Clinical trial NCT00383630: Bone Marrow Cell Transplantation to Improve Heart Function in Individuals With End-Stage Heart Failure
Official title: The Effect of Intramyocardial Injection of Immunoselected Bone Marrow Cells on Myocardial Function in LVAD Bridge to Transplant Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Heart Failure, Congestive
Keywords: End Stage Heart Failure
LVAD
Bone Marrow Transplantation
Stem Cell Transplantation
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2006-10-03
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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 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

Primary outcomes:
measure: Duration of Time (Minutes) a Patient is Able to Tolerate Wean
timeFrame: Measured 90 days post-intervention
Secondary outcomes:
measure: Prevalence of Normal Echocardiographic Assessments
timeFrame: Measured at baseline, Days 45 and 90 post-intervention, every 60 days thereafter until transplant
measure: Number of Patients Who Completed a Six Minute Walk
timeFrame: Measured at Days 45 and 90 post-intervention, every 60 days thereafter until transplant
Other outcomes:
Locations:
city: Oak Lawn
country: United States
facility: Advocate Christ Medical Center
state: Illinois
city: Louisville
country: United States
facility: Jewish Hospital
state: Kentucky
city: New York
country: United States
facility: Columbia University
state: New York
city: New York
country: United States
facility: Montefiore Medical Center
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: St. Luke's Medical Center
state: Wisconsin
Study officials:
affiliation: Columbia University
name: Yoshifumi Naka, MD
role: PRINCIPAL_INVESTIGATOR
References: