Autologous Umbilical Cord Blood Infusion for Children With Autism Spectrum Disorder (ASD)

Study Overview
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Brief Summary
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This study is a prospective phase 1 single-center trial designed to determine the safety of a single intravenous infusion of autologous umbilical cord blood in children with Autism Spectrum Disorder (ASD) and assess the feasibility of various outcome measures to determine which measure(s) can be used as primary and secondary endpoints for a future randomized phase 2 clinical trial. All subjects will receive infusion of cord blood cells at baseline with follow up assessments at 6 and 12 months.

Detailed Description
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Autism Spectrum Disorder (ASD) is a neurodevelopment disorder with early onset in life. Currently, available treatments for patients with ASD are supportive, but not curative. Umbilical cord blood (UCB) has been shown to lessen the clinical and radiographic impact of hypoxic brain injury and stroke in animal models and in infants with hypoxic ischemic encephalopathy. UCB also engrafts and differentiates in the brain, facilitating neural cell repair in animal models and human patients with inborn errors of metabolism undergoing allogeneic, unrelated donor UCB transplantation. Infusion of autologous UCB does not require immunosuppression and has been shown to be safe in young children with brain injuries such as cerebral palsy and stroke. In this study, the investigators hypothesize that infusion of a patient's own umbilical cord blood cells (UCB) can offer neural protection/repair in the brain and reduction of inflammation associated with this disorder.

Official Title
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Autologous Umbilical Cord Blood Infusion for Children With Autism Spectrum Disorder (ASD)

Conditions
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Autism Spectrum Disorder

Intervention / Treatment
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* Biological: Autologous Umbilical Cord Blood


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 24 months to ≤72months at the time of visit 1 Confirmed clinical DSM-5 diagnosis of Autism Spectrum Disorder using all three of the following measures: Autism Diagnostic Observation Schedule - Toddler or Generic (ADOS) Autism Diagnostic Interview-Revised (ADI-R) DSM-5 checklist IQ ≥ 35 on Stanford Binet Intelligence Scale or similar standardized test Autologous umbilical cord blood available from a cord blood bank with a minimum total nucleated cell dose of ≥ 1 x 107 cells/kilogram of subject weight that meets acceptance criteria outlined in section 6.0 with confirmed HLA matching Stable on current medications for at least 2 months prior to infusion of cord blood Ability to travel to Duke University three times (0, 6, 12 mo.), parent/guardian able to participate in electronic communication tracking two times in the study and interim phone surveys every 3 months Parental consent Subject and parent/guardian must be English speaking Exclusion Criteria: Unwilling to commit to follow up for a year History of prior cell therapy Use of IVIG or other anti-inflammatory medications with the exception of NSAIDs Medical records indicate that child has genetic or other syndromes such as fragile X, neurofibromatosis, Rett syndrome, tuberous sclerosis, PTEN mutation, cerebral palsy, cystic fibrosis, muscular dystrophy, Crohn's disease, or rheumatoid disease Co-morbid condition that would influence child's performance on assessments. Central Nervous System (CNS) infection History of unstable epilepsy or uncontrolled seizure disorder, infantile spasms, Lennox Gastaut syndrome, Dravet syndrome Known pathogenic copy number variation (CNV) (e.g. 16p11.2, 15q13.2, 2q13.3) Significant sensory (i.e., deafness, blind) or motor impairment (CP) (if using Language Environment Analysis (LENA), no uncorrected hearing impairment) Presence of obvious physical dysmorphology Review of medical records indicates ASD diagnosis not likely or other serious complicating genetic or medical condition present Impaired renal or liver function as determined by serum creatinine >1.5mg/dL and/or total bilirubin>1.3mg/dL Clinically significant abnormalities in Complete Blood Count (CBC): Hemoglobin < 10.0 g/dL, White Blood Count (WBC) < 3.8 x 10e9, Platelets < 150x 10e9. Known metabolic disorder, mitochondrial dysfunction Uncontrolled infection, presence of or infection with HIV Active malignancy Macroencephaly or microencephaly ( >2 standard deviations in the relevant direction between head circumference and height) Change in current stable use of psychoactive medications; as per parent report.

Ages Eligible for Study
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Minimum Age: 24 Months
Maximum Age: 72 Months

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Autologous Umbilical Cord Blood (UCB)<br>All participants will receive a single intravenous (into the vein) infusion of autologous umbilical cord blood cells. | Biological: Autologous Umbilical Cord Blood<br>* All participants will receive autologous umbilical cord blood cells with a pre-cryopreservation cell dose of 1-5 x 10^7 Total Nucleated Cells (TNC)/kilogram of subject body weight. The cells will be administered as a single intravenous (into the vein) infusion over 2 to 25 minutes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with non-serious and serious adverse events. |  | up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary efficacy measure will be change in the Vineland Adaptive Behavior Scale- II |  | up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autism Spectrum Disorder, ASD, Umbilical cord blood, Autologous cord blood, cord blood