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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2016 by Mayo Clinic
University of Oklahoma
Information provided by (Responsible Party):
Timothy J. Nelson, Mayo Clinic Identifier:
First received: June 11, 2013
Last updated: March 11, 2016
Last verified: March 2016

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 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 Intervention Phase
Hypoplastic Left Heart Syndrome
Biological: autologous cell-based delivery
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:

Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Number of patients completing consent, collection of umbilical cord blood, and intramyocardial delivery of autologous stem cells [ Time Frame: 1 week post Glenn procedure ] [ Designated as safety issue: Yes ]
    The percentage of patients consented for the study that have successfully undergone umbilical cord blood collection, completed GMP-processing to meet release criteria, and achieved uncomplicated intramyocardial cell delivery will determine the feasibility of this approach.

  • Number of patients with cardiac-related adverse events [ Time Frame: up to 6 months follow-up post Glenn procedure ] [ Designated as safety issue: Yes ]
    Upon intramyocardial cell delivery at the time of planned Glenn procedure, signs of cardiac toxicity will be measured according to worsening of ejection fraction by more than 10%, any new cardiac arrhythmias that could be attributed to stem cell therapy based on follow-up electrocardiograms and 24-hr Holter monitoring, and abnormal routine blood chemistry to monitor for evidence of organ failure.

Secondary Outcome Measures:
  • Change in right ventricular ejection fraction according to cardiac imaging with echocardiography [ Time Frame: 6 months follow-up post Glenn procedure ] [ Designated as safety issue: No ]
    The secondary analysis is focused on the potential benefit of intramyocardial delivery of the manufactured cell-based product in pediatric hearts at the time of planned surgical palliation for HLHS. The change from baseline to 1, 3, and 6-month follow-up in right ventricular ejection fraction is the primary variable along with secondary variables of change in right ventricle TAPSE and fractional area change.

Estimated Enrollment: 10
Study Start Date: May 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

Ages Eligible for Study:   up to 18 Months   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Individuals with autologous cord blood product enrolled, consented and collected under IRB #11-007176, that met all release criteria according to that protocol.
  • Individuals with HLHS undergoing planned Stage II palliative surgeries.
  • 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:

  • Individuals with UCB collected under consent and processed according to IRB #11-007176, not meeting specified release criteria or have not previously collected UCB.
  • History of DMSO reaction for either the infant or mother.
  • Individuals with families unwilling to participate.
  • Individuals with severe chronic diseases, extra-cardiac syndromes, or cancer.
  • Infants with the following conditions within 15 days prior to the date of the Stage II Glenn surgery:

    • Cardiogenic shock
    • Pulmonary hypertension requiring chronic medical therapy (e.g. supplemental oxygen, vasodilator)
    • Arrhythmia that required medication for control
    • Any documented infection requiring treatment with IV antibiotics, and/or current infection being treated with antibiotics
  • Infants with the following complications of their congenital heart disease:

    • Any cardiac condition requiring urgent, or unplanned procedure 15 days prior to Stage II Glenn surgery
    • Tricuspid repair and/or aortic arch repair at the time of Stage II Glenn surgery
    • Length of hospitalization of more than 60 days for Stage I Norwood procedure unless cardiac function is normal within 10 days prior to Glenn surgery
    • Chylothorax requiring dietary modifications
    • Seizure or neurological injury
    • Severe tricuspid regurgitation prior to Stage II Glenn surgery
    • History of extracorporeal membrane oxygenator (ECMO) support, unless cardiac function is normal within 10 days prior to Glenn surgery
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01883076

Contact: Karen S Miller (507) 266-5510
Contact: Karen M Cavanaugh (507) 538-8425

United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Karen S Miller    507-266-5510   
Contact: Karen M Cavanaugh    507- 538-8425   
Principal Investigator: Muhammad Y Qureshi, MBBS         
United States, Oklahoma
Oklahoma University Children's Hospital Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Stephanie Mitchell    405-271-2128   
Contact: Nicholas Farley    405-271-4411 ext 44403   
Principal Investigator: Harold M Burkhart, M.D.         
Sponsors and Collaborators
Timothy J. Nelson
University of Oklahoma
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
  More Information

Responsible Party: Timothy J. Nelson, Program Director, Mayo Clinic Identifier: NCT01883076     History of Changes
Other Study ID Numbers: 12-008521 
Study First Received: June 11, 2013
Last Updated: March 11, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
Hypoplastic Left Heart Syndrome
Congenital Heart Disease
Umbilical cord blood
Cord blood
Stem cells
Regenerative therapy
Stage II Glenn
Glenn Surgery

Additional relevant MeSH terms:
Hypoplastic Left Heart Syndrome
Pathologic Processes
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Congenital Abnormalities processed this record on October 21, 2016