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

This study has been terminated.
(Study has been terminated due to logistical barriers to cell processing and poor enrollment)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Columbia University
ClinicalTrials.gov Identifier:
NCT00383630
First received: September 29, 2006
Last updated: March 6, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Heart Failure, Congestive
Biological: Intramyocardial injection of bone marrow mononuclear cells
Biological: Intramyocardial injection of CD34+ selected bone marrow mononuclear cells
Device: LVAD alone
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Effect of Intramyocardial Injection of Immunoselected Bone Marrow Cells on Myocardial Function in LVAD Bridge to Transplant Patients

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Functional status [ Time Frame: Measured 90 days post-intervention ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 [ Time Frame: Measured at baseline, Days 45 and 90 post-intervention, every 60 days thereafter until transplant ] [ Designated as safety issue: Yes ]
  • Six Minute Walk [ Time Frame: Measured at Days 45 and 90 post-intervention, every 60 days thereafter until transplant ] [ Designated as safety issue: Yes ]
  • Duration of ability to tolerate wean [ Time Frame: Measured at Days 45 and 90 post-intervention, every 60 days thereafter until transplant ] [ Designated as safety issue: Yes ]
  • Neuronal function (specialized centers only) [ Time Frame: Measured at Days 45 and 90 post-intervention, every 60 days thereafter until transplant ] [ Designated as safety issue: Yes ]
  • Incidence of anti-HLA antibody sensitization while on LVAD support [ Time Frame: Measured at baseline, Days 7, 21, 45, and 90 days post-intervention, and every 60 days thereafter until transplant ] [ Designated as safety issue: Yes ]
  • Incidence of serious adverse events [ Time Frame: Event driven ] [ Designated as safety issue: Yes ]
  • Neovascularization and cardiomyocyte regeneration [ Time Frame: Measured at LVAD implant, at transplant, and at autopsy (if applicable) ] [ Designated as safety issue: Yes ]
  • Ability to tolerate wean from LVAD support for 30 minutes [ Time Frame: Measured at Days 45 and 90 post-intervention, every 60 days thereafter until transplant ] [ Designated as safety issue: Yes ]
  • Relationship of age to quantity of CD34+ bone marrow cells [ Time Frame: Measured post-implant ] [ Designated as safety issue: Yes ]

Enrollment: 1
Study Start Date: August 2007
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
Intramyocardial injection of bone marrow mononuclaear 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 Name: 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 Name: CD34+ selected BMCs + LVAD
Group 3
LVAD alone
Device: LVAD alone
LVAD implantation without any intramyocardial injection of bone marrow cells.
Other Name: LVAD alone

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 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, 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
  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: NCT00383630

Locations
United States, Illinois
Advocate Christ Medical Center
Oak Lawn, Illinois, United States, 60453
United States, Kentucky
Jewish Hospital
Louisville, Kentucky, United States, 40202
United States, New York
Columbia University
New York City, New York, United States, 10032
Montefiore Medical Center
New York City, New York, United States, 10467
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104-4227
United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53792-3236
St. Luke's Medical Center
Milwaukee, Wisconsin, United States, 53215
Sponsors and Collaborators
Columbia University
Investigators
Principal Investigator: Yoshifumi Naka, MD Columbia University
  More Information

No publications provided

Responsible Party: Columbia University
ClinicalTrials.gov Identifier: NCT00383630     History of Changes
Other Study ID Numbers: AAAC2128, P50HL077096, P50 HL077096-01
Study First Received: September 29, 2006
Last Updated: March 6, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Columbia University:
End Stage Heart Failure
LVAD
Bone Marrow Transplantation
Stem Cell Transplantation

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on August 26, 2014