Biomarker of Children With Familial Autoimmune History

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Le Bonheur Children's Hospital
Sponsor:
Collaborator:
University of Tennessee Health Science Center
Information provided by (Responsible Party):
James W. Wheless, Le Bonheur Children's Hospital
ClinicalTrials.gov Identifier:
NCT01541033
First received: February 23, 2012
Last updated: October 13, 2014
Last verified: October 2014
  Purpose

The purpose of this study is to identify biomarkers in this subset of autism patients, design a protein based assay system for screening serum for these biomarkers and confirm that these serum antibodies are still present at one year's time.


Condition
Autism
Children

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Biomarker Discovery In Children With Autism Plus Familial Autoimmune History

Resource links provided by NLM:


Further study details as provided by Le Bonheur Children's Hospital:

Primary Outcome Measures:
  • Number of autistic participants with autoimmune markers [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    The designed techniques will be used to first identify and then determine the frequency of autoimmune markers cross reacting with fly neuronal proteins in children with carefully characterized autism with and without a positive familial autoimmune history (FAH) in a first degree relative compared to typically developing children without FAH.


Secondary Outcome Measures:
  • Identification of neuronal protein autoimmunity [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Presence of autoantibodies will be correlated with presence of a positive FAH in a first degree relative. Identification of neuronal protein autoimmunity will allow further investigation of etiological factors and possible immune modulating treatment in children with autism.


Biospecimen Retention:   Samples With DNA

Blood


Estimated Enrollment: 45
Study Start Date: November 2009
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
Autism with FAH
Children diagnosed with autism with first degree relatives that have autoimmune disorders.
Autism without FAH
Children diagnosed with autism without first degree relatives that have autoimmune disorders.
Control
Typically developing children

Detailed Description:

Purpose: To identify biomarkers in this subset of autism patients, design a protein based assay system for screening serum for these biomarkers and confirm that these serum antibodies are still present at one year's time.

Rationale: Autistic spectrum disorders (ASD), are an increasingly important public health concern. Estimates of prevalence of ASDs range from 1/500 to 1/150 children. Retrospective data points to immune dysfunction in some of these children and increased frequency of familial autoimmune history (FAH) has been reported in children with autism. Behavioral responses to immune modulating therapy, though in uncontrolled studies, indicate a role for autoimmunity in the pathogenesis. Preliminary prospective work has suggested an immune etiology in autism based on the high frequency of brain endothelial antibodies (BEA) in children with language regression, 2/3 of whom are on the autistic spectrum and with autism without language regression. Follow up studies in a small number of patients showed persistence of BEA after at least a year. The specific nervous system epitopes have not been identified.

Population: Approximately 15 children with clinically diagnosed autism who have first degree relatives (parents, brothers, sisters, or children) with autoimmune disorders listed on a questionnaire. Children on the autism spectrum without autoimmune history and sibling matched controls without an ASD from the Simons Foundation Autism Research Initiative (SFARI) with deidentified data in the SFARI database will be matched for age, sex and ethnicity. Plasma samples and psychometric data from the database will be provided through the database for analysis in the laboratory of Dr. Reiter.

Design: The investigators seek to identify protein biomarkers in the serum of children with carefully characterized autism who have a familial autoimmune history in first degree relatives (FAH). Cognitive defects in the mouse model of the autism spectrum disorder tuberous sclerosis complex can be ameliorated by rapamycin, an immune suppressant drug indicating the likelihood that auto-immunity plays a role in autism pathogenesis. To expedite the identification of these biomarkers the investigators will use proteomic profiling in Drosophila melanogaster. The Drosophila (fly) nervous system is highly homologous to humans at the molecular level and genetic pathways for synaptic development and function are highly conserved. Several human neurogenetic diseases including Huntington, Alzheimer, fragile X, spinal cerebellar ataxia and Parkinson disease have been successfully studied using fly genetic models. Monoclonal antibodies generated against total fly brain homogenate cross react with human neuronal tissue and are highly specific for the recognition of particular subsets of neurons in the human nervous system. Our goal is to identify biomarkers in this group of autism patients, design a protein based assay system for screening serum for these biomarkers and confirm that these serum antibodies are persistent. A similar approach was taken by Dr. Levin to identify the central nervous system (CNS) autoantigen in the human T-lymphotropic virus type 1 disease associated myelopathy/tropical spastic. Dr. Reiter's group currently uses proteomic profiling in Drosophila to identify the protein targets of the Angelman syndrome gene, UBE3A.

  Eligibility

Ages Eligible for Study:   4 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Children with or without autism

Criteria

Inclusion Criteria:

  • 4-17 years of age
  • male or female
  • autistic subjects must have a diagnosis of autism spectrum disorder

Exclusion Criteria:

  • Controls must have no diagnosis of autism spectrum disorder.
  • controls must be typically developing children without behavioral deviations.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01541033

Contacts
Contact: Tracee L Ridley, RN, MSN 901-287-5338 tracee.ridley@lebonheur.org

Locations
United States, Tennessee
LeBonheur Children's Hospital Recruiting
Memphis, Tennessee, United States, 38103
Principal Investigator: Kathryn A McVicar, MD         
Principal Investigator: Larry T Reiter, PhD         
LeBonheur Children's Hospital Recruiting
Memphis, Tennessee, United States, 38103
Contact: Tracee Ridley, RN, MSN    901-287-5338    Tracee.Ridley@lebonheur.org   
Principal Investigator: Kathryn A McVicar, MD         
Sponsors and Collaborators
Le Bonheur Children's Hospital
University of Tennessee Health Science Center
Investigators
Principal Investigator: Kathryn A McVicar, MD LeBonheur Children's Medical Center
Principal Investigator: Larry T Reiter, PhD LeBonheur Children's Medical Center
  More Information

No publications provided

Responsible Party: James W. Wheless, Departmental Chair, Le Bonheur Children's Hospital
ClinicalTrials.gov Identifier: NCT01541033     History of Changes
Other Study ID Numbers: 08-00206-XP
Study First Received: February 23, 2012
Last Updated: October 13, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Le Bonheur Children's Hospital:
autism
children

ClinicalTrials.gov processed this record on October 23, 2014