Bone Marrow Cell Transplantation to Improve Heart Function in Individuals With End-Stage Heart Failure

March 28, 2019 updated by: Yoshifumi Naka, Columbia University

The Effect of Intramyocardial Injection of Immunoselected Bone Marrow Cells on Myocardial Function in LVAD Bridge to Transplant Patients

Heart failure is a condition in which the heart is unable to pump enough blood to the body's other organs. A heart transplant may be necessary for some individuals with end-stage heart failure. Left ventricular assist devices (LVADs) can assist the heart in pumping blood, and are commonly used until a donor heart becomes available. Bone marrow cells injected into the heart may improve heart function and may lead to earlier LVAD removal. The purpose of this study is to evaluate the safety and effectiveness of injected bone marrow cells in improving heart function in individuals with LVADs who are awaiting heart transplants.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Congestive heart failure affects 5 million people in the United States, and over 60,000 are diagnosed with end-stage heart failure. Treatment options for these individuals are extremely limited. Because of a limited supply of donor organs, fewer than 3,000 people receive heart transplants each year. LVADs are battery-operated devices that can act as a temporary solution until a donor heart becomes available. Upon being surgically implanted into a weakened heart, the LVAD mechanically pumps blood from the heart to the rest of the body. There are, however, serious risks associated with LVADs, including infection, blood clots, and stroke. Early removal of the LVAD may be possible by injecting stem cells to regenerate new heart cells and improve heart function. The purpose of this study is to compare the safety and effectiveness of two types of bone marrow cells -- bone marrow mononuclear cells (BMCs) and immunoselected CD34+ hematopoietic stem cells -- in improving heart function in individuals with end-stage heart failure.

This study will enroll individuals undergoing surgery to receive an LVAD. Participants will be randomly assigned to one of following three groups:

Group 1 (n=30): participants will undergo intramyocardial injection of bone marrow mononuclear cells (BMCs) during LVAD implantation

Group 2 (n=30): participants will undergo intramyocardial injection of immunoselected CD34+ hematopoietic stem cells during LVAD implantation

Group 3 (n=15): participants will undergo LVAD implantation

Prior to LVAD implantation, participants in Groups 1 and 2 will have a sample of bone marrow removed. Following LVAD implantation, study visits will occur at Days 45 and 90, and then every 60 days thereafter until participants receive a heart transplant. At each visit, participants will undergo a LVAD wean procedure, during which the mechanical pump of the LVAD will be gradually turned off, and the LVAD will be operated with a hand pump. The length of time that a participant tolerates the wean procedure will be evaluated. Heart size and function, blood flow, and nerve function will also be assessed. Some participants will undergo a 6-minute walk test. At the time of heart transplant surgery, the LVAD will be removed, and heart cell regeneration and heart function will be evaluated.

Study Type

Interventional

Enrollment (Actual)

1

Phase

  • Phase 2

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

  • United States
    • Illinois
      • Oak Lawn, Illinois, United States, 60453
        • Advocate Christ Medical Center
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Jewish Hospital
    • New York
      • New York, New York, United States, 10032
        • Columbia University
      • New York, New York, United States, 10467
        • Montefiore Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104-4227
        • University of Pennsylvania
    • Wisconsin
      • Madison, Wisconsin, United States, 53792-3236
        • University of Wisconsin
      • Milwaukee, Wisconsin, United States, 53215
        • St. Luke's Medical Center

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

  • Signed informed consent, release of medical information, and Health Insurance Portability and Accountability Act (HIPAA) documents
  • Male, postmenopausal female, or female who may become pregnant but is using adequate contraceptive precautions (defined as use of oral contraceptive, intrauterine devices, surgical contraception, or a combination of a condom and a spermicide), with negative pregnancy test
  • Admitted to the clinical center at the time of study entry
  • Listed with United Network for Organ Sharing (UNOS) for cardiac transplantation
  • Clinical indication and accepted candidate for implantation of an FDA approved LVAD as a bridge to transplantation
  • Hemoglobin between 9.0 gm/dl and 16.1 gm/dl within 24 hours prior to study entry
  • Platelet count between 100,000/ul and 450,000/ul within 24 hours prior to study entry
  • White blood cell count between 2,500/ul and upper limit of normal within 24 hours prior to study entry

Exclusion Criteria

  • Cardiothoracic surgery within 30 days prior to study entry
  • Myocardial infarction within 6 months prior to study entry
  • Prior cardiac transplantation, left ventricular (LV) reduction surgery, or cardiomyoplasty
  • Acute reversible cause of heart failure (e.g., myocarditis, profound hypothyroidism)
  • Anticipated requirement for biventricular mechanical support
  • Stroke within 30 days prior to study entry
  • Received investigational intervention within 30 days of study entry
  • Pregnant or breastfeeding at time of study entry
  • HIV positive within 30 days prior to study entry
  • Active systemic infection within 48 hours prior to study entry

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group 1
Intramyocardial injection of bone marrow mononuclear cells + LVAD
Biological: Intramyocardial injection of bone marrow mononuclear cells
6mL of bone marrow mononuclear cells will be injected into the myocardium during LVAD implantation.
Other Names:
  • BMCs + LVAD
Experimental: Group 2
Intramyocardial injection of CD34+ selected bone marrow mononuclear cells + LVAD
Biological: Intramyocardial injection of CD34+ selected bone marrow mononuclear cells
6mL of CD34+ selected bone marrow mononuclear cells will be injected into the myocardium during LVAD implantation.
Other Names:
  • CD34+ selected BMCs + LVAD
Other: Group 3
LVAD alone
Device: LVAD alone
LVAD implantation without any intramyocardial injection of bone marrow cells.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of Time (Minutes) a Patient is Able to Tolerate Wean
Time Frame: Measured 90 days post-intervention
This defines the functional status. Due to poor enrollment, data was not analyzed.
Measured 90 days post-intervention

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prevalence of Normal Echocardiographic Assessments
Time Frame: Measured at baseline, Days 45 and 90 post-intervention, every 60 days thereafter until transplant

Echocardiographic assessments of myocardial size and function by transthoracic echocardiography with the LVAD at full support, and as tolerated at 1, 5, 10 and 15 minutes following initiation of hand pumping.

Due to poor enrollment, data was not analyzed.
Measured at baseline, Days 45 and 90 post-intervention, every 60 days thereafter until transplant
Number of Patients Who Completed a Six Minute Walk
Time Frame: Measured at Days 45 and 90 post-intervention, every 60 days thereafter until transplant

6 Minute walk as tolerated at 15 minutes following initiation of hand pumping.

Due to poor enrollment, results was not analyzed.
Measured at Days 45 and 90 post-intervention, every 60 days thereafter until transplant

Collaborators and Investigators

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

Sponsor

Columbia University

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

  • Principal Investigator: Yoshifumi Naka, MD, Columbia University

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

September 1, 2007

Primary Completion (Actual)

December 1, 2008

Study Completion (Actual)

December 1, 2008

Study Registration Dates

First Submitted

September 29, 2006

First Submitted That Met QC Criteria

September 29, 2006

First Posted (Estimate)

October 3, 2006

Study Record Updates

Last Update Posted (Actual)

April 17, 2019

Last Update Submitted That Met QC Criteria

March 28, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AAAC2128
  • P50HL077096 (U.S. NIH Grant/Contract)
  • P50HL077096-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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