STUDY TITLE: SAFETY & EFFICACY OF INTRAMYOCARDIAL INJECTION OF MESENCHYMAL PRECURSOR CELLS ON MYOCARDIAL FUNCTION IN LVAD RECIPIENTS
Current Status: Enrollment Complete
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. In addition, this research is being done to test whether injecting the MPCs into the heart is 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 Mesoblast Ltd.), are obtained from healthy human donors 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. Revascor, the MPC used in this trial, is an investigational product, meaning that it has not been approved by the FDA.
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 120 patients enrolled in this study in a number of medical centers (up to 25) across the United States and Canada.
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 most cancers 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, 60 and 90 days after LVAD surgery and at 6, 9 and 12 months after LVAD surgery. During the 90 day and 12 months visits, neurocognitive testing (tests of thinking and understanding) will also be conducted during the clinic visit. During the 6 and 12 months visits, participants will be asked to complete quality of life questionnaires.
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 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 characteristics of certain cells will be collected on days 1, 7, 30, 60 and 90, and months 6, 9 and 12 following surgery or until heart transplant, whichever comes first. The total amount of study blood collected during the first 3 months after surgery is 12 tablespoons. From then on, study blood samples will only be collected at months 6, 9 and 12 and the total amount collected at each visit is 3 tablespoons.
Heart function will be tested to determine if it has improved at 60 and 90 days following the LVAD, and then at 6, 9 and 12 months following LVAD implantation. 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 patient is clinically stable. During the LVAD wean, patients may receive heparin before turning the LVAD flow down to prevent formation of blood clots if appropriate. While the flow is turned down, heart rhythm and blood pressure will be closely monitored. If a patient develops dizziness, lightheadedness, shortness of breath, chest pain, or experiences any symptom may jeopardize the patient's health, the LVAD will be returned to full flow. The first test performed during the LVAD wean is an echocardiogram. The echocardiogram will be repeated several times while the LVAD is weaned. The second test is a 6-minute walk test.
What are the possible risks of being in this study?
The risks of LVAD surgery will be discussed with all patients prior to the surgery. These risks are present regardless of study participation.
As with any investigational agent, all side effects may not be known, and unexpected complications may occur.
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 patients will be monitored closely for this possible side-effect. With genetic studies, there is a potential risk of loss of confidentiality; to minimize this risk, samples will not be used in any paternity determination tests. The results of these tests will not have an effect on care. To avoid potential discrimination from employers or medical insurance, neither study staff nor patients will receive results of these research genetic tests, nor will the results be put in the health record.
Patients may have some pain or discomfort, bleeding, or bruising at areas of blood drawing. Some people feel uncomfortable when answering questions about the quality of their life. Though it is always better to have fully completed questionnaires, patients do not need to answer any questions that make them feel uncomfortable.
Pregnancy
It is unknown whether Revascor has side effects that pose a risk to a fetus or a nursing infant. For women who can become pregnant, a urine or blood pregnancy test will be required before you can enter this study. Women who are pregnant will not be allowed to be a part of the study.
No one method of contraception is 100% effective. In order to avoid pregnancy, the use of two forms of contraception, including at least one highly effective method, is recommended. Highly effective methods of contraception include: hormonal contraceptives such as oral contraceptives (the pill), patch, vaginal ring, injectables, and implants; intrauterine device (IUD); vasectomy and tubal ligation.
In the event that a patient is confirmed to be pregnant during the study, we will collect health information from the patient regarding the course of the pregnancy and the first year of the infant's life.
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.
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)
• Mesoblast, 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 participating sites. For contact information, please click here.
For any additional questions, you may contact the Data Coordinating Center at the Icahn School of Medicine at Mount Sinai in New York City:
• Ellen Moquete, RN, BSN, ellen.moquete@mountsinai.org, 212-659-9651
GCO # 08-1078(8); Current IRB approval period 12/2/19-12/1/20
Principal Investigator: Annetine C. Gelijns, PhD
For more information about this study, please visit
https://www.clinicaltrials.gov/ct2/show/NCT02362646?term=NCT02362646&rank=1
