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

NCT ID: NCT02176317

Last Updated: 2019-12-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-06-30
• Study Completion Date: 2015-12-31

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.

Conditions

Autism Spectrum Disorder

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Autologous Umbilical Cord Blood (UCB)

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

Group Type: EXPERIMENTAL

Autologous Umbilical Cord Blood

Intervention Type: BIOLOGICAL

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

Interventions

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

Intervention Type: BIOLOGICAL

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.

• Minimum Eligible Age: 24 Months
• Maximum Eligible Age: 72 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Marcus Foundation

OTHER

Sponsor Role: collaborator

PerkinElmer, Inc.

INDUSTRY

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Joanne Kurtzberg, MD

Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Joanne Kurtzberg, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

Duke University Medical Center

Durham, North Carolina, United States

Countries

United States

References

Simhal AK, Carpenter KLH, Nadeem S, Kurtzberg J, Song A, Tannenbaum A, Sapiro G, Dawson G. Measuring robustness of brain networks in autism spectrum disorder with Ricci curvature. Sci Rep. 2020 Jul 2;10(1):10819. doi: 10.1038/s41598-020-67474-9.

Reference Type: DERIVED

PMID: 32616759 (View on PubMed)

Other Identifiers

Pro00052449

Identifier Type: -

Identifier Source: org_study_id