Immune Tests in Blood Samples From Children With ASD

Study Overview
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Brief Summary
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Behavioral testing is the gold standard for diagnosing ASD. These tests, including ADOS and ADI-R, are subjective, require trained staff to administer, are time-consuming, and can only be administered at a later age. Blood-, urine- or stool-based diagnostic biomarker test for ASD would enable objective early diagnosis, potentially even before clinical symptoms are present, eliminate the need for trained staff and enable early intervention. Such a test would not only conserve money and time but would also provide clues to ASD pathogenesis.

Detailed Description
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There is accumulating evidence that at least a subset of children diagnosed with ASD also have aberrant immune functions. This study will attempt to identify more specifically the nature of the potential immune abnormalities in children. The study will follow a case-control design, involving the following cohorts: young children diagnosed with ASD young children diagnosed with ASD and scheduled to undergo stem cell transplantation therapy (SCT) age- and sex-matched typically developing children high-risk infants (10-18 months) with at least one sibling with diagnosed ASD mothers of these high-risk infants Parents will be asked to complete several questionnaires relating to demographic and anamnestic details and to the child's development. A single blood draw will be performed in the clinic and single stool and urine samples will be collected at home. For children scheduled to undergo SCT, the blood, stool and urine samples must be collected before therapy. For participating mothers, only a single blood sample will be collected (no stools or urine samples). Parents of high-risk infants will be contacted by phone or email when the child reaches diagnosable age (3.5 years) and again at the age of 6 years, to obtain an update on the child's ASD status. If the child has been diagnosed with ASD, an additional blood and stool sample may be collected. Children who underwent SCT will be contacted 2±1 months and 6±1 months after the first treatment session, for collection of additional blood samples. Stool and urine samples will be collected at the 6±1 month post-treatment visit as well. Should the child undergo additional SCT within two years of the first treatment, additional blood, stool and urine samples may be collected. At each subsequent visit, a parent/legal guardian will be asked to complete several short questionnaires. Adverse events to blood drawing will be reported to the Data Coordinating Center using the appropriate Case Report Form (CRF). In cases of adverse effects (AE) related to the drawing of blood or performance of examination of patients in the course of standard examination procedures, the investigating team will proceed in accordance with local guidelines (to be inserted by the PI), reporting the incidents which occurred during the course of a clinical trial. Clinical data will be collected by the investigator, or a person appointed and appropriately trained by the investigator, and shall be entered into standardized CRFs and shared online with the sponsor. Source data will be retained for all data entered in the CRFs. Progress reports and the Final Report at the conclusion of the trial will be submitted to the regulatory authority and the Ethics Committee, as required.

Official Title
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In Vitro Immune Tests in Blood Samples From Children With ASD

Conditions
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Autistic Disorder

Intervention / Treatment
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* Diagnostic Test: Blood draw
* Diagnostic Test: Stool Sample Collection
* Diagnostic Test: Urine Sample Collection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female children Child aged 2-12 with diagnosed autism spectrum disorder (ASD) according to Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV (299.00) or DSM-V (299.00) ± ADOS OR Child aged 2-12 diagnosed autism spectrum disorder (ASD) according to Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV (299.00) or DSM-V (299.00) ± ADOS AND scheduled to undergo stem cell transplantation OR Child aged 10-18 months not diagnosed with ASD but with a sibling diagnosed with ASD according to Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV (299.00) or DSM-V (299.00) ± ADOS (herein termed high-risk infants) OR Mothers of high-risk infants OR A typically developing child aged 2 to 12 years with no signs of ASD or history of ASD in the immediate family Informed consent signed by the parents Exclusion Criteria: Child and/or mother that have been treated with systemic steroids or have undergone immune suppression treatment within the last 6 months Child and/or mother diagnosed with severe infectious diseases or sepsis over the last 6 months Child with ASD treated for a severe convulsive disorder Child and/or mother with hematological or malignant disorder For children in the SCT cohort: No new planned treatment (other than SCT) for at least 6 months from planned stem cell transplantation date and no new treatments (other than SCT) started within 6 months before planned transplantation date.

Ages Eligible for Study
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Minimum Age: 10 Months
Maximum Age: 12 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 |
| --- | --- |
| Control Group of Children<br>2-12 years old age & sex-matched controls - typically developing (TD) children | Diagnostic Test: Blood draw<br>* A blood sample (5 mL) will be collected.<br>* Other names: venepuncture;Diagnostic Test: Stool Sample Collection<br>* Subjects will be provided a dry, plastic, screw-top specimen container and will be asked to collect a stool sample at home.<br>* Other names: Stool Analysis;|
| Children-Autism Spectrum Disorder<br>2-12 years old children diagnosed with ASD according to DSM-IV (299.00) or DSM-V (299.00) | Diagnostic Test: Blood draw<br>* A blood sample (5 mL) will be collected.<br>* Other names: venepuncture;Diagnostic Test: Stool Sample Collection<br>* Subjects will be provided a dry, plastic, screw-top specimen container and will be asked to collect a stool sample at home.<br>* Other names: Stool Analysis;|
| Children-Autism Spectrum Disorder+SCT<br>2-12 years old children diagnosed with ASD according to DSM-IV (299.00) or DSM-V (299.00) due to undergo stem cell transplantation therapy | Diagnostic Test: Blood draw<br>* A blood sample (5 mL) will be collected.<br>* Other names: venepuncture;Diagnostic Test: Stool Sample Collection<br>* Subjects will be provided a dry, plastic, screw-top specimen container and will be asked to collect a stool sample at home.<br>* Other names: Stool Analysis;Diagnostic Test: Urine Sample Collection<br>* Subjects will be provided a dry, plastic, screw-top specimen container and will be asked to collect a urine sample at home.<br>* Other names: Urinalysis;|
| High-risk infants<br>Infants aged 10-18 months not diagnosed with ASD but with a sibling diagnosed with ASD | Diagnostic Test: Blood draw<br>* A blood sample (5 mL) will be collected.<br>* Other names: venepuncture;Diagnostic Test: Stool Sample Collection<br>* Subjects will be provided a dry, plastic, screw-top specimen container and will be asked to collect a stool sample at home.<br>* Other names: Stool Analysis;|
| Mothers of high-risk infants<br>Mothers of recruited infants aged 10-18 months not diagnosed with ASD but with a sibling diagnosed with ASD | Diagnostic Test: Blood draw<br>* A blood sample (5 mL) will be collected.<br>* Other names: venepuncture;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of discriminating immunological profiles in blood of children with ASD vs. matched TD children | Finding immunological blood biomarkers that are ASD-specific | One day | 
| Identification of discriminating immunological profiles in blood of high-risk infants, at recruitment vs. after diagnosis of ASD, if diagnosed | Finding immunological biomarkers that may identify high-risk populations | Through study, up to 5 years, depending on cohort | 
| Comparison of biomarker profiles in ASD children before versus after SCT | Finding ASD-specific immunological biomarkers that can be modified by treatment | Through study completion, up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ASD severity vs. biomarker levels | Correlative assessment of ASD severity vs. biomarker levels | Through study, up to 5 years, depending on cohort | 
| Biomarker levels and SCT outcomes | Correlative assessment of biomarker levels and SCT outcomes | Through study completion, up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autoimmune Diseases, Child Development Disorders, Inflammation, Risk Factors, Pervasive, Autism, Autistic Disorder