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Cord Blood Infusion for Children With Autism Spectrum Disorder (Duke ACT)

This study is enrolling participants by invitation only.
Sponsor:
Information provided by (Responsible Party):
Joanne Kurtzberg, MD, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT02847182
First received: July 25, 2016
Last updated: April 5, 2017
Last verified: April 2017
  Purpose
This is a single site, prospective, randomized, double-blind study of a single intravenous autologous or allogeneic, unrelated cord blood (CB) infusion in children ages 2-7 years with Autism Spectrum Disorder (ASD). Participants will be randomly assigned to Sequence A, consisting of a single infusion of CB cells at baseline followed 6 months later by a single infusion of placebo, or Sequence B, consisting of an infusion of placebo at baseline followed 6 months later by an infusion of CB cells. All participants will ultimately be treated with CB cells at some point during the study. Participants with an available qualified autologous CB unit will receive autologous cells, and those without a suitable autologous CB unit available will receive cells from a ≥4/6 HLA-matched, ABO-matched allogeneic, unrelated donor CB unit from the Carolinas Cord Blood Bank. All infusions will be double-blinded. The primary outcomes will be assessed 6 months after the initial infusion in the sequence. Additional testing for secondary exploratory analyses will be performed at 12 months. Duration of study participation will be 12 months from the time of baseline infusion.

Condition Intervention Phase
Autism Spectrum Disorder
ASD
Autism
PDD
Biological: Cord Blood Infusion
Biological: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Primary Purpose: Treatment
Official Title: Efficacy of Intravenous Umbilical Cord Blood Infusion as Cell Therapy for Children With Autism Spectrum Disorder (ASD): Duke ACT

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Change in social communication [ Time Frame: Baseline, 6 months ]
    The primary endpoint of this study is the change in social communication skills (a core symptom of autism) from baseline to six months after the initial study infusion, as measured by the Vineland Adaptive Behavior Scale (VABS)-II Survey Interview Form, Socializations Subscale Standard Score. Control (placebo) and treated patients will be compared.


Secondary Outcome Measures:
  • Change in Vineland Socialization domain raw score [ Time Frame: Baseline, 6 months ]
  • Change in Vineland Socialization domain age equivalent [ Time Frame: Baseline, 6 months ]
  • Change in Pervasive Developmental Disorder Behavior Inventory (PDD-BI) composite standard score (parent questionnaire) [ Time Frame: Baseline, 6 months ]
  • Change in CGI-S (clinician assessment) [ Time Frame: Baseline, 6 months ]
  • Change in CGI-I (clinician assessment) [ Time Frame: Baseline, 6 months ]
  • Change in Expressive One-Word Picture Vocabulary Test (clinician assessment) [ Time Frame: Baseline, 6 months ]
  • Change in Vineland Adaptive Behavior Communication subscale standard score [ Time Frame: Baseline, 6 months ]
  • Change in Vineland Adaptive Behavior Daily Living subscale standard score [ Time Frame: Baseline, 6 months ]
  • Change in Vineland Adaptive Behavior Composite [ Time Frame: Baseline, 6 months ]
  • Change in individual subscales of the PDD-BI t scores [ Time Frame: Baseline, 6 months ]
  • Incidence of infusion reactions [ Time Frame: 12 months ]
  • Severity of infusion reactions [ Time Frame: 12 months ]
    Grade/severity will be assessed according to CTCAE v4.0 guidelines

  • Incidence of product-related infections [ Time Frame: 12 months ]
  • Severity of product-related infections [ Time Frame: 12 months ]
    Grade/severity will be assessed according to CTCAE v4.0 guidelines

  • Evidence of alloimmunization via anti-HLA and anti-RBC antibodies and nonspecific markers of systemic inflammation (ESR, CRP) [ Time Frame: 12 months ]
  • Incidence of graft vs. host disease [ Time Frame: 12 months ]
  • Severity of graft vs. host disease [ Time Frame: 12 months ]
    Grade/severity will be assessed according to CTCAE v4.0 guidelines

  • Incidence of unexpected adverse events, by relation to study product [ Time Frame: 12 months ]
  • Severity of unexpected adverse events, by relation to study product [ Time Frame: 12 months ]
    Grade/severity will be assessed according to CTCAE v4.0 guidelines


Estimated Enrollment: 165
Study Start Date: August 2016
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cord Blood Infusion (best source)
Subjects will be randomized to receive a cord blood infusion at the baseline or 6 month visit. The cord blood will be autologous (if available) or unrelated cord blood.
Biological: Cord Blood Infusion Biological: Placebo
Placebo Comparator: Placebo Infusion
Subjects will be randomized to receive a cord blood infusion at the baseline or 6 month visit or placebo. The cord blood will be autologous (if available) or unrelated cord blood. The placebo is an acellular media product similar in both appearance and odor.
Biological: Cord Blood Infusion Biological: Placebo

