LVAD Therapy: Exploring the Effect of Intramyocardial Injection of Mesenchymal Precursor Cells on Myocardial Function
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 30
- 试验地点
- 21
- 主要终点
- Intervention Related Adverse Events
研究概览
简要总结
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. 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. In addition, this research is being done to test whether injecting the MPCs into the heart is effective in improving heart function.
详细描述
Intramyocardial injection of mesenchymal precursor cells (MPC) in patients with advanced heart failure who are treated with left ventricular assist device (LVAD) implantation may result in a renewable source of proliferating functional cardiomyocytes, as well as induce development of capillaries and larger size blood vessels to supply oxygen and nutrients to endogenous myocardium and newly-implanted cardiomyocytes, and release factors capable of paracrine signaling. If safety is established and an efficacy signal is observed in this exploratory trial, then the investigators will design a follow-up trial (stage 2) based on an adaptive design. The next trial would randomize patients to active therapy at one of two doses (25 and 75 million MPCs) versus placebo, and based on a predetermined selection criterion drop randomization to one of the dose arms as results accrue. Should this exploratory trial demonstrate safety but no signal of efficacy, then the subsequent trial would be based on a single dose of 75 million MPCs versus placebo.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent, inclusive of release of medical information, and Health Insurance Portability and Accountability Act (HIPAA) documentation;
- •Age 18 years or older;
- •If the subject 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 procedure;
- •Female subjects of childbearing potential must have a negative serum pregnancy test at screening;
- •Admitted to the clinical center at the time of randomization;
- •Clinical indication and accepted candidate for implantation of an FDA approved implantable, non-pulsatile LVAD as a bridge to transplantation or for destination therapy.
排除标准
- •Planned percutaneous LVAD implantation;
- •Anticipated requirement for biventricular mechanical support;
- •Cardiothoracic surgery within 30 days prior to randomization;
- •Myocardial infarction within 30 days prior to randomization;
- •Prior cardiac transplantation, LV reduction surgery, or cardiomyoplasty;
- •Acute reversible cause of heart failure (e.g. myocarditis, profound hypothyroidism);
- •Stroke within 30 days prior to randomization;
- •Platelet count < 100,000/ul within 24 hours prior to randomization;
- •Active systemic infection within 48 hours prior to randomization;
- •Presence of >10% anti-human leukocyte antigen (anti-HLA) antibody titers with known specificity to the MPC donor HLA antigens;
- •A 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);
- •Received investigational intervention within 30 days prior to randomization;
- •Treatment and/or an incompleted follow-up treatment of any investigational cell based therapy within 6 months prior to randomization;
- •Active participation in other research therapy for cardiovascular repair/regeneration;
- •Prior recipient of stem precursor cell therapy for cardiac repair;
- •Pregnant or breastfeeding at time of randomization.
结局指标
主要结局
Intervention Related Adverse Events
时间窗: 90 days
The primary safety endpoint of this study is the incidence of the following potential study-intervention related adverse events within 90 days post intervention (LVAD implantation + intramyocardial injection of study product): infectious myocarditis, myocardial rupture, neoplasm, hypersensitivity reaction, and immune sensitization.
次要结局
- Functional Status and Ventricular Function(90 days)
研究者
Deborah Ascheim
Associate Professor, Clinical Director of Research, InCHOIR
Icahn School of Medicine at Mount Sinai