Treatment of Children With Autistic Spectrum Disorder With Autologous Umbilical Cord Blood, a Pilot Study

This study is a phase II, prospective, double blind, placebo-controlled study of the efficacy of autologous umbilical cord blood infusion.

The study population will consist of 60 children ages 18 months to 12 years with ASD. The population will be randomly assigned to 2 groups, the study group be treated by cord blood in the beginning of the study and the control group by placebo product.

The study will consist of 4 stages Stage 1: initial assessment by physiotherapist and occupational therapist / treatment by cord blood or placebo / blood work before and after treatment Stage 2: at stage 1 + 6 months assessment by physiotherapist and occupational therapist / cross-over treatment by cord blood or placebo / blood work before and after treatment Stage 4: at stage 1 + 12 months assessment by physiotherapist and occupational therapist The primary outcome is improvement of social communication skills six months after treatment at stage 1

Study Overview

• Status: Recruiting
• Conditions: Autistic Spectrum Disorder
• Intervention / Treatment: Biological: Placebo; Biological: Autologous umbilical cord blood

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Omer Bar-Yosef, MD.PHD; Phone Number: 972-35302895; Email: Omer.BarYosef@sheba.health.gov.il

Study Locations

• Israel
  • Ramat Gan, Israel
    • Recruiting
    • Chaim Seba Medical Center
    • Contact: Omer Bar-Yosef

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 1.5 years to ≤ 12 years (11 years, 364 days) at the time of visit 1
• Confirmed clinical DSM-5 diagnosis of Autism Spectrum Disorder using the DSM-5 criteria
• Fragile X testing performed and negative
• Available and qualified umbilical cord blood unit with a minimum banked total nucleated cell dose of ≥ 2 x 10e7 cells/kg
• Stable on current psychiatric medication regimen (dose and dosing schedule) for at least 2 months prior to infusion of study product
• Normal absolute lymphocyte count (≥1500/uL)
• Able to travel to Sheba Medical Center University three times (baseline, 6 and 12 months post-baseline), and parent/guardian is able to participate in interim surveys and interviews monthly
• Parental consent

Exclusion Criteria

• General:

  • Review of medical records indicates ASD diagnosis not likely
  • Known diagnosis of any of the following coexisting psychiatric conditions: depression, bipolar disorder, schizophrenia, obsessive compulsive disorder
  • Screening data suggests that participant would not be able to comply with the requirements of the study procedures, including study outcome measures, as assessed by the study team
  • Family is unwilling or unable to commit to participation in all study-related assessments, including follow up for approximately 12 months

• Genetic:

  • Records indicate that child has a known genetic syndrome such as (but not limited to) Fragile X syndrome, neurofibromatosis, Rett syndrome, tuberous sclerosis, PTEN mutation, cystic fibrosis, muscular dystrophy
  • Known pathogenic copy number variation (CNV) associated with ASD (e.g., 16p11.2, 15q13.2, 2q13.3)

• Infectious:

  • Known active CNS infection
  • Evidence of uncontrolled infection based on records or clinical assessment
  • HIV positivity

• 4 Medical:

  • Known metabolic disorder
  • Known mitochondrial dysfunction
  • History of unstable epilepsy or uncontrolled seizure disorder, Lennox Gastaut syndrome, Dravet syndrome, or other similar epileptic encephalopathy
  • Concurrent genetic or acquired disease or comorbidity(ies) that could require a future stem cell transplant
  • Significant sensory (e.g., blindness, deafness, uncorrected hearing impairment) or motor (e.g., cerebral palsy) impairment
  • Evidence of clinically relevant physical dysmorphology indicative of a genetic syndrome as assessed by the PIs or other investigators, including a medical geneticist and psychiatrists trained in identifying dysmporphic features associated with neurodevelopmental conditions.

• Current/Prior Therapy:

  • History of prior cell therapy
  • Current or prior use of IVIG or other anti-inflammatory medications with the exception of NSAIDs
  • No systemic steroid therapy that has lasted >2 weeks, and no systemic steroids within 3 months prior to enrollment. Topical and inhaled steroids are permitted.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: group 1; Autologous umbilical cord blood transfusion Single dose of an Autologous umbilical cord blood transfusion	Biological: Autologous umbilical cord blood; Single infusion of autologous umbilical cord blood cells
Experimental: group 2; The placebo product will consist of the standard ingredients of the acellular content of the UCB unit. It will consist of 20 ml Dextran (Plander 40.000 - 50g/500ml, solution for infusion) and 20 ml of human Albumin 5% (solution for infusion). The volume of placebo product will be 40 ml,	Biological: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement of social communication skills	Vineland Adaptive Behavior Scales-Second Edition (VINELAND-II)	6 months
Improvement of social communication skills	Pediatric Evaluation of Disability Inventory-Computer Adaptive Test-ASD	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement of social communication skills	Theory of Mind Inventory - 2	6 months
Functional assessment	Adaptive Behavior Assessment System - Second edition (ABAS-2)	6 months

Collaborators and Investigators

• Sponsor: Sheba Medical Center
• Investigators: Principal Investigator: Omer Bar-Yosef, MD.PHD, Sheba Medical Center

Publications and helpful links

General Publications

• Lai MC, Lombardo MV, Baron-Cohen S. Autism. Lancet. 2014 Mar 8;383(9920):896-910. doi: 10.1016/S0140-6736(13)61539-1. Epub 2013 Sep 26.
• Christensen DL, Baio J, Van Naarden Braun K, Bilder D, Charles J, Constantino JN, Daniels J, Durkin MS, Fitzgerald RT, Kurzius-Spencer M, Lee LC, Pettygrove S, Robinson C, Schulz E, Wells C, Wingate MS, Zahorodny W, Yeargin-Allsopp M; Centers for Disease Control and Prevention (CDC). Prevalence and Characteristics of Autism Spectrum Disorder Among Children Aged 8 Years--Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2012. MMWR Surveill Summ. 2016 Apr 1;65(3):1-23. doi: 10.15585/mmwr.ss6503a1. Erratum In: MMWR Morb Mortal Wkly Rep. 2016;65(15):404. MMWR Morb Mortal Wkly Rep. 2018 Nov 16;67(45):1279.
• Prata J, Santos SG, Almeida MI, Coelho R, Barbosa MA. Bridging Autism Spectrum Disorders and Schizophrenia through inflammation and biomarkers - pre-clinical and clinical investigations. J Neuroinflammation. 2017 Sep 4;14(1):179. doi: 10.1186/s12974-017-0938-y.

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2020
• Primary Completion (Anticipated): December 1, 2024
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: January 15, 2020
• First Submitted That Met QC Criteria: January 25, 2020
• First Posted (Actual): January 28, 2020

Study Record Updates

• Last Update Posted (Actual): January 20, 2021
• Last Update Submitted That Met QC Criteria: January 17, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Autistic Spectrum Disorder, autologous umblical cord blood
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Neurodevelopmental Disorders; Disease; Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive
• Other Study ID Numbers: SHEBA-18-5105-OBY-CTIL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Yes data set of the baseline of the children, the quantity of cord blood transfusion they received and the clinical followup information.
• IPD Sharing Time Frame: within 2 years from the end of data collection
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

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