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Safety Study of Autologous Umbilical Cord Blood Cells for Treatment of Hypoplastic Left Heart Syndrome

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01883076
Recruitment Status : Completed
First Posted : June 21, 2013
Last Update Posted : April 29, 2022
Sponsor:
Collaborators:
University of Oklahoma
Children's Hospital of Philadelphia
Children's Hospitals and Clinics of Minnesota
Children's Hospital Los Angeles
Children's Hospital Colorado
Mayo Clinic
Information provided by (Responsible Party):
Timothy J Nelson, MD, PhD, ReGen Theranostics, Inc.

Study Description
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Brief Summary:

This is a Phase I study to determine the safety and feasibility of injections of autologous umbilical cord blood (UCB) cells into the right ventricle of Hypoplastic Left Heart Syndrome (HLHS) children undergoing a scheduled Glenn surgical procedure.

The investigators are doing this research study to find out if autologous stem cells from the individual's own umbilical cord blood can be used to strengthen the muscle of the right side of their heart. This will help determine the safety and feasibility of using cell-based regenerative therapy as an additional treatment for the management of HLHS.


Condition or disease Intervention/treatment Phase
Hypoplastic Left Heart Syndrome Biological: autologous cell-based delivery Phase 1

Detailed Description:
This study is a Phase I trial to determine the safety of autologous mononuclear cells (MNC) derived from umbilical cord blood for intramyocardial delivery into the right ventricle during a planned and non-emergent Stage II surgical palliation in subjects with HLHS. This is the first critical step towards applying autologous MNC therapy as an add-on regenerative intervention for congenital heart disease management. The choice of HLHS as the target disease for regenerative therapies in congenital heart disease management is multi-factorial and includes the following considerations: 1) Severity of of this incurable disease, 2) palliative nature and burden of long-term outcomes with a single right ventricular system, 3) three stages of planned surgical procedures that provide time points to adjunctively intervene, and 4) prenatal diagnosis enabling planned collection of UCB. An emerging goal for cardiac regeneration includes the application of cell-based technology to congenital heart disease, which is a favorable substrate due to the lack of fibrotic scaring, and the presence of a microenvironment that is expected to support ongoing cardiac proliferation and growth for functional remuscularization. This Phase I safety study will determine the feasibility of collection, processing, and delivery of autologous cells as used in adult cardiac regenerative protocols in the setting of HLHS surgical management.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Safety Study of Autologous Umbilical Cord Blood Derived Mononuclear Cells During Surgical Stage II Palliation of Hypoplastic Left Heart Syndrome
Actual Study Start Date : May 15, 2013
Actual Primary Completion Date : April 28, 2021
Actual Study Completion Date : April 28, 2021

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: autologous cell-based delivery
autologous cell-based delivery a target dose of 3 million cells / kg of body weight will be delivered into the right heart muscle at the time of surgery. Cells are derived from autologous (self) umbilical cord blood.
 Biological: autologous cell-based delivery
autologous cells (derived from "self")
Other Name: umbilical cord blood derived mononuclear cells


Outcome Measures
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Primary Outcome Measures :
  1. Incidence of all-cause mortality [ Time Frame: Within 2 years following cell therapy treatment ]
  2. Incidence of new and worsening adverse cardiac events [ Time Frame: Within 2 years following cell therapy treatment ]
    The adverse cardiac events would include sustained/symptomatic ventricular arrhythmias, heart failure, myocardial infarction, cardiac infections, and unexpected cardiovascular surgery.

  3. Percentage of subjects whose cells meet all cell release criteria [ Time Frame: Up to 2 years ]
  4. Percentage of subjects enrolled who undergo cell therapy treatment [ Time Frame: Up to 2 years ]

Secondary Outcome Measures :
  1. Change in right ventricular ejection fraction at one month according to cardiac imaging with echocardiography [ Time Frame: baseline, 1 month ]
  2. Change in right ventricular ejection fraction at 3 months according to cardiac imaging with echocardiography [ Time Frame: baseline, 3 months ]
  3. Change in right ventricular ejection fraction at 6 months according to cardiac imaging with echocardiography [ Time Frame: baseline, 6 months ]
  4. Change in right ventricle tricuspid annular plane systolic excursion (TAPSE) at one month according to cardiac imaging with echocardiography [ Time Frame: baseline, 1 month ]
  5. Change in right ventricle TAPSE at 3 months according to cardiac imaging with echocardiography [ Time Frame: baseline, 3 months ]
  6. Change in right ventricle TAPSE at 6 months according to cardiac imaging with echocardiography [ Time Frame: baseline, 6 months ]
  7. Change in right ventricle fractional area change at one month according to cardiac imaging with echocardiography [ Time Frame: baseline, 1 month ]
  8. Change in right ventricle fractional area change at 3 months according to cardiac imaging with echocardiography [ Time Frame: baseline, 3 months ]
  9. Change in right ventricle fractional area change at 6 months according to cardiac imaging with echocardiography [ Time Frame: baseline, 6 months ]

