Effect of Intramyocardial Injection of Mesenchymal Precursor Cells on Heart Function in People Receiving an LVAD

Congestive heart failure is a major health problem and recent estimates indicate that
end-stage heart failure with a 2-year mortality rate of 70-80% affects over 60,000 people in
the United States each year. For these patients, treatment options are extremely limited.
Less than 3,000 heart transplants are available each year because of the severely limited
supply of donor hearts. Implantable LVADs, routinely used to support heart transplantation
patients who decompensate awaiting a donor heart, were approved by the Food and Drug
Administration (FDA) in 2002 for long-term support when heart transplantation is not an
option. Few patients, however, achieve sufficient recovery to warrant LVAD explantation and
those who do must still contend with ventricular dysfunction. MPCs are normally present in
human bone marrow and have been shown to increase the development of blood vessels and new
heart muscle cells. The purpose of this study is to determine the safety of injecting MPCs
into the heart during LVAD implantation surgery. In addition, this study will examine whether
injecting MPCs into the heart is effective at improving heart function.

This study will enroll people who are on the waiting list to receive a donor heart and who
are undergoing LVAD implantation surgery. Before the surgery, participants will be randomly
assigned to one of two groups. One group of participants will have MPCs injected into their
heart during LVAD surgery and the other group of participants will have a control solution
(placebo) injected into their heart during the surgery. A portion of heart muscle removed
during the surgery will be analyzed. Participants will be monitored by study researchers and
blood samples will be collected 12 hours after the LVAD surgery and at 1, 7, 21, 60, and 90
days after the surgery. After that, a medical history review, physical examination, and blood
collection will occur every 60 days until a heart transplant occurs or until 12 months after
the LVAD implantation, whichever comes first. Heart function testing, which will include an
echocardiogram, neuronal function testing, and a 6-minute walk test, will occur 60 and 90
days after the LVAD implantation, and every 2 months thereafter until a heart transplant
occurs or until 12 months after the LVAD implantation, whichever comes first.

Inclusion Criteria:

- Signed informed consent, release of medical information, and Health Insurance
Portability and Accountability Act (HIPAA) documents

- Age 18 years or older

- If the participant or partner is of childbearing potential, he or she must be willing
to use adequate contraception (hormonal or barrier method or abstinence) from the time
of screening and for a period of at least 16 weeks after LVAD implantation

- Female participants of childbearing potential must have a negative serum pregnancy
test at screening

- Admitted to the clinical center at the time of study entry

- Listed with the United Network for Organ Sharing (UNOS) for heart transplantation

- Clinical indication and accepted candidate for implantation of an FDA- approved LVAD
as a bridge to transplantation

Exclusion Criteria:

- Cardiothoracic surgery within 30 days of study entry

- Heart attack within 30 days of study entry

- Prior heart 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 of study entry

- Received investigational intervention within 30 days of study entry

- Platelet count less than 100,000/uL within 24 hours of study entry

- Active systemic infection within 48 hours of study entry

- Presence of greater than 10% anti-human leukocyte antigen (HLA) antibody titers with
known specificity to the MPC donor HLA antigens

- Known hypersensitivity to dimethyl sulfoxide (DMSO), murine, and/or bovine products

- History of cancer prior to screening (excluding basal cell carcinoma)

- Acute or chronic infectious disease, including but not limited to human
immunodeficiency virus (HIV)

- Treatment and/or an incompleted follow-up treatment of any investigational therapy
within 6 months of study entry

- Active participation in other research therapy for cardiovascular repair/regeneration

- Prior recipient of stem precursor cell therapy for cardiac repair

- Pregnant or breastfeeding at the time of study entry