Heart Failure, Congestive
Conditions
Keywords
End Stage Heart Failure, LVAD, Bone Marrow Transplantation, Stem Cell Transplantation
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.
Interventions
BIOLOGICALIntramyocardial injection of bone marrow mononuclear cells
6mL of bone marrow mononuclear cells will be injected into the myocardium during LVAD implantation.
BIOLOGICALIntramyocardial 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.
DEVICELVAD alone
LVAD implantation without any intramyocardial injection of bone marrow cells.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Columbia University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Time (Minutes) a Patient is Able to Tolerate Wean | Measured 90 days post-intervention | This defines the functional status. Due to poor enrollment, data was not analyzed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Prevalence of Normal Echocardiographic Assessments | 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. |
| Number of Patients Who Completed a Six Minute Walk | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Study Subjects Total number of subjects in the study; breakdown of the number per arm is not available. | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | Study Subjects |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 1 / 1 |
Outcome results
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.
Time frame: Measured 90 days post-intervention
Population: The study was terminated early due to logistical barriers to cell processing and poor enrollment and therefore sufficient data was not obtained for data analysis. Data analysis could not be performed.
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.
Time frame: Measured at Days 45 and 90 post-intervention, every 60 days thereafter until transplant
Population: The study was terminated early due to logistical barriers to cell processing and poor enrollment and therefore sufficient data was not obtained for data analysis. Data analysis could not be performed.
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.
Time frame: Measured at baseline, Days 45 and 90 post-intervention, every 60 days thereafter until transplant
Population: The study was terminated early due to logistical barriers to cell processing and poor enrollment and therefore sufficient data was not obtained for data analysis. Data analysis could not be performed.