A Phase II Randomized Clinical Trial of the Safety and Efficacy of Intravenous Umbilical Cord Blood Infusion for Treatment of Children with Autism Spectrum Disorder.

Abstract

Objective

To evaluate whether umbilical cord blood (CB) infusion is safe and associated with improved social and communication abilities in children with autism spectrum disorder (ASD).

Study design

This prospective, randomized, placebo-controlled, double-blind study included 180 children with ASD, aged 2-7 years, who received a single intravenous autologous (n = 56) or allogeneic (n = 63) CB infusion vs placebo (n = 61) and were evaluated at 6 months postinfusion.

Results

CB infusion was safe and well tolerated. Analysis of the entire sample showed no evidence that CB was associated with improvements in the primary outcome, social communication (Vineland Adaptive Behavior Scales-3 [VABS-3] Socialization Domain), or the secondary outcomes, autism symptoms (Pervasive Developmental Disorder Behavior Inventory) and vocabulary (Expressive One-Word Picture Vocabulary Test). There was also no overall evidence of differential effects by type of CB infused. In a subanalysis of children without intellectual disability (ID), allogeneic, but not autologous, CB was associated with improvement in a larger percentage of children on the clinician-rated Clinical Global Impression-Improvement scale, but the OR for improvement was not significant. Children without ID treated with CB showed significant improvements in communication skills (VABS-3 Communication Domain), and exploratory measures including attention to toys and sustained attention (eye-tracking) and increased alpha and beta electroencephalographic power.

Conclusions

Overall, a single infusion of CB was not associated with improved socialization skills or reduced autism symptoms. More research is warranted to determine whether CB infusion is an effective treatment for some children with ASD.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1016/j.jpeds.2020.03.011

Publication Info

Dawson, Geraldine, Jessica M Sun, Jennifer Baker, Kimberly Carpenter, Scott Compton, Megan Deaver, Lauren Franz, Nicole Heilbron, et al. (2020). A Phase II Randomized Clinical Trial of the Safety and Efficacy of Intravenous Umbilical Cord Blood Infusion for Treatment of Children with Autism Spectrum Disorder. The Journal of pediatrics, 222. pp. 164–173.e5. 10.1016/j.jpeds.2020.03.011 Retrieved from https://hdl.handle.net/10161/24573.

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Scholars@Duke

Dawson

Geraldine Dawson

William Cleland Distinguished Professor

Geraldine Dawson is the William Cleland Distinguished Professor of Psychiatry and Behavioral Sciences at Duke University, where she also is a Professor of Pediatrics and Psychology & Neuroscience.  Dawson also is the Founding Director of the Duke Center for Autism and Brain Development, an NIH Autism Center of Excellence, which is an interdisciplinary research program and clinic, aimed to improve the lives of those diagnosed with autism through research, education, clinical services, and policy. Dawson received a Ph.D. in Developmental and Child Clinical Psychology from the University of Washington and completed a clinical internship at the UCLA Neuropsychiatric Institute.

Dawson's work focuses on improving methods for early detection and intervention for autism, understanding brain function in autism, and validation of autism EEG biomarkers. She co-developed the Early Start Denver Model, an empirically-validated early autism intervention that is used worldwide. She collaborates with colleagues in the departments of computer science and engineering, pediatrics, and biostatistics to develop novel digital health approaches to autism screening and outcome monitoring. 

Dawson previously served as Director of the Duke Institute for Brain Sciences, President of the International Society for Autism Research, and was appointed by the US Secretary of Health as a member of the NIH Interagency Autism Coordinating Committee (IACC) which develops the federal strategic plan for autism research, services, and policy. Dawson is a member of the American Academy of Arts and Sciences. She was Founding Director of the University of Washington (UW) Autism Center and the Duke Center for Autism and Brain Development. Dawson's awards include the American Psychological Association Distinguished Career Award (Div53); Association for Psychological Science Lifetime Achievement Award; Clarivate Top 1% Cited Researcher Across All Scientific Fields; among others. Dawson is a Fellow of the International Society for Autism Research, the American Psychological Society, and the American Psychological Association. 

Jessica Muller Sun

Assistant Professor of Pediatrics
Carpenter

Kimberly Carpenter

Assistant Professor in Psychiatry and Behavioral Sciences

Dr. Kimberly Carpenter is a clinical neuroscientist specializing in understanding complex brain-behavior relationships in young children with autism and associated disorders. Her program of research includes four interrelated research themes: (1) Understanding the impact of comorbid disorders on clinical and behavioral outcomes of young autistic children; (2) Identification of early risk factors for the development of psychiatric and neurodevelopmental disorders; (3) Identification of brain-based biomarkers for group stratification and treatment response tracking in young children; and (4) Improving methods for screening, early identification, and treatment monitoring in autism and associated disorders. She currently leads an innovative research program exploring the shared and unique impacts that co-occurring anxiety and ADHD have on brain and behavioral biomarkers in young autistic children. She was the first to demonstrate that sensory over-responsivity, a symptom that has been described as part of a number of disorders including autism, anxiety, and ADHD, is a specific and unidirectional risk factor for the development of anxiety disorders in young children. She was also the first to demonstrate that, when accounting for comorbidity among individual anxiety disorders, specific anxiety disorders are associated with phenotypically meaningful differences in brain connectivity using MRI. Dr. Carpenter has also collaborated with experts in early childhood mental health, computer science, and engineering to develop novel technologies that utilize multi-modal methods via computer vision and machine learning to develop, refine, and test novel screening tools for early identification and treatment monitoring in young children with autism and related disorders.

