Improving Autism Screening With Brain-Related miRNA

Study Overview
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Brief Summary
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The goal of this project is to identify specific miRNAs that are increased or decreased in the saliva of children with developmental delay and are useful for screening toddlers for ASD. Such a screening tool would improve the specificity of diagnosis, streamline referrals to developmental specialists, and expedite the arrangement of early intervention services.

Detailed Description
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The central aim of this project is to characterize the expression of exosomal microRNA (miRNA) in children with autism spectrum disorder (ASD). Currently, the CDC estimates the prevalence of ASD in U.S. children to be 1 in 68. Yet, the biological causes, diagnosis, and treatment of this disease remain ambiguous. Growing evidence implicates a genetic role in ASD. miRNAs regulate genetic expression and are altered in lymphocytes, neurons and serum of patients with ASD. Recent studies of miRNAs have shown that they can be packaged into exosomal vessels and extruded from neurons as extracellular signaling tools. This knowledge provides a novel approach for examining the genetic regulation of the central nervous system. We propose to measure the expression of extracellular miRNA in children with ASD. Expression levels of miRNA from blood and saliva will be compared between children with autism and normally developing controls. The goal of this study will be to identify genetic regulatory mechanisms involved in ASD and provide potential biomarkers for diagnostic screening. The primary endpoints of this study are as follows: Characterization of brain-related miRNA in the saliva of children with ASD and typically developing control children between the ages of two and five years. Identification of sets of miRNAs in saliva and plasma that are predictive of both ASD diagnosis and severity of ASD symptoms. This aim will enroll ASD and control children age 12-24 months (inclusive). Secondary endpoints include the identification of miRNA expression patterns that correlate with ASD symptom severity measured with standardized neuropsychologic testing and to characterize parental knowledge and attitudes towards epigenetic testing in the context of ASD..

Official Title
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Improving Autism Screening With Brain-Related miRNA

Conditions
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Developmental Delay, Autism Spectrum Disorder

Intervention / Treatment
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* Other: Saliva collection
* Other: Vineland Adaptive Behavior Scale-II Assessment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Age at enrollment: 18 months and 6 years (inclusive) Control group documented negative ASD screening on M-CHAT-R ASD group: established DSM-5 diagnosis Parent/guardian must be fluent in written and spoken English (required to complete study specific questionnaires etc) Exclusion Criteria: For autistic subjects study exclusion criteria will include: • Autistic subjects with known syndromic autism (attributed to a known genetic mutation) Control subjects only exclusion criteria will include: • A diagnosis of autism For both groups: wards of the state, active periodontal infection, active upper respiratory infection

Ages Eligible for Study
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Minimum Age: 18 Months
Maximum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Autism Spectrum Disorder (ASD)<br>Age at enrollment: 18 months to 6 years with established DSM-5 diagnosis of autism spectrum disorder. Exclusion criteria include: wards of the state syndromic autism (attributed to a known genetic mutation) active periodontal infection active upper respiratory infection | Other: Saliva collection<br>* Collection of saliva via swab for miRNA processing<br>Other: Vineland Adaptive Behavior Scale-II Assessment<br> <br> |
| Control<br>Age 18 months to 6 years without autism spectrum disorder (may have typical development or developmental delay without autism - as defined by negative MCHAT-R or negative ADOS-II evaluation) Exclusion criteria include: wards of the state active periodontal infection active upper respiratory infection | Other: Saliva collection<br>* Collection of saliva via swab for miRNA processing<br>Other: Vineland Adaptive Behavior Scale-II Assessment<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| salivary miRNA profile | Measures of miRNA abundance in saliva | at time of collection (between 18 months and 6 years of age) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measures of adaptive function | Vineland adaptive behavior composite score | at time of enrollment (between 18 months and 6 years) | 
| Measure of autistic behavior | Autism Diagnostic Observation Schedule (ADOS) Composite Score (when clinically indicated) | at time of enrollment (between 18 months and 6 years) |