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

Heart Failure, Congestive Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00383630
• Other study ID #: AAAC2128
• Secondary ID: P50HL077096P50HL
• Status: Terminated
• Phase: Phase 2
• Start date: September 2007
• Est. completion date: December 2008

Study information

• Verified date: March 2019
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: December 2008
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure, Congestive

Intervention

Biological:
• Intramyocardial injection of bone marrow mononuclear cells
6mL of bone marrow mononuclear cells will be injected into the myocardium during LVAD implantation.
• 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.

Device:
• LVAD alone
LVAD implantation without any intramyocardial injection of bone marrow cells.

Locations

Country	Name	City	State
United States	Jewish Hospital	Louisville	Kentucky
United States	University of Wisconsin	Madison	Wisconsin
United States	St. Luke's Medical Center	Milwaukee	Wisconsin
United States	Columbia University	New York	New York
United States	Montefiore Medical Center	New York	New York
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Columbia University	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Duration of Time (Minutes) a Patient is Able to Tolerate Wean	This defines the functional status. Due to poor enrollment, data was not analyzed.	Measured 90 days post-intervention
Secondary	Prevalence of Normal Echocardiographic Assessments	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
Secondary	Number of Patients Who Completed a Six Minute Walk	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