Autism Spectrum Disorder
Conditions
Keywords
Autism Spectrum Disorder, ASD, Umbilical cord blood, Autologous cord blood, cord blood
Brief summary
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
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.
Interventions
BIOLOGICALAutologous Umbilical Cord Blood
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
Sponsors
The Marcus Foundation
PerkinElmer, Inc.
Duke University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
24 Months to 72 Months
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 24 months to ≤72months at the time of visit 1 2. 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 3. IQ ≥ 35 on Stanford Binet Intelligence Scale or similar standardized test 4. 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 5. Stable on current medications for at least 2 months prior to infusion of cord blood 6. 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 7. Parental consent 8. Subject and parent/guardian must be English speaking
Exclusion criteria
1. Unwilling to commit to follow up for a year 2. History of prior cell therapy 3. Use of IVIG or other anti-inflammatory medications with the exception of NSAIDs 4. 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 5. Co-morbid condition that would influence child's performance on assessments. 6. Central Nervous System (CNS) infection 7. History of unstable epilepsy or uncontrolled seizure disorder, infantile spasms, Lennox Gastaut syndrome, Dravet syndrome 8. Known pathogenic copy number variation (CNV) (e.g. 16p11.2, 15q13.2, 2q13.3) 9. Significant sensory (i.e., deafness, blind) or motor impairment (CP) (if using Language Environment Analysis (LENA), no uncorrected hearing impairment) 10. Presence of obvious physical dysmorphology 11. Review of medical records indicates ASD diagnosis not likely or other serious complicating genetic or medical condition present 12. Impaired renal or liver function as determined by serum creatinine \>1.5mg/dL and/or total bilirubin\>1.3mg/dL 13. Clinically significant abnormalities in Complete Blood Count (CBC): Hemoglobin \< 10.0 g/dL, White Blood Count (WBC) \< 3.8 x 10e9, Platelets \< 150x 10e9. 14. Known metabolic disorder, mitochondrial dysfunction 15. Uncontrolled infection, presence of or infection with HIV 16. Active malignancy 17. Macroencephaly or microencephaly ( \>2 standard deviations in the relevant direction between head circumference and height) 18. Change in current stable use of psychoactive medications; as per parent report.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of participants with non-serious and serious adverse events. | up to 12 months |
Secondary
| Measure | Time frame |
|---|---|
| The primary efficacy measure will be change in the Vineland Adaptive Behavior Scale- II | up to 12 months |
Other
| Measure | Time frame |
|---|---|
| Change in Sensory Experience Questionnaire | up to 12 months |
| Change in Behavior Assessment of Children | up to 12 months |
| Change in Autism Diagnostic Observation Scale | up to 12 months |
| Change in Clinical Global Impression- Severity and Improvement Scales | up to 12 months |
| Change in Stanford Binet Intelligence Scale or other standardized IQ test | up to 12 months |
| Change in frequency of child vocalization/ conversational turns | up to 12 months |
| Change in Pervasive Developmental Disorder- Behavior Inventory | up to 12 months |
| Change in Preschool Age Psychiatric Assessment | up to 12 months |
| Change in Aberrant Behavior Checklist | up to 12 months |
| Prevalent and incident of GI symptoms | up to 12 months |
| Change in Parenting Stress Index | up to 12 months |
| Change in attention to social stimuli assessed via eye-tracking and electroencephalography (EEG) | up to 12 months |
| Change in Expressive One-Word Picture Vocabulary Test | up to 12 months |
| Change in Repetitive Behavior Scal | up to 12 months |
Countries
United States
Outcome results
None listed