Autologous Cord Blood Stem Cells for Autism

Study Overview
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Brief Summary
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Evaluate the efficacy of one infusion of stem cells from autologous umbilical cord blood in patients with autism over six months after infusion as measured by changes in expressive and receptive language. Also demonstrate improved behavior, learning, and changes in Serum tumor necrosis factor alpha (TNF-α), tumor necrosis factor beta (TNF-β), interleukin 1-alpha (IL-1α), interleukin 1-beta (IL-1β), interleukin 6 (IL-6), interleukin 10 (IL-10), and interleukin 13 (IL-13).

Detailed Description
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This is a single-center, randomized, placebo-controlled, crossover outpatient study with 15 subjects receiving one infusion of autologous umbilical cord blood (AUCB) containing a minimum of 10 million total nucleated cells per kilogram (TNC/kg) and 15 subjects receiving an infusion of placebo (saline). After the 24-week follow-up testing is conducted, the groups will crossover so that patients who initially received AUCB will receive placebo and patients who received placebo at baseline will receive the cord blood. Both groups will be tested again 24-weeks after infusion. The neuropsychologist, PI, staff from Cord Blood Registry (CBR), and parents will be blinded as to the infusion sequence. The duration of participation for each study subject is approximately 55 weeks. This includes one screening visit over a period of approximately 6 weeks, one visit for baseline testing, one day for infusion of TNC (minimum 10 million/kg) or saline placebo followed by 24 weeks of follow-up. A second baseline visit is conducted at week-24 with the second infusion of TNC or saline placebo occurring 5-7 days after. Twenty-four additional weeks of follow-up occur after the second infusion.

Official Title
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A Randomized, Blinded, Placebo-controlled, Crossover Study to Assess the Efficacy of Stem Cells From Autologous Umbilical Cord Blood to Improve Language and Behavior in Children With Autism

Conditions
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Autism

Intervention / Treatment
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* Biological: Autologous Cord Blood Stem Cells
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 2 to 7 years of age Diagnosis of Autistic Disorder as diagnosed by the Diagnostic and Statistical Manual, 4th Edition, Text Revision (DSM-IV-TR) developmental delays, and ADOS A sufficient quantity of autologous cord blood stored at Cord Blood Registry that was stored and processed using the Thermogenesis AutoXpress Platform Stable on any current medications for at least 2 months prior to infusion of cord blood Medical records indicating that patient does not have genetic conditions such as cerebral palsy, cystic fibrosis, muscular dystrophy, crohns disease, rheumatoid disease, fragile X, Retts Syndrome, Angelman Syndrome, tuberous sclerosis, epilepsy, or known genetic defects that overlap autism spectrum. Results of an EEG within 12-months of baseline English speaking Exclusion Criteria: CNS infection Extreme prematurity (< 34 weeks gestation) Severe Cognitive Disability IQ below 45 with autism Clinical seizure activity within 6 months of baseline Lennox Gastaut syndrome or infantile spasms Dravet syndrome HIV, renal or hepatic impairment Prior hematological or malignant disease Fever of 101 F within 2 weeks prior to infusion Serious CNS infection or trauma Unwilling to commit to follow-up Mental illness including schizophrenia Pervasive Developmental Disorder-Not Otherwise Specified Asperger's Disorder Cord blood unit is less than 85% viable, has a TNC of less than 10 million/kg, or sterility testing results are positive Garlic allergy Previous adverse reaction to Dimethyl Sulfoxide (DMSO) Maternal medical records indicate communicable diseases including HIV, Hepatitis B or C, syphilis, cytomegalovirus (CMV) Currently taking anti-inflammatory medications History of asthma who may potentially require treatment with steroids Inflammatory Disease Renal/hepatic disease: serum Creatinine > 1.5 mg/dl and total Bilirubin > 1.5 mg/dl Allergic to diphenhydramine (Benadryl) Treatment with chelation therapy, hyperbaric oxygen therapy, pig worm therapy, or other alternative therapies the investigator deems clinically relevant

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 7 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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Autologous Cord Blood Stem Cells<br> | Biological: Autologous Cord Blood Stem Cells<br>* One infusion of 60 ml syringe of study product<br>|
| Placebo Comparator: Placebo<br>Saline | Biological: Placebo<br>* Saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Language (Total Standard Score, Range 40 - 160) | Change in language as measured by the Receptive One-Word Vocabulary Test (ROWVT-4) and Expressive One-Word Vocabulary Test (EOWVT-4) at baseline and six months following infusion of stem cells from AUCB or infusion of placebo. The ROWPVT-4 and EOWPVT-4 were administered by a neuropsychologist and are norm-referenced assessments. The ROWPVT-4 tests an individual's ability to match a spoken word with an image of an object, action, or concept. The EOWPVT-4 tests an individual's ability to name, with one word, objects, actions, and concepts when presented with color illustrations. The tests target the ability to understand the meaning of words spoken and name what is depicted on a test plate without context. Scores of 85-115 are considered to be within the average range of functioning. | Baseline and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Behavior/Learning (Standard Score, Range 40 - 160 for Each Subtest) | Change in the Vineland Adaptive Behavior and Socialization Scales (2nd edition) between baseline and six months after infusion of AUCB containing stem cells. Vineland Adaptive Behavior and Socialization Scales consist of the following subparts: Daily Living Skills, Socialization, and Adaptive Behavior Composite (ABC). These are questionnaires completed by a parent or caregiver. Scores above 80 are classified using approximately the same ranges as IQ tests. Scores below 80 are categorized as borderline adaptive functioning (70-80); mildly deficient adaptive functioning (51-69); moderately deficient adaptive behavior (36-50); severely deficient adaptive behavior; (20-35); and markedly or profoundly deficient adaptive behavior (<20). | Baseline and 6 months | 
| Change in Knowledge and Fluid Reasoning (Scaled Score, Range 1-19 for Each Subtest) | The Stanford Binet, version 5, was used to assess the brain function. It can assess the level of intelligence across several age spans and ability levels. The Stanford-Binet looks at intelligence in five areas. In this study 2 areas were looked at: Knowledge and Fluid Reasoning that were age and condition appropriate. Each sub-test has a mean of 10 and a standard deviation of 3. The standard deviation indicates how far above or below the norm the subject's score is. Scores of 7 to 13 are considered to be within the average range of functioning. | Baseline and 6 months |