临床试验/NCT02501811

NCT02501811已完成2 期

A Phase II, Randomized, Placebo-Controlled Study of the Safety, Feasibility, & Efficacy of Autologous Mesenchymal Stem Cells & C-kit+ Cardiac Stem Cells, Alone or in Combination, Administered Transendocardially in Subjects With Ischemic HF

The University of Texas Health Science Center, Houston14 个研究点分布在 1 个国家目标入组 125 人开始时间: 2015年10月1日最近更新: 2021年4月26日

适应症

试验速览

阶段: 2 期
状态: 已完成
发起方: The University of Texas Health Science Center, Houston
入组人数: 125
试验地点: 14
主要终点: Change From Baseline in Left Ventricular Ejection Fraction (LVEF)

研究概览研究设计入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This is a phase II, randomized, placebo-controlled clinical trial designed to assess feasibility, safety, and effect of autologous bone marrow-derived mesenchymal stem cells (MSCs) and c-kit+ cells both alone and in combination (Combo), compared to placebo (cell-free Plasmalyte-A medium) as well as each other, administered by transendocardial injection in subjects with ischemic cardiomyopathy.

详细描述

This is a randomized, placebo-controlled clinical trial designed to evaluate the feasibility, safety, and effect of Combo, MSCs alone, and c-kit+ cells alone compared with placebo as well as each other in subjects with heart failure of ischemic etiology. Following a successful lead-in phase, a total of one hundred forty-four (144) subjects will be randomized (1:1:1:1) to receive Combo, MSCs, c-kit+ cells, or placebo. After randomization, baseline imaging, relevant harvest procedures, and study product injection, subjects will be followed up at 1 day, 1 week, 1 month, 3 months, 6 months and 12 months post study product injection. All subjects will receive study product injection (cells or placebo) using the NOGA® XP Mapping and Navigation System. Subjects will have delayed-enhanced magnetic resonance imaging (DEMRI) scans to assess scar size and LV function and structure at baseline and at 6 and 12 months post study product administration. All endpoints will be assessed at the 6 and 12 month visits which will occur 180 ±30 days and 365 ±30 days respectively from the day of study product injection (Day 0). For the purpose of the endpoint analysis and safety evaluations, the Investigators will utilize an "intention-to-treat" study population, however an as treated analysis will also be conducted.

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: 21 Years 至 79 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•Be ≥ 21 and <80 years of age
•Have documented coronary artery disease (CAD) with evidence of myocardial injury, LV dysfunction, and clinical evidence of HF
•Have a "detectable" area of myocardial injury defined as ≥ 5% LV involvement (infarct volume) and any subendocardial involvement by cMRI
•Have an EF ≤ 40% by cMRI
•Be receiving guideline-driven medical therapy for heart failure at stable and tolerated doses for ≥ 1 month prior to consent. For beta-blockade "stable" is defined as no greater than a 50% reduction in dose or no more than a 100% increase in dose.
•Be a candidate for cardiac catheterization
•Have NYHA class I, II, or III heart failure symptoms
•If a female of childbearing potential, be willing to use one form of birth control for the duration of the study, and undergo a pregnancy test at baseline and within 36 hours prior to injection

