child and Adolescent Symptom Inventory 5 (CASI-5)
timeFrame: Baseline and 24 weeks
measure: PDD Behavior Inventory (PDD-BI)
timeFrame: Baseline, 6 weeks and 24 weeks
measure: Social Responsiveness Scale 2 (SRS-2)
timeFrame: The Social Responsiveness Scale 2 (SRS-2) is completed in just 15 to 20 minutes and identifies social impairment associated with autism spectrum disorders (ASDs) and quantifies its severity.
measure: Cognitive Assessment
timeFrame: Differential Ability Scales - Second Edition; DAS-II (Elliott C, 2007): The DAS-II is a clinical instrument designed to assess cognitive ability include variables such as verbal cluster, spatial cluster, nonverbal cluster, special nonverbal composite and
measure: Resting State EEG
timeFrame: Baseline, 6 weeks and 24 weeks
measure: Faces Processing EEG
timeFrame: Faces processing is a foundation for social perception and attention and serves as a promising and robust biomarker of social impairment in ASD and a potential index of subgroup differences. As the primary non-resting paradigm, the FACES task will always
measure: Visual Evoked Potentials (VEPs) EEG
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) Static Social Scenes Task
timeFrame: Baseline, 6 weeks and 24 weeks
measure: NEPSY-II
timeFrame: Baseline, 6 weeks and 24 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: New Haven
country: United States
facility: Yale Child Study Center
state: Connecticut
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Durham
country: United States
facility: Duke
state: North Carolina
city: Seattle
country: United States
facility: Unviersity of Washington
state: Washington
Study officials:
affiliation: Yale University
name: James McPartland, PhD
role: PRINCIPAL_INVESTIGATOR
References: