Improving Autism Screening With Brain-Related miRNA

NCT ID: NCT02712853

Last Updated: 2018-08-22

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 304 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-11-30
• Study Completion Date: 2018-08-31

Brief 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.

Detailed 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..

Conditions

Autism Spectrum Disorder; Developmental Delay

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Autism Spectrum Disorder (ASD)

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

Saliva collection

Intervention Type: OTHER

Collection of saliva via swab for miRNA processing

Vineland Adaptive Behavior Scale-II Assessment

Intervention Type: OTHER

Control

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

Saliva collection

Intervention Type: OTHER

Collection of saliva via swab for miRNA processing

Vineland Adaptive Behavior Scale-II Assessment

Intervention Type: OTHER

Interventions

Saliva collection

Collection of saliva via swab for miRNA processing

Intervention Type: OTHER

Vineland Adaptive Behavior Scale-II Assessment

Intervention Type: OTHER

Eligibility Criteria

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

• Autistic subjects with known syndromic autism (attributed to a known genetic mutation)

• A diagnosis of autism

For both groups: wards of the state, active periodontal infection, active upper respiratory infection

• Minimum Eligible Age: 18 Months
• Maximum Eligible Age: 6 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Milton S. Hershey Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Steven Hicks

Assistant Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Steven Hicks, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Milton S. Hershey Medical Center

Locations

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 25126405 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20374639 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18563458 (View on PubMed)

Other Identifiers

Study00003658

Identifier Type: -

Identifier Source: org_study_id