The Autism Biomarkers Consortium for Clinical Trials
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 565
- 试验地点
- 5
- 主要终点
- N170 Latency to Upright Human Faces
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 6 Years 至 11 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •For All Subjects:
- •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).
- •Written parental permission, and child assents when applicable, obtained prior to any study procedures.
- •IQ 60-150 (ASD) and 80-150 (TD) as assessed by the Differential Ability Scales - 2nd Edition.
- •Participant and parent/guardian must be English speaking.
- •For ASD Participants (only):
- •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.
- •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.
排除标准
- •For All Subjects:
- •Known genetic or neurological syndrome with an established link to autism (in addition to ASD for ASD participants)
- •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).
- •Specific cases will be discussed with the clinical team who will make a final determination, as needed.
- •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.
- •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.
- •Children who are taking neurological or psychiatric medications that are not stable on prescription or dose for 8 weeks prior to T1D
- •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 T1D
- •History of significant prenatal/perinatal/birth injury as defined by birth <36 weeks AND weight <2000 grams (approximately 4.5.lbs).
- •History of neonatal brain damage. (e.g., with diagnosed hypoxic or ischemic event).
- •Any other factor that the investigator feels would make assessment or measurement performance invalid.
- •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):
- •Known historical diagnosis of ASD or a sibling with ASD.
- •Criteria score in the ASD range on the ADOS/BOSA at T1
- •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 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.
结局指标
主要结局
N170 Latency to Upright Human Faces
时间窗: 24 weeks
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 6 to 11 years of age.
Oculomotor Index of Gaze to Human Faces (OMI)
时间窗: 24 weeks
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.
VABS: Vineland Adaptive Behavior Scales- III Socialization
时间窗: 24 weeks
Administered in person visit or via parent phone interview. The Socialization score is based on 3 subdomains of Interpersonal Relationships, Play \& Leisure, Coping Scales. The V-Scaled scores, which are specifically designed to measure change over time, are only available for the subdomains. The primary norm-referenced scores for the subdomains are v-scale scores, which have a mean of 15 and standard deviation (SD) of 3. The Vineland-3 is a standardized measure of adaptive behavior--the things that people do to function in their everyday lives.
次要结局
- Autism Impact Measure (AIM)(Baseline, 6 weeks and 24 weeks)
- Child and Adolescent Symptom Inventory 5 (CASI-5)(Baseline and 24 weeks)
- PDD Behavior Inventory (PDD-BI)(Baseline, 6 weeks and 24 weeks)
- Eye-tracking (ET) Pupillary Light Reflex Task(Baseline, 6 weeks and 24 weeks)
- Eye-tracking (ET) Static Social Scenes Task(Baseline, 6 weeks and 24 weeks)
- Aberrant Behavior Checklist (ABC)(Baseline, 6 weeks and 24 weeks)
- Social Responsiveness Scale 2 (SRS-2)(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.)
- Faces Processing EEG(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)
- Behavior Assessment System for Children -3 (BASC-3)(Baseline)
- Cognitive Assessment(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)
- Resting State EEG(Baseline, 6 weeks and 24 weeks)
- Eye-Tracking (ET) Activity Monitoring Task(Baseline, 6 weeks and 24 weeks)
- Visual Evoked Potentials (VEPs) EEG(Baseline, 6 weeks and 24 weeks)
- Eye-tracking (ET) Interactive Social Task (IST)(Baseline, 6 weeks and 24 weeks)
- NEPSY-II(Baseline, 6 weeks and 24 weeks)
研究者
James C. McPartland
Professor - Child Study Center
Yale University