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

NCT ID: NCT01883076

Last Updated: 2022-04-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-05-15

Study Completion Date

2021-04-28

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Hypoplastic Left Heart Syndrome

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

autologous cell-based delivery

Intervention Type BIOLOGICAL

autologous cells (derived from "self")

Interventions

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autologous cell-based delivery

autologous cells (derived from "self")

Intervention Type BIOLOGICAL

Other Intervention Names

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umbilical cord blood derived mononuclear cells

Eligibility Criteria

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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.
Maximum Eligible Age

18 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Oklahoma

OTHER

Sponsor Role collaborator

Children's Hospital of Philadelphia

OTHER

Sponsor Role collaborator

Children's Hospitals and Clinics of Minnesota

OTHER

Sponsor Role collaborator

Children's Hospital Los Angeles

OTHER

Sponsor Role collaborator

Children's Hospital Colorado

OTHER

Sponsor Role collaborator

Mayo Clinic

OTHER

Sponsor Role collaborator

Timothy J Nelson, MD, PhD

OTHER

Sponsor Role lead

Responsible Party

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Timothy J Nelson, MD, PhD

Program Director

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Timothy J Nelson, M.D., Ph.D.

Role: STUDY_DIRECTOR

Mayo Clinic

Muhammad Y Qureshi, MBBS

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Harold M Burkhart, M.D.

Role: PRINCIPAL_INVESTIGATOR

Oklahoma University Children's Hospital

Joseph W Rossano, M.D.

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

David M Overman, M.D.

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Minnesota

Ram Kumar Subramanyan, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital Los Angeles

James Jaggers, M.D.

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital Colorado

Locations

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Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status

Children's Hospital of Minnesota

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Oklahoma University Children's Hospital

Oklahoma City, Oklahoma, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

Related Links

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Other Identifiers

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12-008521

Identifier Type: -

Identifier Source: org_study_id

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