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

Study Overview
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Brief Summary
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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

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

Conditions
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Autistic Spectrum Disorder

Intervention / Treatment
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* Biological: Autologous umbilical cord blood
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Months
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: group 1<br>Autologous umbilical cord blood transfusion Single dose of an Autologous umbilical cord blood transfusion | Biological: Autologous umbilical cord blood<br>* Single infusion of autologous umbilical cord blood cells<br>|
| Experimental: group 2<br>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<br>* Placebo<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autistic Spectrum Disorder, autologous umblical cord blood