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Open Label Phase I hCT-MSC in Toddlers With Autism Spectrum Disorder (TACT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04294290
Recruitment Status : Not yet recruiting
First Posted : March 4, 2020
Last Update Posted : July 1, 2020
Sponsor:
Collaborator:
The Marcus Foundation
Information provided by (Responsible Party):
Joanne Kurtzberg, MD, Duke University

Brief Summary:
This is a single site, prospective study of one intravenous infusion of human umbilical cord tissue-derived mesenchymal stromal cells (hCT-MSC) in toddlers with autism spectrum disorder (ASD). Toddlers 18 to 30 months of age with a confirmed diagnosis of ASD will be eligible to participate. Diagnosis will be confirmed at the time of the eligibility visit at the Duke Center for Autism and Brain Development. All participants will receive a single intravenous dose of 2x106/kg hCT-MSC per kilogram at baseline. Assessments will be conducted at baseline and 6 months, with remote follow-up assessments at 12 months.

Condition or disease Intervention/treatment Phase
Autism Spectrum Disorder Biological: hCT-MSC infusion Phase 1

Detailed Description:

The primary purpose of this study is to evaluate safety and feasibility. Safety assessments include monitoring of acute infusion reactions, adverse events, incidence of infections, and markers of alloimmunization. Clinical outcome measures will also be described. A key clinical outcome measeure is the change in social communication abilities from baseline to 6 months based on the Joint Engagement Rating Inventory (JERI), a commonly-used and well-validated coding system for rating the quality and quantity of social communication skills in toddlers with and without ASD.91 JERI coding rates social communication abilities on a 1 to 7 scale and factors in both the quantity and quality of skills. The total joint engagement score as well as ratings on all JERI subscales that comprise the total score will be described.

Other clinical endpoints will include the PDD Behavior Inventory (PDDBI) autism composite score, the mean of the Socialization Subscale Standard Score and Communication Subscale Standard Score on the Vineland Adaptive Behavior Scales (VABS-3), the Clinical Global Impression Scale (CGI) - Severity and Improvement Scales, the Communicative Development Inventories (CDI-2): Words & Sentences subscales, attention abilities via eye-tracking, and brain activity.

Exploratory clinical endpoints will include autism symptoms measured by an app that elicits and records autism symptoms on an iPad (SenseToKnow), Autism Diagnostic Observation Scale (ADOS-2) Calibrated Severity Score (overall, social affect, and repetitive behavior), PDD Behavior Inventory (PDDBI) Subscales, and VABS-3 Standard Score and age equivalent for the following subscales: Socialization, Communication, and Daily Living and the Standard Score and age equivalent for the VABS-3 Adaptive Behavior Composite.

Safety and VABS-3 assessments will also be conducted remotely at three and 12 months. Duration of study participation will be 12 months from the time of the baseline infusion.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: AN OPEN LABEL PHASE I STUDY OF hCT-MSC, AN UMBILICAL CORD-DERIVED MESENCHYMAL STROMAL CELL PRODUCT IN YOUNG CHILDREN WITH AUTISM SPECTRUM DISORDER
Estimated Study Start Date : August 1, 2020
Estimated Primary Completion Date : October 1, 2022
Estimated Study Completion Date : October 1, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: hCT-MSC infusion Biological: hCT-MSC infusion
This is a single site, phase I, open-label, prospective study of one intravenous infusion of human umbilical cord tissue-derived mesenchymal stromal cells (hCT-MSC) in 12 toddlers 18 to 30 months of age with autism spectrum disorder (ASD).




Primary Outcome Measures :
  1. Safety of hCT-MSC infusion as measured by incidence of infusion reactions [ Time Frame: 1 year ]
  2. Safety of hCT-MSC infusion as measured by severity of infusion reactions [ Time Frame: 1 year ]
    CTCAE is used to measure severity

  3. Safety of hCT-MSC infusion as measured by incidence of product-related infections [ Time Frame: 1 year ]
  4. Safety of hCT-MSC infusion as measured by severity of product-related infections [ Time Frame: 1 year ]
    CTCAE is used to measure severity

  5. Safety of hCT-MSC infusion as measured by evidence of alloimmunization via anit-HLA antibodies [ Time Frame: 1 year ]
  6. Safety of hCT-MSC infusion as measured by incidence of graft vs. host disease [ Time Frame: 1 year ]
  7. Safety of hCT-MSC infusion as measured by severity of graft vs. host disease [ Time Frame: 1 year ]
    CTCAE is used to measure severity

  8. Safety of hCT-MSC infusion as measured by incidence of unexpected adverse events [ Time Frame: 1 year ]
  9. Safety of hCT-MSC infusion as measured by severity of unexpected adverse events [ Time Frame: 1 year ]
    CTCAE is used to measure severity

