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

Primary Purpose

Hypoplastic Left Heart Syndrome

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
autologous cell-based delivery
Sponsored by
Timothy J Nelson, MD, PhD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypoplastic Left Heart Syndrome focused on measuring Hypoplastic Left Heart Syndrome, HLHS, Congenital Heart Disease, Umbilical cord blood, UCB, Cord blood, Stem cells, Regenerative therapy, Stage II Glenn, Glenn Surgery

Eligibility Criteria

undefined - 18 Months (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Children's Hospital Los Angeles
  • Children's Hospital Colorado
  • Children's Hospital of Minnesota
  • Mayo Clinic
  • Oklahoma University Children's Hospital
  • Children's Hospital of Philadelphia

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

autologous cell-based delivery

Arm Description

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.

Outcomes

Primary Outcome Measures

Incidence of all-cause mortality
Incidence of new and worsening adverse cardiac events
The adverse cardiac events would include sustained/symptomatic ventricular arrhythmias, heart failure, myocardial infarction, cardiac infections, and unexpected cardiovascular surgery.
Percentage of subjects whose cells meet all cell release criteria
Percentage of subjects enrolled who undergo cell therapy treatment

Secondary Outcome Measures

Change in right ventricular ejection fraction at one month according to cardiac imaging with echocardiography
Change in right ventricular ejection fraction at 3 months according to cardiac imaging with echocardiography
Change in right ventricular ejection fraction at 6 months according to cardiac imaging with echocardiography
Change in right ventricle tricuspid annular plane systolic excursion (TAPSE) at one month according to cardiac imaging with echocardiography
Change in right ventricle TAPSE at 3 months according to cardiac imaging with echocardiography
Change in right ventricle TAPSE at 6 months according to cardiac imaging with echocardiography
Change in right ventricle fractional area change at one month according to cardiac imaging with echocardiography
Change in right ventricle fractional area change at 3 months according to cardiac imaging with echocardiography
Change in right ventricle fractional area change at 6 months according to cardiac imaging with echocardiography

Full Information

First Posted
June 11, 2013
Last Updated
April 28, 2022
Sponsor
Timothy J Nelson, MD, PhD
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
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1. Study Identification

Unique Protocol Identification Number
NCT01883076
Brief Title
Safety Study of Autologous Umbilical Cord Blood Cells for Treatment of Hypoplastic Left Heart Syndrome
Official Title
Phase I Safety Study of Autologous Umbilical Cord Blood Derived Mononuclear Cells During Surgical Stage II Palliation of Hypoplastic Left Heart Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
May 15, 2013 (Actual)
Primary Completion Date
April 28, 2021 (Actual)
Study Completion Date
April 28, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Timothy J Nelson, MD, PhD
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

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypoplastic Left Heart Syndrome
Keywords
Hypoplastic Left Heart Syndrome, HLHS, Congenital Heart Disease, Umbilical cord blood, UCB, Cord blood, Stem cells, Regenerative therapy, Stage II Glenn, Glenn Surgery

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
autologous cell-based delivery
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
autologous cell-based delivery
Other Intervention Name(s)
umbilical cord blood derived mononuclear cells
Intervention Description
autologous cells (derived from "self")
Primary Outcome Measure Information:
Title
Incidence of all-cause mortality
Time Frame
Within 2 years following cell therapy treatment
Title
Incidence of new and worsening adverse cardiac events
Description
The adverse cardiac events would include sustained/symptomatic ventricular arrhythmias, heart failure, myocardial infarction, cardiac infections, and unexpected cardiovascular surgery.
Time Frame
Within 2 years following cell therapy treatment
Title
Percentage of subjects whose cells meet all cell release criteria
Time Frame
Up to 2 years
Title
Percentage of subjects enrolled who undergo cell therapy treatment
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
Change in right ventricular ejection fraction at one month according to cardiac imaging with echocardiography
Time Frame
baseline, 1 month
Title
Change in right ventricular ejection fraction at 3 months according to cardiac imaging with echocardiography
Time Frame
baseline, 3 months
Title
Change in right ventricular ejection fraction at 6 months according to cardiac imaging with echocardiography
Time Frame
baseline, 6 months
Title
Change in right ventricle tricuspid annular plane systolic excursion (TAPSE) at one month according to cardiac imaging with echocardiography
Time Frame
baseline, 1 month
Title
Change in right ventricle TAPSE at 3 months according to cardiac imaging with echocardiography
Time Frame
baseline, 3 months
Title
Change in right ventricle TAPSE at 6 months according to cardiac imaging with echocardiography
Time Frame
baseline, 6 months
Title
Change in right ventricle fractional area change at one month according to cardiac imaging with echocardiography
Time Frame
baseline, 1 month
Title
Change in right ventricle fractional area change at 3 months according to cardiac imaging with echocardiography
Time Frame
baseline, 3 months
Title
Change in right ventricle fractional area change at 6 months according to cardiac imaging with echocardiography
Time Frame
baseline, 6 months

10. Eligibility

Sex
All
Maximum Age & Unit of Time
18 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria 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: No aerobic or anaerobic bacterial growth after 14 days Greater than 70% cell viability pre-freeze Total Nucleated Cells (TNC) concentration of 30-42 x 106 cells/mL (pre-freeze) Minimum of one (1) vial of cells Mononuclear cell percentage of greater than 50% Endotoxin result of less than 16 Endotoxin Units (EU)/mL. Mother's serology test results are negative for HIV, Hepatitis B, and Hepatitis C. Individuals with HLHS having undergone Stage I surgical palliation and undergoing planned Stage II palliative Glenn surgery. 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 Child who's UCB does not meet the specified cell release criteria in Inclusion Criterion #1. History of dimethyl sulfoxide (DMSO) reaction for either the child or mother. Parent(s)/child unwilling to participate. Child with severe chronic diseases, extensive extra-cardiac syndromic features, or history of cancer. 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. Child who's cells have been compromised after meeting cell release criteria (as defined in Inclusion Criterion #1). Child with the following complications of their congenital heart disease: Any condition requiring urgent, or unplanned procedure within 15 days prior to Stage II surgical repair Severe pulmonary hypertension (reported in the medical record as >70% systemic pressure) 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Timothy J Nelson, M.D., Ph.D.
Organizational Affiliation
Mayo Clinic
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Muhammad Y Qureshi, MBBS
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Harold M Burkhart, M.D.
Organizational Affiliation
Oklahoma University Children's Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Joseph W Rossano, M.D.
Organizational Affiliation
Children's Hospital of Philadelphia
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
David M Overman, M.D.
Organizational Affiliation
Children's Hospital of Minnesota
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ram Kumar Subramanyan, M.D., Ph.D.
Organizational Affiliation
Children's Hospital Los Angeles
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
James Jaggers, M.D.
Organizational Affiliation
Children's Hospital Colorado
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Children's Hospital of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Oklahoma University Children's Hospital
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
https://www.mayo.edu/research/clinical-trials
Description
Mayo Clinic Clinical Trials

Learn more about this trial

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

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