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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 October 2016 by Mayo Clinic
Sponsor:
Collaborator:
University of Oklahoma
Information provided by (Responsible Party):
Timothy J. Nelson, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01883076
First received: June 11, 2013
Last updated: October 25, 2016
Last verified: October 2016
  Purpose

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 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:
  • Incidence of all-cause mortality [ Time Frame: Within 2 years following cell therapy treatment ] [ Designated as safety issue: Yes ]
  • Incidence of new and worsening adverse cardiac events [ Time Frame: Within 2 years following cell therapy treatment ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Percentage of subjects enrolled who undergo cell therapy treatment [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in right ventricular ejection fraction at one month according to cardiac imaging with echocardiography [ Time Frame: baseline, 1 month ] [ Designated as safety issue: No ]
  • Change in right ventricular ejection fraction at 3 months according to cardiac imaging with echocardiography [ Time Frame: baseline, 3 months ] [ Designated as safety issue: No ]
  • Change in right ventricular ejection fraction at 6 months according to cardiac imaging with echocardiography [ Time Frame: baseline, 6 months ] [ Designated as safety issue: No ]
  • Change in right ventricle tricuspid annular plane systolic excursion (TAPSE) at one month according to cardiac imaging with echocardiography [ Time Frame: baseline, 1 month ] [ Designated as safety issue: No ]
  • Change in right ventricle TAPSE at 3 months according to cardiac imaging with echocardiography [ Time Frame: baseline, 3 months ] [ Designated as safety issue: No ]
  • Change in right ventricle TAPSE at 6 months according to cardiac imaging with echocardiography [ Time Frame: baseline, 6 months ] [ Designated as safety issue: No ]
  • Change in right ventricle fractional area change at one month according to cardiac imaging with echocardiography [ Time Frame: baseline, 1 month ] [ Designated as safety issue: No ]
  • Change in right ventricle fractional area change at 3 months according to cardiac imaging with echocardiography [ Time Frame: baseline, 3 months ] [ Designated as safety issue: No ]
  • Change in right ventricle fractional area change at 6 months according to cardiac imaging with echocardiography [ Time Frame: baseline, 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 10
Study Start Date: May 2013
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (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.
  Eligibility

Ages Eligible for Study:   up to 18 Months   (Child)
Genders Eligible for Study:   Both
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 with, or reasonably expected to have, complications during the Stage II Glenn surgery or during post-operative recovery.
  7. Child who's cells have been compromised after meeting cell release criteria (as defined in Inclusion Criterion #1).
  8. Child with the following conditions within 15 days prior to the date of the Stage II Glenn surgery:

    1. Cardiogenic shock
    2. Changes in medical therapy (e.g. supplemental oxygen, vasodilator) for pulmonary hypertension
    3. Changes in arrhythmia medications
    4. A current infection being treated with oral antibiotics or treatment with IV antibiotics within the past 15 days.
  9. 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 Glenn surgery
    2. Tricuspid repair and/or aortic arch repair at the time of Stage II Glenn surgery
    3. Length of hospitalization of more than 60 days for Stage I surgical palliation, unless cardiac function is normal within 10 days prior to Glenn Surgery
    4. Dietary modifications due to chronic and severe chylothorax
    5. Current or uncontrolled seizure(s) or neurological injury that has resulted in a persistent deficit
    6. Severe tricuspid regurgitation prior to Stage II Glenn surgery
    7. History of mechanical circulatory support, unless cardiac function is normal within 10 days prior to Glenn surgery
    8. Other clinical concerns as documented by a site investigator that could reasonably increase the risk of complications during or after Stage II 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 ClinicalTrials.gov identifier: NCT01883076

Contacts
Contact: Karen S Miller (507) 266-5510 miller.karen1@mayo.edu
Contact: Karen M Cavanaugh (507) 538-8425 cavanaugh.karen@mayo.edu

Locations
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Karen S Miller    507-266-5510    miller.karen1@mayo.edu   
Contact: Karen M Cavanaugh    507- 538-8425    cavanaugh.karen@mayo.edu   
Principal Investigator: Muhammad Y Qureshi, MBBS         
United States, Oklahoma
Oklahoma University Children's Hospital Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Karla Gourley    405-271-8001    karla-gourley@ouhsc.edu   
Contact: Nicholas Farley    405-271-4411 ext 44403    nicholas-farley@ouhsc.edu   
Principal Investigator: Harold M Burkhart, M.D.         
Sponsors and Collaborators
Timothy J. Nelson
University of Oklahoma
Investigators
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
ClinicalTrials.gov Identifier: NCT01883076     History of Changes
Other Study ID Numbers: 12-008521 
Study First Received: June 11, 2013
Last Updated: October 25, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
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:
Syndrome
Hypoplastic Left Heart Syndrome
Disease
Pathologic Processes
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Congenital Abnormalities

ClinicalTrials.gov processed this record on December 02, 2016