Proteomic Biomarker Tests in Blood Samples from Children with Autism Spectrum Disorder (ASD)

NCT02168868 | Recruiting DMC

• 1 other identifier: CellEL-920130030
• Study Type: observational
• Target: 900
• Locations: 1 country
• Sites: 1

Brief Summary

Behavioral testing is the gold standard for diagnosing autism spectrum disorder (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. To date, no definitive treatment exists for ASD. Most therapies are symptom-focused, generally focusing on behavioral, social and communication skills. Recent works have reported on promising outcomes of mesenchymal stem cell (MSC) treatment of children with ASD. MSCs are multipotent, non-hematopoietic, easily isolatable and expandable stem cells involved in tissue repair, immunomodulatory responses and neuromodulation. MSC treatment of children with ASD has reportedly led to improvements in speech, sociability, eye coordination, balance, cognition and overall well-being. At the base of this approach lies the known plasticity of the human brain and immune system in the early childhood years and the ability of MSCs to modulate atypical inflammatory and immune activities. Assessment of ASD biomarker profiles in children with ASD who have undergone one or more SCT sessions may shed light on the mechanism of action, assist in better defining ASD-specific diagnostic markers and monitor treatment outcomes.

Conditions

Autistic Disorder

Keywords

Autoimmune Diseases; Child Development Disorders; Inflammation; Risk Factors; Pervasive; Autism; Autistic Disorder

Outcome Measures

Primary Outcomes (3)

• Identification of discriminating proteomic biomarker profile in blood of children with ASD vs. matched TD children

  Finding a proteomic signature in children with ASD

  One day

• Identification of discriminating proteomic biomarker profiles in blood of high-risk infants, at recruitment vs. after diagnosis of ASD, if diagnosed

  Finding a proteomic signature in infants at high-risk of ASD

  Up to 5 years after initial blood draw

• Comparison of blood biomarker profiles in ASD children before versus after SCT

  Finding ASD-specific blood proteomic biomarkers that can be modified by SCT

  Through study completion, up to 6 months

Secondary Outcomes (2)

• ASD severity vs. blood biomarker levels

  Through study, up to 5 years, depending on cohort

• Blood biomarker levels and SCT outcomes

  Through study completion, up to 6 months

Other Outcomes (5)

• Identification of ASD-specific proteomic biomarkers and/or microbiome profile in stool samples of children with ASD before vs. after SCT

  Up to 6 months

• Comparison of urine biomarker profiles in ASD children before versus after SCT

  Up to 6 months

• Identification of ASD-specific proteomic biomarker and microbiome signature in stool samples of high-risk infants before vs. after ASD diagnosis, if diagnosed

  Through study completion, up to 5 years

Study Arms (6)

Control Group of Young Children

2-12 years old age \& sex-matched controls - typically developing (TD) children

Diagnostic Test: Blood draw

Young 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

Young 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; Diagnostic Test: Stool Sample Collection; Diagnostic Test: Urine Sample Collection

High-risk infants

Infants aged 10-19 months not diagnosed with ASD but with a sibling diagnosed with ASD

Diagnostic Test: Blood draw; Diagnostic Test: Stool Sample Collection

Mothers of high-risk infants

Mothers of recruited infants aged 10-19 months not diagnosed with ASD but with a sibling diagnosed with ASD

Diagnostic Test: Blood draw

Adolescent-Autism Spectrum Disorder+SCT

12-18 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; Diagnostic Test: Stool Sample Collection; Diagnostic Test: Urine Sample Collection

Interventions

Blood draw DIAGNOSTIC_TEST

A blood sample (5 mL) will be collected.

Also known as: blood sample, venepuncture

Adolescent-Autism Spectrum Disorder+SCT; Control Group of Young Children; High-risk infants; Mothers of high-risk infants; Young Children-Autism Spectrum Disorder; Young Children-Autism Spectrum Disorder+SCT

Stool Sample Collection DIAGNOSTIC_TEST

Subjects will be provided a dry, plastic, screw-top specimen container and will be asked to collect a stool sample at home.