排除标准

•Indication for standard-of-care surgery (including valve surgery, placement of left-ventricular assist device, or imminent heart transplantation), coronary artery bypass grafting (CABG) procedure, and/or percutaneous coronary intervention (PCI) for the treatment of ischemic and/or valvular heart disease. Subjects who require or undergo PCI should undergo these procedures a minimum of 3 months in advance of randomization. Subjects who require or undergo CABG should undergo these procedures a minimum of 4 months in advance of randomization. In addition, subjects who develop a need for revascularization following enrollment should undergo revascularization without delay. Indication for imminent heart transplantation is defined as a high likelihood of transplant prior to collection of the 12 month study endpoint. Candidates cannot be UNOS status 1A or 1B, and they must have documented low probability of being transplanted
•Valvular heart disease including 1) mechanical or bioprosthetic heart valve; or 2) severe (any valve) insufficiency/regurgitation within 12 months of consent
•Aortic stenosis with valve area ≤ 1.5 cm2
•History of ischemic or hemorrhagic stroke within 90 days of consent
•History of a left ventricular remodeling surgical procedure utilizing prosthetic material
•Presence of a pacemaker and/or implantable cardioverter-defibrillator (ICD) generator with any of the following limitations/conditions:
•manufactured before the year 2000
•leads implanted < 6 weeks prior to consent
•non-transvenous epicardial, or abandoned leads
•subcutaneous ICDs
•leadless pacemakers
•any other condition that, in the judgment of device-trained staff, would deem an MRI contraindicated
•Pacemaker-dependence with an ICD (Note: pacemaker-dependent candidates without an ICD are not excluded)
•A cardiac resynchronization therapy (CRT) device implanted less than 3 months prior to consent
•Other MRI contraindications (e.g. patient body habitus incompatible with MRI)
•An appropriate ICD firing or anti-tachycardia pacing (ATP) for ventricular fibrillation or ventricular tachycardia within 30 days of consent
•Ventricular tachycardia ≥ 20 consecutive beats without an ICD within 3 months of consent, or symptomatic Mobitz II or higher degree atrioventricular block without a functioning pacemaker within 3 months of consent
•Presence of LV thrombus
•Evidence of active myocarditis
•Baseline maximal oxygen consumption (VO2 max) greater than 75% of age and gender based predictive values
•Baseline eGFR <35 ml/min/1.73m2
•Blood glucose levels (HbA1c) >10%
•Hematologic abnormality evidenced by hematocrit < 25%, white blood cell < 2,500/ul or platelet count < 100,000/ul
•Liver dysfunction evidenced by enzymes (AST and ALT) ˃ 3 times the upper limit of normal (ULN)
•Coagulopathy (INR ≥ 1.3) not due to a reversible cause (e.g., warfarin and/or Factor Xa inhibitors). Subjects who cannot be withdrawn from anticoagulation will be excluded.
•HIV and/or active hepatitis B virus (HBV) or hepatitis C virus (HCV)
•Allergy to radiographic contrast material that cannot adequately be managed by premedication
•Known history of anaphylactic reaction to penicillin or streptomycin
•Received gene or cell-based therapy from any source within the previous 12 months
•History of malignancy within 5 years (i.e., subjects with prior malignancy must be disease free for 5 years), excluding basal cell carcinoma and cervical carcinoma in situ which have been definitively treated
•Condition that limits lifespan to < 1 year
•History of drug abuse (illegal "street" drugs except marijuana, or prescription medications not being used appropriately for a pre-existing medical condition) or alcohol abuse (≥ 5 drinks/day for ˃ 3 months), or documented medical, occupational, or legal problems arising from the use of alcohol or drugs within the past 24 months
•Participation in an investigational therapeutic or device trial within 30 days of consent
•Cognitive or language barriers that prohibit obtaining informed consent or any study elements
•Pregnancy or lactation or plans to become pregnant in the next 12 months
•Any other condition that, in the judgment of the Investigator or Sponsor, would impair enrollment, study product administration, or follow-up

结局指标

主要结局

Change From Baseline in Left Ventricular Ejection Fraction (LVEF)

时间窗: Baseline to 6 months

Change in left ventricular ejection fraction as assessed via cardiac MRI

Change From Baseline in Global Strain (HARP MRI)

时间窗: Baseline to 6 months

Change in global circumferential strain as assessed via cardiac MRI

Change From Baseline in Regional Strain (HARP MRI)

时间窗: Baseline to 6 months

Change in regional longitudinal strain as assessed via cardiac MRI

Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVI)

时间窗: Baseline to 6 months

Change in left ventricular end diastolic volume index as measured via cardiac MRI

Change From Baseline in Left Ventricular End Systolic Volume Index (LVESVI)

时间窗: Baseline to 6 months

Change in left ventricular end systolic volume index as assessed via cardiac MRI

Change From Baseline in Left Ventricular Sphericity Index

时间窗: Baseline to 6 months

Change in left ventricular sphericity as assessed via cardiac MRI. Sphericity index is the ratio of the long and short axis measurements of the left ventricle.

Change From Baseline in Scar Size Percent (DEMRI)

时间窗: Baseline to 6 months

Change in scar size percent as assessed via cardiac MRI

Change From Baseline in Scar Tissue Mass (DEMRI)

时间窗: Baseline to 6 months

Change in scar tissue mass as assessed via cardiac MRI

Change From Baseline in Maximal Oxygen Consumption (Peak VO2)

时间窗: Baseline to 6 months

Change in maximal oxygen consumption (peak V02) as assessed via treadmill

Change From Baseline in Exercise Tolerance (Six Minute Walk Test)

时间窗: Baseline to 6 months

Change in distance walked (in meters) as measured by the 6 minute walk test. Two walk tests were completed at each endpoint visit (separated by 30 minutes). The average distance of the two walk tests was used for analysis.

Change From Baseline in Minnesota Living With Heart Failure Questionnaire (MLHFQ) Score

时间窗: Baseline to 6 months

Change in the quality of life summary score as measured by the Minnesota Living with Heart Failure Questionnaire. Minimum and maximum scores for the scale are 0 and 105 respectively. Lower scores indicative of better outcomes.

Change From Baseline in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP)

时间窗: Baseline to 6 months

Change in N-Terminal pro-Brain Natriuretic Peptide (NT-proBNP) as measured via laboratory blood draw

Change From Baseline in Left Ventricular Ejection Fraction (LVEF)-Trajectory