Franz

Lauren Franz

Associate Professor of Psychiatry and Behavioral Sciences

Dr Franz's research focuses on improving access to evidence-based services and support for neurodevelopmental disabilities, including autism, in diverse, low-resource, local and global communities.

Heilbron

Nicole Heilbron

Associate Professor in Psychiatry and Behavioral Sciences

Child clinical psychology, child and adolescent trauma and maltreatment, nonsuicidal self-injury (NSSI), suicide-related thoughts and behaviors, mood and anxiety disorders, OCD

Horrigan

Joseph Patrick Horrigan

Associate Consulting Professor in the Department of Psychiatry and Behavioral Sciences
Howard

Jill E. Howard

Assistant Professor in Psychiatry and Behavioral Sciences

Autism spectrum disorder diagnosis and treatment, infant-toddler risk and diagnosis, trajectories of early development

Prasad

Vinod K. Prasad

Consulting Professor in the Department of Pediatrics

1. Expanding the role of umbilical cord blood transplants for inherited metabolic disorders.
2. Impact of histocompatibility and other determinants of alloreactivity on clinical outcomes of unrelated cord blood transplants.
3. Studies to analyse the impact of Killer Immunoglobulin receptors on the outcomes of hematopoietic stem cell transplantation utilizing haploidentical, CD34 selected, familial grafts.
4. Propective longitudinal study of serial monitoring of adenovirus in allogenic transpants(SMAART)patients.
5. Use of mesenchymal stem cells for the treatment of GVHD

Song

Allen W Song

Professor in Radiology

The research in our lab is concerned with advancing structural and functional MRI methodologies (e.g. fast and high-resolution imaging techniques) for human brain imaging. We also aim to improve our understanding of functional brain signals, including spatiotemporal characterizations of the blood oxygenation level dependent contrast and alternative contrast mechanisms that are more directly linked to the neuronal activities. Additional effort is invested in applying and validating the developed methods to study human functional neuroanatomy.

Vermeer

Saritha Vermeer

Assistant Professor in Psychiatry and Behavioral Sciences
Troy

Jesse David Troy

Associate Professor of Biostatistics & Bioinformatics

I am the Associate Director of Graduate Studies for the Master of Biostatistics program. I am also an instructor in the Clinical Research Training Program. I work on research studies in cancer therapeutics and palliative care at the Duke Cancer Institute.

Kurtzberg

Joanne Kurtzberg

Jerome S. Harris Distinguished Professor of Pediatrics

Dr. Kurtzberg is an internationally renowned expert in pediatric hematology/oncology, pediatric blood and marrow transplantation, umbilical cord blood banking and transplantation, and novel applications of cord blood and birthing tissues in the emerging fields of cellular therapies and regenerative medicine.   Dr. Kurtzberg serves as the Director of the Marcus Center for Cellular Cures (MC3), Director of the Pediatric Transplant and Cellular Therapy Program, Director of the Carolinas Cord Blood Bank, and Co-Director of the Stem Cell Transplant Laboratory at Duke University.  The Carolinas Cord Blood Bank is an FDA licensed public cord blood bank distributing unrelated cord blood units for donors for hematopoietic stem cell transplantation (HSCT) through the CW Bill Young Cell Transplantation Program.  The Robertson GMP Cell Manufacturing Laboratory supports manufacturing of RETHYMIC (BLA, Enzyvant, 2021), allogeneic cord tissue derived and bone marrow derived mesenchymal stromal cells (MSCs), and DUOC, a microglial/macrophage cell derived from cord blood.

Dr. Kurtzberg’s research in MC3 focuses on translational studies from bench to bedside, seeking to develop transformative clinical therapies using cells, tissues, molecules, genes, and biomaterials to treat diseases and injuries that currently lack effective treatments. Recent areas of investigation in MC3 include clinical trials investigating the safety and efficacy of autologous and allogeneic cord blood in children with neonatal brain injury – hypoxic ischemic encephalopathy (HIE), cerebral palsy (CP), and autism. Clinical trials testing allogeneic cord blood are also being conducted in adults with acute ischemic stroke. Clinical trials optimizing manufacturing and testing the safety and efficacy of cord tissue MSCs in children with autism, CP and HIE and adults with COVID-lung disease are underway. DUOC, given intrathecally, is under study in children with leukodystrophies and adults with primary progressive multiple sclerosis.

In the past, Dr. Kurtzberg has developed novel chemotherapeutic drugs for acute leukemias, assays enumerating ALDH bright cells to predict cord blood unit potency, methods of cord blood expansion, potency assays for targeted cell and tissue based therapies. Dr. Kurtzberg currently holds several INDs for investigational clinical trials from the FDA.  She has also trained numerous medical students, residents, clinical and post-doctoral fellows over the course of her career.


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