Clinical trial NCT06413316: ABC-CT Pre-School Feasibility Study
Official title: Autism Biomarkers Consortium for Clinical Trials (ABC-CT) Pre-School Feasibility Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Autism Spectrum Disorder
Keywords: Biomarker
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: Duke University
name: Boston Children's Hospital
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: 2024-05-14
Enrollment: 50
Sex: ALL
Minimum age (years): 3
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: aged 3-5, with IQ ranging from 60-150, recruited from 5 clinical implementation sites in the US.

Brief summary: This is a multicenter study that aims to determine whether the EEG and ET experiments studied in the ABC-CT Phase 1 and ABC-CT Confirmation studies can be successfully used with 3-5-year-old children and to determine the viability of these measures as potential biomarkers in 3-5-year-old children with ASD. Blood (DNA) samples will be collected from participants with ASD and biological parents for future genomic analyses, and raw, processed, and analyzed data will be shared to create a community resource accessible for use by all qualified investigators. These objectives are designed to advance the long term objective of developing promising biomarkers via the FDA Biomarker Qualification Program. This feasibility study aims to enroll 25 ASD and 25 TD eligible participants who are 3-5 years old.

Detailed description: The ABC-CT Pre-School Feasibility Study will collect data in a cohort of participants to determine feasibility of the measures used in the ABC-CT Phase 1 study and ABC-CT Confirmation study in 3-5 year old participants. We will be able to examine distributional and psychometric properties of the measures in this group and obtain preliminary estimates of group differences and associations with clinical measures. In addition, we aim to determine the viability of EEG and ET measures as potential biomarkers in 3-5-year-old children with ASD. Viability will be evaluated in terms of (a) valid data acquisition, including adequate levels of participant compliance, (b) reliability of data collection across sites, (c) construct validity in relation to social function, and (d) distributional/psychometric properties.

Primary Objectives:

1. To evaluate the feasibility of collecting EEG and ET assessments used in the Phase 1 and Confirmation studies in 3-5 year old.
2. To determine the viability of adapted EEG and ET measures as potential biomarkers in 3-5-year-old children with ASD and TD. To further evaluate the psychometric properties of the ET and EEG biomarkers in the 3-5 year old population.

Secondary Objectives:

* To collect blood samples from all ASD subjects and their biological parents for future genomic analyses and to share raw, processed, and analyzed data via the National Database for Autism Research (NDAR) and National Institute of Health / National Institute of Mental Health (NIH/NIMH) Data Repositories to create a community resource accessible for use by all qualified investigators.
* To compare estimates of key distributional parameters across the original, confirmation and feasibility samples to determine whether the markers profiles are sufficiently compatible to use in studies combining pre-school and school-aged children.

The Preschool Feasibility sample will be evenly divided (25 ASD, 25 TD), aged 3-5, with IQ ranging from 60-150, recruited from 5 clinical implementation sites in the US.

Endpoints:

To collect and analyze a new cohort of participants to evaluate the feasibility of ET and EEG acquisition in 3-5 year olds. We will also evaluate ET and EEG measures for potential utility as biomarkers in clinical trials. Primary endpoints include evaluation of (1) Acquisition, (2) Construct Validity, (3) Discriminant Validity.

Primary Biomarker Outcome Variables.

1. N170 Latency to Upright Human Faces: The N170 Latency to Upright Human Faces (N170 latency) is a scalp recorded EEG event-related potential (ERP) component elicited by perception of the upright human face. Recorded over the posterior-temporal right hemisphere, the latency (or speed) of the peak of the N170 ERP component occurs at approximately 200 msec in children aged 3 to 5 years of age.
2. Oculomotor Index of Gaze to Human Faces (OMI): Onscreen gaze position data, reflected in percentage of foveation (angling of the eyes to focus on a particular object) to human faces (Face%) relative to total valid foveation time across three assays.

Eligibility criteria: Inclusion Criteria:

For All Subjects:

1. Children (regardless of biological sex) Age 3 - 5. Participants must be able to complete the study before turning 6.
2. Written parental permission will be obtained prior to any study procedures. Child verbal assent will be obtained.
3. IQ 60-150 (ASD) and 80-150 (TD) as assessed by the Differential Ability Scales - 2nd Edition or developmental level via Mullen Scales of Early Learning Composite (ELC).
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 BOSA or Autism Diagnostic Observation Schedule (ADOS-2) and short form (ADI-R) scored age appropriately. 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 D1.

   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 D1.
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.

For ASD Participants (only):

1. Any known environmental circumstances that is likely to account for the picture of autism in the proband (severe nutritional or psychological deprivation etc.)

For TD Participants (only):

1. Known historical diagnosis of ASD or a sibling with ASD.
2. Criteria score in the ASD range on the BOSA/ADOS
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 (ECI-5 or CSI-4). 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: N170 Latency to Upright Human Faces
timeFrame: 1 Month
measure: Oculomotor Index of Gaze to Human Faces (OMI)
timeFrame: Baseline
measure: Oculomotor Index of Gaze to Human Faces (OMI)
timeFrame: 1 Month
Secondary outcomes:
measure: Aberrant Behavior Checklist (ABC)
timeFrame: Baseline
measure: Autism Impact Measure (AIM)
timeFrame: Baseline
measure: Behavior Assessment System for Children -3 (BASC-3)
timeFrame: Baseline
measure: PDD Behavior Inventory (PDD-BI)
timeFrame: Baseline
measure: Social Responsiveness Scale 2 (SRS-2)
timeFrame: Baseline
measure: Cognitive Assessment
timeFrame: Baseline
measure: Resting State EEG
timeFrame: Baseline
measure: Faces Processing EEG
timeFrame: Baseline
measure: Kaufman Assessment Battery for Children (K-ABC Face Recognition)
timeFrame: Baseline
measure: Emotional Competence Inventory (ECI)
timeFrame: Baseline
measure: Mullen Scales of Early Learning
timeFrame: Baseline
measure: VABS: Vineland Adaptive Behavior Scales- III Socialization
timeFrame: Baseline
measure: Eye-tracking (ET) Static Social Scenes Task
timeFrame: Baseline
measure: Eye-tracking (ET) Pupillary Light Reflex Task
timeFrame: Baseline
measure: Eye-tracking (ET) Social Interactive Task
timeFrame: Baseline
measure: Eye-Tracking (ET) Activity Monitoring Task
timeFrame: Baseline
measure: Visual Evoked Potentials (VEPs) EEG
timeFrame: Baseline
measure: Child Symptom Inventory-4 (CSI-4)
timeFrame: Baseline
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 University
state: North Carolina
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: Yale University
name: James McPartland, PhD
role: PRINCIPAL_INVESTIGATOR
References: