Immune Tests in Blood Samples From Children With ASD

In Vitro Immune Tests in Blood Samples From Children With ASD

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.

Study Overview

• Status: Recruiting
• Conditions: Autistic Disorder
• Intervention / Treatment: Diagnostic test: Blood draw; Diagnostic test: Stool Sample Collection; Diagnostic test: Urine Sample Collection

Detailed Description

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:

1. young children diagnosed with ASD
2. young children diagnosed with ASD and scheduled to undergo stem cell transplantation therapy (SCT)
3. age- and sex-matched typically developing children
4. high-risk infants (10-18 months) with at least one sibling with diagnosed ASD
5. 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.

• Study Type: Observational
• Enrollment (Anticipated): 550

Contacts and Locations

• Study Contact: Name: Benjamin Gesundheit, M.D.; Email: gesundheitmd@cell-el.com
• Study Contact Backup: Name: Leah Hochbaum; Email: leah@cell-el.com

Study Locations

• Israel
  • Jerusalem, Israel, 91031
    • Recruiting
    • Shaare Zedek Medical Center
    • Contact: Avraham Steinberg, MD; Email: avraham@steinberg.onmicrosoft.com
    • Principal Investigator: Avraham Steinberg, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 months to 12 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

• Male and female children, aged 2-12 years, diagnosed with ASD according to DSM- IV (299.00) or DSM-V (299.00) ± ADOS, ADIR, CARS, others
• Age- and sex-matched typically developing (TD) children
• Male and female children, aged 2-12 years, diagnosed with ASD according to DSM- IV (299.00) or DSM-V (299.00) ± ADOS, ADIR, CARS, others due to undergo SCT (Stem Cell Treatment)
• High-risk infants aged 10-18 months not diagnosed with ASD (Autism Spectrum Disorder) but with a sibling diagnosed with ASD
• Mothers of high-risk infants

Description

Inclusion Criteria:

1. Male and female children
2. 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
3. Informed consent signed by the parents

Exclusion Criteria:

1. Child and/or mother that have been treated with systemic steroids or have undergone immune suppression treatment within the last 6 months
2. Child and/or mother diagnosed with severe infectious diseases or sepsis over the last 6 months
3. Child with ASD treated for a severe convulsive disorder
4. Child and/or mother with hematological or malignant disorder
5. 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.

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Control Group of Children; 2-12 years old age & sex-matched controls - typically developing (TD) children	Diagnostic test: Blood draw; A blood sample (5 mL) will be collected.; Other Names: blood sample; venepuncture; Diagnostic test: Stool Sample Collection; Subjects will be provided a dry, plastic, screw-top specimen container and will be asked to collect a stool sample at home.; Other Names: Stool Analysis
Children-Autism Spectrum Disorder; 2-12 years old children diagnosed with ASD according to DSM-IV (299.00) or DSM-V (299.00)	Diagnostic test: Blood draw; A blood sample (5 mL) will be collected.; Other Names: blood sample; venepuncture; Diagnostic test: Stool Sample Collection; Subjects will be provided a dry, plastic, screw-top specimen container and will be asked to collect a stool sample at home.; Other Names: Stool Analysis
Children-Autism Spectrum Disorder+SCT; 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; A blood sample (5 mL) will be collected.; Other Names: blood sample; venepuncture; Diagnostic test: Stool Sample Collection; Subjects will be provided a dry, plastic, screw-top specimen container and will be asked to collect a stool sample at home.; Other Names: Stool Analysis; Diagnostic test: Urine Sample Collection; Subjects will be provided a dry, plastic, screw-top specimen container and will be asked to collect a urine sample at home.; Other Names: Urinalysis
High-risk infants; Infants aged 10-18 months not diagnosed with ASD but with a sibling diagnosed with ASD	Diagnostic test: Blood draw; A blood sample (5 mL) will be collected.; Other Names: blood sample; venepuncture; Diagnostic test: Stool Sample Collection; Subjects will be provided a dry, plastic, screw-top specimen container and will be asked to collect a stool sample at home.; Other Names: Stool Analysis
Mothers of high-risk infants; Mothers of recruited infants aged 10-18 months not diagnosed with ASD but with a sibling diagnosed with ASD	Diagnostic test: Blood draw; A blood sample (5 mL) will be collected.; Other Names: blood sample; venepuncture

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of discriminating microbiome signature among ASD vs.TD children	Finding immunological stool biomarkers that are ASD-specific	One day
Identification of discriminating microbiome signature among high-risk infants before vs. after ASD diagnosis, if diagnosed	Finding immunological stool biomarkers that can identify high-risk infants	Through study completion, up to 5 years
Identification of discriminating immunological profiles in blood of the mothers of high-risk infants	Finding immunological blood biomarkers that can identify mothers at risk of having an ASD child	One day

Collaborators and Investigators

• Sponsor: Benjamin Gesundheit
• Collaborators: Shaare Zedek Medical Center
• Investigators: Principal Investigator: Benjamin Gesundheit, MD, Cell El Ltd

Publications and helpful links

General Publications

• Gesundheit B, Rosenzweig JP, Naor D, Lerer B, Zachor DA, Prochazka V, Melamed M, Kristt DA, Steinberg A, Shulman C, Hwang P, Koren G, Walfisch A, Passweg JR, Snowden JA, Tamouza R, Leboyer M, Farge-Bancel D, Ashwood P. Immunological and autoimmune considerations of Autism Spectrum Disorders. J Autoimmun. 2013 Aug;44:1-7. doi: 10.1016/j.jaut.2013.05.005. Epub 2013 Jul 15.
• Gesundheit B, Zisman PD, Hochbaum L et al. Autism spectrum disorder diagnosis using a new panel of immune- and inflammatory-related serum biomarkers: A case-control multicenter study. Front. Pediatr (2023) https://doi.org/10.3389/fped.2023.967954

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2013
• Primary Completion (Anticipated): December 1, 2030
• Study Completion (Anticipated): December 1, 2030

Study Registration Dates

• First Submitted: June 19, 2014
• First Submitted That Met QC Criteria: June 19, 2014
• First Posted (Estimate): June 20, 2014

Study Record Updates

• Last Update Posted (Estimate): February 27, 2023
• Last Update Submitted That Met QC Criteria: February 23, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Inflammation; Autism; Risk Factors; Autoimmune Diseases; Autistic Disorder; Child Development Disorders; Pervasive
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder; Autistic Disorder
• Other Study ID Numbers: CellEL-920130030

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No