  10. Change in PDD Behavior Inventory Autism Composite Score (PDDBI) [ Time Frame: Baseline, 6 months ]
  11. Change in mean of the Socialization Subscale and Communication Subscale standard scores on the Vineland Adaptive Behavior Scales (VABS-3) [ Time Frame: baseline, 6 months ]
  12. Change in Clinical Global Impression Scale (CGI) [ Time Frame: baseline, 6 months ]
  13. Change in Communicative Development Inventories (CDI-2) [ Time Frame: baseline, 6 months ]
  14. Change in attention abilities as assess via eye-tracking [ Time Frame: baseline, 6 months ]
  15. Change in brain activity as measured by EEG [ Time Frame: baseline, 6 months ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Months to 30 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥ 18 months to ≤ 30 months (30 months, 29 days) at the time of consent
  2. Confirmed clinical DSM-5 diagnosis of Autism Spectrum Disorder using the DSM-5 Checklist as informed by the Autism Diagnostic Observation Schedule - 2.
  3. Fragile X testing performed and negative; CMA and/or whole exome sequencing performed and results not linked to autism diagnosis
  4. Stable on current psychoactive medication regimen (dose and dosing schedule) for at least 2 months prior to infusion of study product
  5. Normal absolute lymphocyte count (≥1500/uL)
  6. Participant and parent/guardian are English speaking
  7. Able to travel to Duke University for two multi-day visits (baseline and six months) and parent/guardian is able to participate in interim surveys and interviews
  8. Parental consent

Exclusion Criteria:

  1. General:

    1. Review of medical records indicates ASD diagnosis not likely
    2. Screening data suggests that participant would not be able to comply with the requirements of the study procedures as assessed by the study team
    3. Family is unwilling or unable to commit to participation in all study-related assessments, including protocol follow up
    4. Sibling is enrolled in this (Duke hCT-MSC) study
  2. Genetic:

    1. 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 or a genetic mutation known to be associated with ASD
    2. Known pathogenic mutation or copy number variation (CNV) associated with ASD (e.g., 16p11.2, 15q13.2, 2q13.3)
  3. Infectious:

    1. Known active CNS infection
    2. Evidence of uncontrolled infection based on records or clinical assessment
    3. Known HIV positivity
  4. Medical:

    1. Known metabolic disorder
    2. Known mitochondrial dysfunction
    3. History of unstable epilepsy or uncontrolled seizure disorder, infantile spasms, Lennox Gastaut syndrome, Dravet syndrome, or other similar chronic seizure disorder
    4. Active malignancy or prior malignancy that was treated with chemotherapy
    5. History of a primary immunodeficiency disorder
    6. History of autoimmune cytopenias (i.e., ITP, AIHA)
    7. Coexisting medical condition that would place the child at increased risk for complications of study procedures
    8. Concurrent genetic or acquired disease or comorbidity(ies) that could require a future stem cell transplant
    9. Significant sensory (e.g., blindness, deafness, uncorrected hearing impairment) or motor (e.g., cerebral palsy) impairment
    10. 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
    11. Significant hematologic abnormalities defined as: Hemoglobin <10.0 g/dL, WBC < 3,000 cells/mL, ALC <1000/uL, Platelets <150 x 10e9/uL
    12. Known clinically relevant physical dysmorphology associated with neurodevelopmental conditions.
  5. Current/Prior Therapy:

    a. History of prior cell therapy b. Current or prior use of IVIG or other anti-inflammatory medications with the exception of NSAIDs c. Current or prior immunosuppressive therapy i. 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04294290


Contacts
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Contact: Bethany Kistler, RN 9196681102 cordbloodtherapyinfo@dm.duke.edu
Contact: Lauren Driggers-Jones, PhD cordbloodtherapyinfo@dm.duke.edu

Sponsors and Collaborators
Duke University
The Marcus Foundation
Investigators
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Principal Investigator: Joanne Kurtzberg, MD Duke Health
Principal Investigator: Geraldine Dawson, PhD Duke Health
Principal Investigator: Jessica Sun, MD Duke Health
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Responsible Party: Joanne Kurtzberg, MD, Jerome Harris Distinguished Professor of Pediatrics, Duke University
ClinicalTrials.gov Identifier: NCT04294290    
Other Study ID Numbers: Pro00104460
First Posted: March 4, 2020    Key Record Dates
Last Update Posted: July 1, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Joanne Kurtzberg, MD, Duke University:
Autism Spectrum Disorder
ASD
Autism
PDD
Additional relevant MeSH terms:
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Disease
Autistic Disorder
Autism Spectrum Disorder
Child Development Disorders, Pervasive
Pathologic Processes
Neurodevelopmental Disorders
Mental Disorders