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

Inclusion Criteria

  1. Individuals with autologous cord blood product that met all cell release criteria (listed on the certificate of analysis from Mayo Clinic Human Cell Therapy Lab) as follows:

    1. No aerobic or anaerobic bacterial growth after 14 days
    2. Greater than 70% cell viability pre-freeze
    3. Total Nucleated Cells (TNC) concentration of 30-42 x 106 cells/mL (pre-freeze)
    4. Minimum of one (1) vial of cells
    5. Mononuclear cell percentage of greater than 50%
    6. Endotoxin result of less than 16 Endotoxin Units (EU)/mL.
  2. Mother's serology test results are negative for HIV, Hepatitis B, and Hepatitis C.
  3. Individuals with HLHS having undergone Stage I surgical palliation and undergoing planned Stage II palliative Glenn surgery.
  4. Ages up to 18 months are eligible if written informed consent can be obtained from both parents (unless one parent is not reasonably available) and/or legal guardians.

Exclusion Criteria

  1. Child who's UCB does not meet the specified cell release criteria in Inclusion Criterion #1.
  2. History of dimethyl sulfoxide (DMSO) reaction for either the child or mother.
  3. Parent(s)/child unwilling to participate.
  4. Child with severe chronic diseases, extensive extra-cardiac syndromic features, or history of cancer.
  5. Child not completing all pre-procedure work-up within 10 days of the Stage II Glenn surgery as listed in section 6 of this protocol AND lack of pre-procedure work-up documented as a safety concern by a site investigator.
  6. Child who's cells have been compromised after meeting cell release criteria (as defined in Inclusion Criterion #1).

  7. Child with the following complications of their congenital heart disease:

    1. Any condition requiring urgent, or unplanned procedure within 15 days prior to Stage II surgical repair
    2. Severe pulmonary hypertension (reported in the medical record as >70% systemic pressure)
    3. Other clinical concerns as documented by a site investigator that would predict (more likely to happen than not to happen) a risk of severe complications or very poor outcome during or after Stage II surgical repair.
Contacts and Locations
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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): NCT01883076


Locations
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United States, California
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
United States, Colorado
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
United States, Minnesota
Children's Hospital of Minnesota
Minneapolis, Minnesota, United States, 55404
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Oklahoma
Oklahoma University Children's Hospital
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Timothy J Nelson, MD, PhD
University of Oklahoma
Children's Hospital of Philadelphia
Children's Hospitals and Clinics of Minnesota
Children's Hospital Los Angeles
Children's Hospital Colorado
Mayo Clinic
Investigators
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Study Director: Timothy J Nelson, M.D., Ph.D. Mayo Clinic
Principal Investigator: Muhammad Y Qureshi, MBBS Mayo Clinic
Principal Investigator: Harold M Burkhart, M.D. Oklahoma University Children's Hospital
Principal Investigator: Joseph W Rossano, M.D. Children's Hospital of Philadelphia
Principal Investigator: David M Overman, M.D. Children's Hospital of Minnesota
Principal Investigator: Ram Kumar Subramanyan, M.D., Ph.D. Children's Hospital Los Angeles
Principal Investigator: James Jaggers, M.D. Children's Hospital Colorado
More Information
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Additional Information:

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Responsible Party: Timothy J Nelson, MD, PhD, Program Director, ReGen Theranostics, Inc.
ClinicalTrials.gov Identifier: NCT01883076    
Other Study ID Numbers: 12-008521
First Posted: June 21, 2013    Key Record Dates
Last Update Posted: April 29, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Timothy J Nelson, MD, PhD, ReGen Theranostics, Inc.:
Hypoplastic Left Heart Syndrome
HLHS
Congenital Heart Disease
Umbilical cord blood
UCB
 Cord blood
Stem cells
Regenerative therapy
Stage II Glenn
Glenn Surgery
Additional relevant MeSH terms:
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Hypoplastic Left Heart Syndrome
Syndrome
Disease
Pathologic Processes
Heart Defects, Congenital
 Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Congenital Abnormalities