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

April 28, 2022 updated by: Timothy J Nelson, MD, PhD

Phase I Safety Study of Autologous Umbilical Cord Blood Derived Mononuclear Cells During Surgical Stage II Palliation of Hypoplastic Left Heart Syndrome

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.

Study Overview

Status

Completed

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 Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • California
      • Los Angeles, California, United States, 90027
        • Children's Hospital Los Angeles
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Children's Hospital Colorado
    • Minnesota
      • Minneapolis, Minnesota, United States, 55404
        • Children's Hospital of Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Oklahoma University Children's Hospital
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 2 months (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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.
autologous cells (derived from "self")
Other Names:
  • umbilical cord blood derived mononuclear cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of all-cause mortality
Time Frame: Within 2 years following cell therapy treatment
Within 2 years following cell therapy treatment
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.
Within 2 years following cell therapy treatment
Percentage of subjects whose cells meet all cell release criteria
Time Frame: Up to 2 years
Up to 2 years
Percentage of subjects enrolled who undergo cell therapy treatment
Time Frame: Up to 2 years
Up to 2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Change in right ventricular ejection fraction at one month according to cardiac imaging with echocardiography
Time Frame: baseline, 1 month
baseline, 1 month
Change in right ventricular ejection fraction at 3 months according to cardiac imaging with echocardiography
Time Frame: baseline, 3 months
baseline, 3 months
Change in right ventricular ejection fraction at 6 months according to cardiac imaging with echocardiography
Time Frame: baseline, 6 months
baseline, 6 months
Change in right ventricle tricuspid annular plane systolic excursion (TAPSE) at one month according to cardiac imaging with echocardiography
Time Frame: baseline, 1 month
baseline, 1 month
Change in right ventricle TAPSE at 3 months according to cardiac imaging with echocardiography
Time Frame: baseline, 3 months
baseline, 3 months
Change in right ventricle TAPSE at 6 months according to cardiac imaging with echocardiography
Time Frame: baseline, 6 months
baseline, 6 months
Change in right ventricle fractional area change at one month according to cardiac imaging with echocardiography
Time Frame: baseline, 1 month
baseline, 1 month
Change in right ventricle fractional area change at 3 months according to cardiac imaging with echocardiography
Time Frame: baseline, 3 months
baseline, 3 months
Change in right ventricle fractional area change at 6 months according to cardiac imaging with echocardiography
Time Frame: baseline, 6 months
baseline, 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Muhammad Y Qureshi, MBBS, Mayo Clinic
  • Study Director: Timothy J Nelson, M.D., Ph.D., 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 15, 2013

Primary Completion (Actual)

April 28, 2021

Study Completion (Actual)

April 28, 2021

Study Registration Dates

First Submitted

June 11, 2013

First Submitted That Met QC Criteria

June 20, 2013

First Posted (Estimate)

June 21, 2013

Study Record Updates

Last Update Posted (Actual)

April 29, 2022

Last Update Submitted That Met QC Criteria

April 28, 2022

Last Verified

April 1, 2022

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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