A Phase I Randomized, Dose Escalation Study of the Safety and Efficacy of Intracoronary Delivery of Cardiosphere-Derived Stem Cells in Patients With Ischemic Left Ventricular Dysfunction and a Recent Myocardial Infarction
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 4
- 主要终点
- The primary objective is to demonstrate the safety of autologous cardiosphere-derived stem cells administered by intra-coronary infusion in patients with ischemic left ventricular dysfunction and a recent myocardial infarction.
研究概览
简要总结
The purpose of this study is to determine whether giving cardiosphere-derived stem cells (CDCs) to patients with decreased heart function and/or a large amount of damaged muscle after a heart attack is safe. CDCs are cells grown from small biopsy samples taken from the heart. Giving a patient their own CDCs is an investigational procedure that has been approved by the Food and Drug Administration for this study. In addition to determining whether this treatment is safe, the study will also examine whether it can decrease the amount of heart muscle damage and/or improve heart function after a heart attack. The amount of heart muscle damage and the function of the heart directly affects prognosis (the predicted course of the disease), and the development of heart failure and other complications some patients experience after a heart attack.
By way of background, scientists and physicians believed, until just a few years ago, that heart muscle damaged after a heart attack could not be replaced. Recently, however, scientists discovered that new heart muscle can form, or be regenerated, and that this process can be enhanced (or increased) by the administration of large numbers of certain cells isolated from the heart or bone marrow. These cells can be stem cells, or cells derived from stem cells, and they may achieve their benefit by forming new heart muscle cells, becoming heart muscle cells themselves, or releasing substances which increase the ability of already existing stem cells to form new heart muscle. All of the studies conducted so far have been experimental and no cell type is approved for routine clinical care of patients with heart disease. However, studies involving bone marrow stem cells do indicate some small improvement in heart function and one large study demonstrated a decrease in clinical events in the group which received bone marrow cells.
Investigators of this study decided to study CDCs because they come from a person's own body, and therefore have no foreign immune antigens which may be rejected. Since the cells come from the person's heart, they are more likely to form heart tissue. In addition, animal studies indicate no safety problems and that these cells are capable of forming heart muscle and blood vessel cells after heart attacks. The investigators are now studying whether the same is true in humans.
详细描述
The type of study that is being proposed is called a prospective, randomized, dose escalation study. This means that some of the patients will receive a solution which contains the cells and some of the patients will receive conventional medical treatment. The ratio is 2:1, which means that twice as many patients will receive cells as will receive conventional medical treatment. The first 6 patients in each group will be randomized to receive the study drug at a dose of 12.5 million cells or conventional medical treatment. The remaining 18 patients will be randomized to receive study drug at a dose of 25 million cells or conventional medical treatment. The DSMB will evaluate unblinded AE data (including SAEs) when the first six patients have been enrolled and those receiving cells have been discharged. There are two study sites. Each site will enroll 15 participants. The total number of subjects will be 30, with an approximate 20% attrition rate.
Subjects will be referred to participate in the study by physicians caring for them. The target number of participants is 24 patients who have an open artery to inject the stem cells and whose biopsy tissues have been grown to 12.5 million cells. If for some reason the cells cannot be expanded to 12.5 million or the subject's artery is not open enough to allow proper injection, the subject will be replaced in the study population of 24 patients but continue to be followed. This means that the subject will undergo all tests, procedures (except cell infusion) and follow-up visits that would have otherwise been required for participation in the study.
When a subject is determined to be eligible for the study, the protocol will be reviewed with the subject and informed consent will be obtained by a physician participating in the study prior to any testing or treatment.
This study is being conducted at the Cedars-Sinai Medial Center and The Johns Hopkins Hospital. The total length of a subject's participation in the study will be approximately 14 months, from enrollment to 12 month follow-up visit.
SCREENING PHASE - Participants will undergo a screening evaluation. A physical examination with medical history will be performed which includes medication review as well as alcohol or drug use. A blood specimen will be obtained, approximately three teaspoons, to assess for blood counts, chemistry, HIV, hepatitis and pregnancy test for females of childbearing age. An MRI scan will be performed to determine whether the portion of the heart from which the biopsy would be obtained was damaged from the heart attack. MRI will also detect if any cardiac tumors are present. An electrocardiogram will be performed to assess your heart's electrical activity. Additionally, a computed tomography (CT) scan of the chest, abdomen and pelvis will be performed to detect any existing cancer or tumors. If any of the tests are positive, the subject will not be able to participate in the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Non-cardiovascular disease with expected life expectancy of < 3 years.
- •Contraindications to MRI, including:
- •prior ICD placement
- •estimated glomerular filtration rate < 50 ml/min
- •known reaction to gadolinium
- •claustrophobia
- •pacemaker
- •ear implant, and cochlear implant.
- •History of possible presence of ferromagnetic material including programmable shunt, shrapnel, penile prosthesis, intra-uterine device, bullets, tattoos, artificial limb, blood vessel coil, and tissue expander may require special screening.
- •Septal infarction involving the right ventricular endocardium as demonstrated by screening MRI (because its presence might increase the potential risk of septal biopsy and decrease treatment benefit due to decreased viability of injured septal-based stem cells).
- •History of cardiac tumor, or cardiac tumor demonstrated on MRI.
- •Requirement for chronic immunosuppressive therapy.
- •Participation in an on-going protocol studying an experimental drug or device.
- •Diagnosis of right ventricular arrhythmogenic dysplasia.
- •Patients with occlusion of the infarct-related artery before administration of the study agent.
- •Current alcohol abuse.
- •Current drug abuse.
- •Pregnancy.
- •Child-bearing potential without use of effective contraception. Men intending to "father" children are also excluded.
- •Human Immunodeficiency virus infection.
- •Viral hepatitis.
- •Uncontrolled diabetes and/or hemoglobin A1C > 8.5%.
- •Abnormal liver function (SGPT > 3 times the upper reference range) and hematology (hematocrit < 25%, WBC < 3000, platelets < 100,000) studies without a reversible, identifiable cause.
- •Ventricular tachycardia or fibrillation not associated with an acute ischemic episode.
- •New York Heart Association Class 4 congestive heart failure.
- •Canadian Cardiovascular Society Angina Class 3 or
- •Evidence of tumor on screening chest/abdominal/pelvic (body) CT scan.
- •Symptomatic ventricular tachyarrhythmia complicating the index myocardial infarction.
- •Individuals who are not fluent in English.
结局指标
主要结局
The primary objective is to demonstrate the safety of autologous cardiosphere-derived stem cells administered by intra-coronary infusion in patients with ischemic left ventricular dysfunction and a recent myocardial infarction.
时间窗: 6 months
次要结局
- The secondary objective is to demonstrate the efficacy of autologous cardiosphere-derived cells administered by intra-coronary infusion in patients with ischemic left ventricular dysfunction and a recent myocardial infarction.(12 months)
研究者
Eduardo Marban, MD, PhD
Director
Cedars-Sinai Medical Center