  Eligibility

Ages Eligible for Study:   2 Years to 7 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥ 2 years to ≤ 7 years (7 years, 364 days) at the time of visit 1
  2. Confirmed clinical DSM-5 diagnosis of Autism Spectrum Disorder using the DSM-5 Checklist
  3. Fragile X testing performed and negative
  4. Available and qualified umbilical cord blood unit with a minimum banked total nucleated cell dose of ≥ 2.5 x 107 cells/kg that meets criteria outlined in Section 6.0, either:

    • Autologous umbilical cord blood unit OR
    • ≥4/6 HLA-matched and ABO/Rh-matched allogeneic unrelated umbilical cord blood unit from the Carolinas Cord Blood Bank
  5. Stable on current psychiatric medication regimen (dose and dosing schedule) for at least 2 months prior to infusion of study product
  6. Normal absolute lymphocyte count (≥1500/uL)
  7. Participant and parent/guardian are English speaking
  8. Able to travel to Duke University two times (baseline and 6 months post-baseline), and parent/guardian is able to participate in interim surveys and interviews
  9. Parental consent

Exclusion Criteria:

  1. General:

    • Review of medical records indicates ASD diagnosis not likely
    • Known diagnosis of any of the following coexisting psychiatric conditions: depression, bipolar disorder, schizophrenia, obsessive compulsive disorder, Tourette syndrome
    • Screening data suggests that participant would not be able to comply with the requirements of the study procedures, including study outcome measures, as assessed by the study team
    • Family is unwilling or unable to commit to participation in all study-related assessments, including follow up for approximately 12 months
    • Sibling is enrolled in this (DukeACT) study
  2. Genetic:

    • Records indicate that child has a known genetic syndrome such as (but not limited to) Fragile X syndrome, neurofibromatosis, Rett syndrome, tuberous sclerosis, PTEN mutation, cystic fibrosis, muscular dystrophy b. Known pathogenic copy number variation (CNV) associated with ASD (e.g., 16p11.2, 15q13.2, 2q13.3)
  3. Infectious:

    • Known active central nervous system infection
    • Evidence of uncontrolled infection based on records or clinical assessment
    • HIV positivity
  4. Medical:

    • Known metabolic disorder
    • Known mitochondrial dysfunction
    • History of unstable epilepsy or uncontrolled seizure disorder, infantile spasms, Lennox Gastaut syndrome, Dravet syndrome, or other similar chronic seizure disorder
    • Active malignancy or prior malignancy that was treated with chemotherapy
    • History of a primary immunodeficiency disorder
    • History of autoimmune cytopenias (i.e., ITP, AIHA)
    • Coexisting medical condition thatwould place the child at increased risk for complications of sedation or other study procedures
    • Concurrent genetic or acquired disease or comorbidity(ies) that could require a future stem cell transplant
    • Significant sensory (e.g., blindness, deafness, uncorrected hearing impairment) or motor (e.g., cerebral palsy) impairment
    • Impaired renal or liver function as determined by serum creatinine >1.5mg/dL or total bilirubin >1.3mg/dL, except in patients with known Gilbert's disease
    • Significant hematologic abnormalities defined as: Hemoglobin <10.0 g/dL, White blood count < 3,000 cells/mL, absolute lymphocyte count <1000/uL, Platelets <150 x 10e9/uL
    • Evidence of clinically relevant physical dysmorphology indicative of a genetic syndrome as assessed by the PIs or other investigators, including a medical geneticist or psychiatrists trained in identifying dysmorphic features associated with neurodevelopmental conditions
  5. Current/Prior Therapy:

    • History of prior cell therapy
    • Current or prior use of immune globulins or other anti-inflammatory medications with the exception of non steroidal anti-inflammatory medications
    • Current or prior immunosuppressive therapy
    • No systemic steroid therapy that has lasted >2 weeks, and no systemic steroids within 3 months prior to enrollment. Topical and inhaled steroids are permitted.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02847182

Locations
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27705
Sponsors and Collaborators
Joanne Kurtzberg, MD
Investigators
Principal Investigator: Joanne Kurtzberg, MD Duke Medicine
  More Information

Responsible Party: Joanne Kurtzberg, MD, Chief Scientific Officer, Robertson Clinical and Translational Cell Therapy Program; Director, Pediatric Blood and Marrow Transplant Program and Carolinas Cord Blood Bank, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT02847182     History of Changes
Other Study ID Numbers: Pro00070514
Study First Received: July 25, 2016
Last Updated: April 5, 2017

Additional relevant MeSH terms:
Disease
Autistic Disorder
Autism Spectrum Disorder
Child Development Disorders, Pervasive
Pathologic Processes
Neurodevelopmental Disorders
Mental Disorders

ClinicalTrials.gov processed this record on April 24, 2017