Improving Autism Screening With Brain-Related miRNA

Autism Spectrum Disorder Clinical Trial

Official title:

Improving Autism Screening With Brain-Related miRNA

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02712853
• Other study ID #: Study00003658
• Status: Completed
• Start date: November 2015
• Est. completion date: August 2018

Study information

• Verified date: August 2018
• Source: Milton S. Hershey Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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:

1. 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.

2. 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..

Recruitment information / eligibility

• Status: Completed
• Enrollment: 304
• Est. completion date: August 2018
• Est. primary completion date: August 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Months to 6 Years

Eligibility

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

Related Conditions & MeSH terms

• Autism Spectrum Disorder
• Autistic Disorder
• Developmental Delay

Intervention

Other:
• Saliva collection
Collection of saliva via swab for miRNA processing
• Vineland Adaptive Behavior Scale-II Assessment

Locations

Country	Name	City	State
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Milton S. Hershey Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (3)

Abu-Elneel K, Liu T, Gazzaniga FS, Nishimura Y, Wall DP, Geschwind DH, Lao K, Kosik KS. Heterogeneous dysregulation of microRNAs across the autism spectrum. Neurogenetics. 2008 Jul;9(3):153-61. doi: 10.1007/s10048-008-0133-5. Epub 2008 Jun 19. — View Citation

Mundalil Vasu M, Anitha A, Thanseem I, Suzuki K, Yamada K, Takahashi T, Wakuda T, Iwata K, Tsujii M, Sugiyama T, Mori N. Serum microRNA profiles in children with autism. Mol Autism. 2014 Jul 30;5:40. doi: 10.1186/2040-2392-5-40. eCollection 2014. — View Citation

Sarachana T, Zhou R, Chen G, Manji HK, Hu VW. Investigation of post-transcriptional gene regulatory networks associated with autism spectrum disorders by microRNA expression profiling of lymphoblastoid cell lines. Genome Med. 2010 Apr 7;2(4):23. doi: 10.1186/gm144. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	salivary miRNA profile	Measures of miRNA abundance in saliva	at time of collection (between 18 months and 6 years of age)
Secondary	Measures of adaptive function	Vineland adaptive behavior composite score	at time of enrollment (between 18 months and 6 years)
Secondary	Measure of autistic behavior	Autism Diagnostic Observation Schedule (ADOS) Composite Score (when clinically indicated)	at time of enrollment (between 18 months and 6 years)