Also known as: Stool Analysis

Adolescent-Autism Spectrum Disorder+SCT; High-risk infants; Young Children-Autism Spectrum Disorder+SCT

Urine Sample Collection DIAGNOSTIC_TEST

Subjects will be provided a dry, plastic, screw-top specimen container and will be asked to collect a urine sample at home.

Also known as: Urinalysis

Adolescent-Autism Spectrum Disorder+SCT; Young Children-Autism Spectrum Disorder+SCT

Eligibility Criteria

• Age: 10 Months - 19 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

1. Up to a total of 350 male and female children, aged 2-12 years, diagnosed with ASD according to DSM-IV (299.00) or DSM-V (299.00) 2. Up to a total of 350 male and female typically developing (TD) children aged 2-12 years with no signs of ASD or history of ASD in the immediate family who will serve as controls for the main subset of children with ASD 3. Up to 50 infants aged 10-19 months not diagnosed with ASD but with a sibling diagnosed with ASD according to DSM-IV (299.00) or DSM-V (299.00) (herein, high-risk infants) 4. Up to 50 mothers of the high-risk infants participating in the study 5. Up to 50 male and female children, aged 2-12 years, diagnosed with ASD according to DSM-IV (299.00) or DSM-V (299.00) scheduled to undergo stem cell therapy (SCT) 6. Up to 50 male and female children, aged 12-18 years, diagnosed with ASD according to DSM-IV (299.00) or DSM-V (299.00) scheduled to undergo SCT

You may qualify if:

• Male and female children
• Child aged 2-12 years with diagnosed ASD according to Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV (299.00) or DSM-V (299.00) OR Child aged 2-18 years diagnosed ASD according to DSM-IV (299.00) or DSM-V (299.00) AND scheduled to undergo stem cell transplantation OR Child aged 10-19 months not diagnosed with ASD but with a sibling diagnosed with ASD according to (DSM)-IV (299.00) or DSM-V (299.00) (herein termed "high-risk infants") OR Mothers of recruited high-risk infants OR A typically developing child aged 2-12 years with no signs of ASD or history of ASD in the immediate family
• Informed consent signed by the parent/legal guardian

You may not qualify if:

• Child and/or mother completed treatment with systemic steroids or immune suppressants less than 4 weeks before the screening visit
• 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 (intractable seizures)
• Child and/or mother with hematological or malignant disorder
• For children in the SCT cohort: No new planned immune-modulating treatment (other than SCT) for at least 6 months before or after planned stem cell transplantation date
• If the PI suspects that the participant will not comply with study requirements, the participant may be excluded.

Sponsors & Collaborators

• Benjamin Gesundheit: lead
• Shaare Zedek Medical Center: collaborator

Study Sites (1)

Shaare Zedek Medical Center

Jerusalem, 91031, Israel

RECRUITING

Related Publications (2)

• 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.

  PMID: 23867105 BACKGROUND

• Gesundheit B, Zisman PD, Hochbaum L, Posen Y, Steinberg A, Friedman G, Ravkin HD, Rubin E, Faktor O, Ellis R. Autism spectrum disorder diagnosis using a new panel of immune- and inflammatory-related serum biomarkers: A case-control multicenter study. Front Pediatr. 2023 Feb 21;11:967954. doi: 10.3389/fped.2023.967954. eCollection 2023.

  PMID: 36896401 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood, urine and stool samples.

MeSH Terms

Conditions

Autistic Disorder; Autoimmune Diseases; Developmental Disabilities; Inflammation

Interventions

Blood Specimen Collection; Occult Blood; Urinalysis

Condition Hierarchy (Ancestors)

Autism Spectrum Disorder; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Clinical Chemistry Tests; Diagnostic Techniques, Urological

Study Officials

• Benjamin Gesundheit, MD

  Cell El Ltd

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Benjamin Gesundheit, M.D.

CONTACT

gesundheitmd@cell-el.com

Leah Hochbaum

CONTACT

leah@cell-el.com

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Target Duration: 1 Day
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: CEO

Study Record Dates

• First Submitted: June 19, 2014
• First Posted: June 20, 2014
• Study Start: May 1, 2013
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030
• Last Updated: November 25, 2024

Record last verified: 2023-02

Locations

IL (1)