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

• Sponsor: Duke University
• Collaborators: The Marcus Foundation; PerkinElmer, Inc.
• Information provided by (Responsible Party): Joanne Kurtzberg, MD, Duke University

Tracking Information

• First Submitted Date: June 16, 2014
• First Posted Date: June 27, 2014
• Last Update Posted Date: June 7, 2019
• Study Start Date: June 2014
• Actual Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 26, 2014): Number of participants with non-serious and serious adverse events. [ Time Frame: up to 12 months ]
• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT02176317 on ClinicalTrials.gov Archive Site
• Current Secondary Outcome Measures (submitted: June 26, 2014): The primary efficacy measure will be change in the Vineland Adaptive Behavior Scale- II [ Time Frame: up to 12 months ]
• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: June 26, 2014)

• Change in Pervasive Developmental Disorder- Behavior Inventory [ Time Frame: up to 12 months ]
• Change in Repetitive Behavior Scal [ Time Frame: up to 12 months ]
• Change in Sensory Experience Questionnaire [ Time Frame: up to 12 months ]
• Change in Behavior Assessment of Children [ Time Frame: up to 12 months ]
• Change in Autism Diagnostic Observation Scale [ Time Frame: up to 12 months ]
• Change in Clinical Global Impression- Severity and Improvement Scales [ Time Frame: up to 12 months ]
• Change in Stanford Binet Intelligence Scale or other standardized IQ test [ Time Frame: up to 12 months ]
• Change in frequency of child vocalization/ conversational turns [ Time Frame: up to 12 months ]
• Change in Expressive One-Word Picture Vocabulary Test [ Time Frame: up to 12 months ]
• Change in Preschool Age Psychiatric Assessment [ Time Frame: up to 12 months ]
• Change in Aberrant Behavior Checklist [ Time Frame: up to 12 months ]
• Prevalent and incident of GI symptoms [ Time Frame: up to 12 months ]
• Change in Parenting Stress Index [ Time Frame: up to 12 months ]
• Change in attention to social stimuli assessed via eye-tracking and electroencephalography (EEG) [ Time Frame: up to 12 months ]

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Autologous Umbilical Cord Blood Infusion for Children With Autism Spectrum Disorder (ASD)
• Official Title: Autologous Umbilical Cord Blood Infusion for Children With Autism Spectrum Disorder (ASD)
• 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.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Autism Spectrum Disorder

Intervention

Biological: Autologous 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

Study Arms

Experimental: Autologous Umbilical Cord Blood (UCB)

All participants will receive a single intravenous (into the vein) infusion of autologous umbilical cord blood cells.

Intervention: Biological: Autologous Umbilical Cord Blood

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 12, 2015): 25
• Original Estimated Enrollment (submitted: June 26, 2014): 20
• Actual Study Completion Date: December 2015
• Actual Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 24 Months to 72 Months (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02176317
• Other Study ID Numbers: Pro00052449
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Joanne Kurtzberg, MD, Duke University
• Study Sponsor: Duke University

Collaborators

• The Marcus Foundation
• PerkinElmer, Inc.

Investigators

• Principal Investigator: Joanne Kurtzberg, MD; Duke University

• PRS Account: Duke University
• Verification Date: June 2019