Phase I/II Randomized Clinical Trial to Assess the Safety and Feasibility of Transendocardial Injection of Bone Marrow Autologous Mesenchymal Stem Cells in Patients With Idiopathic Dilated Cardiomyopathy.
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 70
- 试验地点
- 3
- 主要终点
- Major adverse cardiac adverse events. SAEs and AEs.
研究概览
简要总结
The purpose of this study is to assess the safety, the feasibility and the efficacy of transendocardial injection of bone marrow-derived mesenchymal stem cells (MSCs) in patients with dilated idiopathic cardiomyopathy.
详细描述
Chronic congestive heart failure (CHF) is a public health problem that entails high rates of morbidity and mortality, and enormous costs for health systems worldwide. In the United States there are 5 million people living with CHF, and each year 60.000 people reach terminal phases of the disease, with mortality rates of 70-80% at two years. Although the first cause of CHF in developed countries is atherosclerotic coronary artery disease (CAD), dilated idiopathic cardiomyopathy (DCM) represents almost half of the cases of newly diagnosed CHF. Treatment of CHF includes pharmacological and non-pharmacological strategies, including implantable cardioverter defibrillators, cardiac resynchronization therapy and heart transplantation. Despite all these advances, CHF prognosis remains poor. Cardiac stem cell therapy emerged more than ten years ago as a new hope for CHF patients.
Although the most extensive evidence of the benefits of stem cell therapy for cardiovascular diseases refers to ischemic heart disease (CAD), initial experiences with stem cells for other conditions such as DCM are encouraging.
This randomized clinical trial will include 70 patients with DCM, left ventricular ejection fraction (LVEF) between 20% and 45%, and who are symptomatic in New York Heart Association (NYHA) functional class II-III/IV. In a first-in-man pilot phase, 10 patients will be treated with transendocardial injections of bone marrow-derived MSCs after cardiac catheterization and NOGA XPTM mapping of the left ventricle. A Data and Safety Monitoring Board (DSMB) will analyse the safety and feasibility of this first phase of the trial, and then 60 patients more will be randomized to receive MSCs or placebo (ratio 3:1).
Primary objectives include safety and feasibility variables, and secondary objectives include efficacy variables. All patients will be studied with a complete cardiac imaging protocol that includes: electrocardiography, echocardiography, treadmill tests with oxygen consumption, holter, laboratory analyses, magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), electromechanical mapping (NOGA XPTM) and quality of life questionnaires.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •II-III NYHA functional class, under optimal medical therapy.
- •LVEF ≥ 20% and ≤ 45% by echocardiography, SPECT or left ventriculogram one month prior to enrollment.
- •Anterior wall thickness ≥ 8 mm by echocardiography or MRI one month prior to enrollment.
- •Idiopathic DCM diagnosis (having excluded CAD, valvular heart disease, cardiac toxic drugs, tachyarrhythmias, metabolic diseases, systemic diseases, infectious diseases) six months prior to enrollment.
- •Patients rejected for heart transplantation should have been discussed in the Heart Team at their respective centres, and a document stating the reason for exclusion will be kept in the medical record.
- •Able to exercise on a treadmill, MVO2 between ≥ 12 and ≤ 21 ml/Kg/min.
- •Hemodynamic stability (blood pressure > 100/40 mmHg, heart rate < 110 bpm and oxygen saturation > 95%).
- •Negative pregnancy test in women.
- •Signed informed consent
排除标准
- •Evidence of secondary dilated cardiomyopathy causes: CAD, valvular heart disease, cardiac toxic drugs, tachyarrhythmias, metabolic diseases, systemic diseases, infectious diseases, myocarditis or postpartum ventricular dysfunction.
- •Permanent atrial fibrillation.
- •Candidates for ICD or CRT devices. Patients with theses devices can be enrolled if the device has been implanted at least 6 months before inclusion, and only if no-response has been observed to CRT.
- •Candidates for heart transplantation if surgery is anticipated in the next 2 years.
- •Left ventricular thrombus by echocardiography, MRI or left ventriculogram.
- •Peripheral artery disease that precludes cardiac catheterization with 8 Fr sheaths. .
- •Anterior wall thickness < 8 mm by echocardiography or MRI one month prior to enrollment.
- •Chronic renal failure (creatinine > 2,5 mg/dL).
- •I or IV NYHA functional class. Cardiogenic shock is defined as systolic blood pressure < 90 mmHg with no response to fluids, or < 100 mmHg with inotropes and without bradycardia.
- •Previous history of drug abuse (alcohol, etc...).
- •Acute or chronic infectious disease (including B/C hepatitis and HIV).
- •Pregnancy or child-bearing period.
- •MRI contraindications: pacemakers, ICD, metalic prosthesis, etc.
- •Bleeding or coagulation disorders (INR > 2 without anticoagulation treatment).
- •Cancer history 5 years prior to enrollment.
- •Life expectancy less than 1 year.
- •Any disease or condition that the investigator finds decisive for exclusion
结局指标
主要结局
Major adverse cardiac adverse events. SAEs and AEs.
时间窗: change from enrollment( 1, 3, 6, 12, 18 and 24 months)
Major adverse cardiac adverse events includes cerebral adverse events
Incidence of complications with the use of NOGA XPTM catheters.
时间窗: Change from enrolment( 1, 3, 6, 12, 18, 24 months)
NYHA functional class.
时间窗: Change from enrolment( 1, 3, 6, 12, 18, 24 months)
Laboratory parameters including C-reactive protein an brain natriuretic peptide
时间窗: Change from enrolment( 1, 3, 6, 12, 18, 24 months)
次要结局
- Max.oxygen consumption(MVO2),functional capacity.(6,12,24 months)
- LVEF(left ventriculogram, electromech. mapping parameters(NOGA XPTM))(12 months)
- Quality of life questionnaires(6,12 and 24 months)
- Extension. of perfusion defects(MRI/SPECT).(6 and 24 months)
- LVEF, ventricular vol.,wall motion score index(echocard./MRI/SPECT(6,12 and 24 months)
- NYHA Functional Class(1, 3, 6, 12, 18, 24 months)