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LVAD Patient Abstract

STUDY TITLE: LVAD THERAPY: EXPLORING THE EFFECT OF INTRAMYOCARDIAL INJECTION OF MESENCHYMAL PRECURSOR CELLS ON MYOCARDIAL FUNCTION

CURRENT STATUS: Enrolling

What is the purpose of this research?
The main purpose of this research is to determine whether injecting mesenchymal precursor cells (MPC) into the heart during surgery to implant a left ventricular assist device (LVAD) is safe and effective in improving heart function. MPCs are normally present in human bone marrow, and have been shown to increase the development of blood vessels and new heart muscle cells in the heart. This study will test to see if these effects are enough to improve overall heart function. The stem cells being tested in this study, RevascorTM, (manufactured by Angioblast Systems, Inc.), are obtained from one healthy person and are grown in the laboratory. This study will compare the heart function of patients who receive injection of one dose of the ResvascorTM to patients who receive injection of a control solution (cell preservative without the cells) at the time of LVAD implantation surgery.

Who can be in this study?
People who are scheduled for surgery to implant an LVAD as either bridge-to-transplant (BTT) or as destination therapy (DT) may participate in this study. There will be a total of 30 patients enrolled in this study in up to 25 medical centers across the United States.

Who cannot be in this study?
Some reasons a person may not be able to participate in this research study include: prior transplant surgery, a current pregnancy, a history of cancer prior to surgery, or having a heart attack within one month of study enrollment.

What procedures will be followed?
Participants in this study will have a number of tests before planned LVAD surgery to (1) determine whether they are eligible to participate in this study, and (2) to determine their baseline results for several tests that will be repeated at times after receipt of the study injection and LVAD implantation. Some of these tests will look at baseline antibody production and characteristics and function of certain blood cells. Prior to the LVAD surgery, participants will undergo additional testing including an echocardiogram, which is a sound wave picture of the heart to look at function, and neurocognitive tests (tests of thinking and understanding). The neurocognitive tests will be audiotaped.

For women who can become pregnant, a urine or blood pregnancy test will be required. If a blood pregnancy test is being done, an additional teaspoon of blood will be collected and sent to the hospital's laboratory.

Treatment Assignment
Before LVAD surgery, participants will be assigned by chance (like a coin toss) to one of two groups. Group 1 (20 patients) will have stem cells called RevascorTM injected into the heart muscle and Group 2 (10 patients) will receive control solution (cell preservative without the cells) injections instead of cells.

Study Injection during LVAD Surgery
The total amount of material injected into the heart during the LVAD surgery will be about 1 teaspoon. Neither participants nor study doctors or surgeons will know whether each participant received the stem cells or the control solution injections. When the LVAD is implanted, a piece of the heart muscle, which is routinely removed to insert the LVAD, will be collected and sent for analysis for certain cell functions and characteristics.

Monitoring after LVAD Surgery
Participants will continue to be followed until 12 months following LVAD implantation or until they receive a heart transplant (BTT patients), whichever comes first. Participants will be seen by a study doctor who will take a history and examine them on day 1, 7, 21, 45, 60 and 90 days after LVAD surgery. This will then be repeated every 60 days until 12 months following LVAD implantation or heart transplant (BTT patients), whichever comes first. During the 90 day visit, neurocognitive testing (tests of thinking and understanding) will also be conducted during the clinic visit. The neurocognitive tests will be audiotaped.

In addition to the routine (standard of care) blood samples collected during clinic visits, study blood samples will be collected to measure changes, if any, in antibody production and function and characteristics of certain cells. Study samples to measure changes in antibody production will be collected on days 30 and 90, month 6 and month 12 after surgery. Study samples to measure function and characteristics of certain cells will be collected on days 1, 7, 30, 60 and 90, and months 6 and 12 following surgery or until heart transplant, whichever comes first.

Heart function will be tested to determine if it has improved at 30, 60 and 90 days following the LVAD, and then every 2 months thereafter until heart transplant (BTT patients) or until 12 months following LVAD implantation, whichever comes first. Two tests will be performed. The tests will be performed while the LVAD is weaned, which is when the LVAD flow is lowered. Some doctors perform LVAD weaning following LVAD placement to see whether or not the heart muscle function improved. For the purposes of this study, the LVAD will be weaned at the specified time points if the study doctor feels you are clinically stable. During the LVAD wean, participants may receive heparin (a medicine that makes your blood thinner) in the vein before turning the LVAD flow down to prevent formation of blood clots if your doctor deems it appropriate. While the flow is turned down, heart rhythm and blood pressure will be closely monitored. If a participant develop dizziness, lightheadedness, shortness of breath, chest pain, or experience any symptom that doctors believe may jeopardize the participant's health, the LVAD will be returned to full flow. The first test performed during the LVAD wean is an echocardiogram to obtain a picture of how the heart is pumping. The echocardiogram will be repeated several times while the LVAD is weaned. The second test that is called the 6-minute walk test. During this test participants will be asked to walk in the hospital hallway for 6 minutes, and we will record how far you can go.

Right Heart Catheterization
The right heart catheterization procedure is widely used in caring for patients with heart disease, however it may not be part of routine care. The procedure will be completed up to three times, once before the LVAD device implant, 60 days after implant and again at 90 days after implant. The first procedure will be considered routine care, but the 60- and 90-day procedures are considered research procedures and will be paid for by the study.

The catheterization is performed in the catheterization lab while lying flat. The physician places a very small thin flexible tube (called a catheter) into a large vein in the groin or neck and threads it through that vein to the heart. Participants will be given drugs to numb the area where the catheter is inserted. A catheter is then moved to different positions in the heart to get pressure readings (like a blood pressure). In the middle of the procedure the doctor will start a medication called dobutamine (this will only be done at 60 and 90 days only). Dobutamine is a Food and Drug Administration (FDA) approved medicine used for treatment of depressed cardiac contractility, which means the heart is not pumping well. The medicine acts by increasing the pumping action of the heart. It is given through an IV (catheter placed in a vein) and starts working within 1 or 2 minutes. The peak effect of the medicine may not be reached till about 10 minutes. This medicine is being given to you during your right heart catheterization as a way to challenge your heart muscle and see how pumping action and pressure readings of your heart respond. After about 30 minutes, the doctor will repeat the pressure readings. Once the right heart catheterization has been completed and all the pressures recorded, the medicine will be stopped.

What are the possible risks of being in this study?
Your surgeon will discuss all risks with you prior to the surgery. The risks of LVAD surgery are present whether you participate in the research study or not.

As with any investigational agent, all side effects may not be known, and unexpected complications may occur. If you take part in this study, the known potential risks to you will be discussed with you by the study doctor.

Possible risks of treatment with stem cells may include abnormal growth of cells at the site of injection (formation of tumor), sensitivity reaction ("allergy" to the study injection), infection, and inflammation. Also, the injection into the heart itself can produce an abnormal heart rhythm.

Some of the potential symptoms of the LVAD flow being lowered may include dizziness, lightheadedness, and shortness of breath or chest pain. If these should occur, the weaning will be stopped. Another risk of lowering LVAD flow is blood clot formation. Because of this, patients with certain risk factors for clot formation will be given blood thinner medicines before and during the test to prevent clot formation. There is a small chance that the blood thinner can cause bleeding, although you will be monitored closely for this possible side-effect.

The known side effects of the right heart catheterization are: irregular heartbeat; bleeding, pain or infection at the site of catheter insertion; a full or partial collapse of the lung which can occur when air leaks into the space between your lung and chest wall (known as a pneumothorax); collection of blood in the space between the chest wall and the lung (known as a hemothorax); damage to blood vessels; and blood clots.

The known side effects of dobutamine are: increased blood pressure; increase in heart rate; chest pressure/pain; irregular heartbeats (palpitations); shortness of breath; nausea/vomiting; and headache.

With genetic studies, there is a potential risk of loss of confidentiality; to minimize this risk, your samples will not be used in any paternity determination tests. The results of these tests will not have an effect on your care. To avoid potential discrimination from your employer or your medical insurance, neither your doctor nor you will receive results of these research genetic tests, nor will the results be put in your health record. You may have some pain or discomfort, bleeding, or bruising at areas of blood drawing.

What are the possible benefits of being in this study?
Participants may not personally benefit from receiving the study injection, but it is possible that the therapy with cells may stimulate improvement of heart muscle function. Although there is preliminary information that suggests that the cells may benefit weakened hearts not caused by coronary artery disease, this has not yet been proven, so this trial may help explore this potential benefit.

How long will I be in the study?
Participants will be asked to continue in this study until 12 months following LVAD implantation or until heart transplant (BTT patients), whichever comes first. Participation in this study will not prevent or delay heart transplant surgery (BTT patients).

What are the costs to be in this study?
Taking part in this study will not involve additional costs to participants. All study specific tests will be paid for by the study sponsor. Participants and/or their insurance companies will have to pay for any costs that are part of regular medical care. Anything not paid by health insurance for medical care will be billed directly to participants for payment.

Participants will not receive any compensation for participation in this research study.

Who is funding this research? This research is being supported by a research grant from the following government programs:
•  National Heart, Lung, and Blood Institute (NHLBI)
•  National Institute of Neurological Disorders and Stroke (NINDS)
•  Canadian Institutes of Health Research (CIHR)
•  Angioblast Systems, Inc

For Further Information about the Study and Enrollment
If you are interested in participating in this research you may contact one of the CTSN or CCTRN participating sites. For contact information, please click here.

For any additional questions, you may send an email to the Mount Sinai Data Coordinating Center:
•  Ellen Moquete, RN, BSN, ellen.moquete@mountsinai.org, 212-659-9651 or
•  Janine Lynch, MPH, Janine.lynch@mountsinai.org, 212-659-9631 or
•  Deborah Ascheim, MD, deborah.ascheim@mountsinai.org, 212-659-9612

For more information about this study, please visit
http://clinicaltrials.gov/ct2/show/NCT01442129

Initial annual IRB approval period: 10/25/11 - 10/10/12