A Phase I/II, Randomized, Double-Blinded, Placebo-Controlled Study of the Safety and Efficacy of Intramyocardial Injection of Autologous Human Mesenchymal Stem Cells (MSCs) in Patients With Chronic Ischemic Left Ventricular Dysfunction Secondary to Myocardial Infarction (MI) Undergoing Cardiac Surgery for Coronary Artery Bypass Grafting (CABG)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 9
- 试验地点
- 4
- 主要终点
- Number of Patients With Serious Adverse Events
研究概览
简要总结
Heart attacks are a leading cause of death in both men and women in the United States. When a person has a heart attack, blood is unable to reach a certain area of the heart, and if the blood supply is not re-established quickly, that area of the heart can suffer permanent damage. While recovery from a heart attack can be managed through medications and lifestyle changes, these treatments can not reverse the original damage to the heart. Current research is focusing on the development of cell-based therapies using stem cells to repair organs that have been irreversibly damaged by disease. A specific form of stem cells, called adult mesenchymal stem cells (MSCs), has shown promise for heart repair. This study will evaluate the safety and effectiveness of injecting MSCs into the heart to repair and restore heart function in people who have had a heart attack and who are having heart surgery for coronary artery bypass grafting (CABG).
详细描述
Participation in this study will last 18 months. Potential participants will undergo initial screening 5 to 7 weeks prior to CABG surgery. Screening will include a physical exam, blood draw, pregnancy test, questions about medical history, current medications, and alcohol or drug use, an electrocardiogram (ECG), magnetic resonance imaging (MRI) of the heart, questionnaires, an echocardiogram and a computed tomography (CT) scan. Eligible participants will then undergo two baseline visits within 6 weeks of their scheduled surgery. Baseline Visit 1 will consist of vital sign measurements, a bone marrow aspiration to obtain MSCs and a blood draw for a biomarker test. Baseline Visit 2 will include treadmill test, 6-minute walk test, pulmonary function (FEV1) study and a 48 Hour Ambulatory ECG. After the second baseline visit, participants will be assigned randomly to receive either MSCs or placebo after surgery.
On the day of surgery, once all of the bypass grafts have been placed, a high or low dose of MSCs or placebo will be injected into a damaged area of the heart that did not receive a bypass graft. After receiving the injections, participants will remain in the hospital for up to 7 days. During this stay, participants will undergo a daily blood draw, urine test, ECG, and ambulatory ECG monitoring for the first 96 hours after surgery.
Upon being discharged, participants will return for monthly visits for 6 months and for follow-up visits 12 and 18 months after surgery. These visits will repeat most initial screening and baseline tests. There will be one additional visit 14 days after surgery, which will include questions about side effects, a physical exam, and a 48-hour ambulatory ECG.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 21 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of chronic ischemic heart failure caused by a heart attack
- •Scheduled to undergo cardiac surgery for CABG
- •Ejection fraction between 15% and 50%
- •Presence of an akinetic or dyskinetic region by standard imaging
排除标准
- •Glomerular filtration rate of less than 50 mL/min/1.73m2 at study entry
- •Contraindication to performance of an MRI scan
- •Bone marrow dysfunction, as evidenced by a 20% or more deviation from normal hematocrit, white blood cell count, or platelet values without another explanation
- •A coagulopathy condition not due to a reversible cause (i.e., Coumadin)
- •Known, serious radiographic contrast allergy
- •Known allergies to penicillin or streptomycin
- •Organ transplant recipient
- •Clinical history of malignancy within 5 years of study entry (e.g., patients with prior malignancy must be disease free for 5 years), except curatively treated basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma
- •Non-cardiac condition that limits lifespan to less than 1 year
- •On chronic therapy with immunosuppressant medication
- •Serum positive for HIV, hepatitis B, or hepatitis C
- •Female who is pregnant, nursing, or of child-bearing potential and not practicing effective birth control methods
研究组 & 干预措施
Lower dose mesenchymal stem cell (MSC) injection
Participants will receive lower dose mesenchymal stem cell injections for a total of 2 x 10^7 cells
干预措施: Lower dose mesenchymal stem cell (MSC) injection (Biological)
Higher dose MSC injection
Participants will receive higher dose of mesenchymal stem cell injections for a total of 2 x 10^8 cells
干预措施: Higher dose MSC injection (Biological)
(3) Placebo
Participants will receive placebo injections
干预措施: Placebo (Genetic)
结局指标
主要结局
Number of Patients With Serious Adverse Events
时间窗: 12 Months
Six-month post-CABG surgery serious adverse event (SAE) proportion of patients experiencing a composite of sustained ventricular arrhythmias, (lasting longer than 15 seconds), with hemodynamic compromise, sudden unexpected death at six months, ectopic tissue formation at 12 months by chest/abdomen/pelvis CT exam.
次要结局
- Left Ventricular Function (LVF) in Region of MSC Injection(Assessed at Baseline and 18 Months)
- Change in Peak Volume Oxygen(Baseline, 6 Months, 18 Months)
- Change in NYHA Functional Class(Baseline to 6 Months, 6 months to 18 Months)
- Change in Left Ventricular End Diastolic and Systolic Volume(Baseline, 6 Months, 18 Months)
- Change in Six Minute Walk Test(Baseline, 6 Months, 18 Months)
- Minnesota Living With Heart Failure Questionnaire Scores(Assessed at 6 Months and 18 Months)
- Incidence of Major Adverse Cardiac Events (MACE)(18 Months)
- Number of Participants With Abnormal 48-Hour Ambulatory ECG Recordings(Assessed at 6 Months, 12 Months, and 18 Months)
- Regional Left Ventricular Wall Thickening(Assessed at Baseline and 18 months)
- Change in Pulmonary Function(Baseline, 6 Months, 12 Months, 18 Months)
- Change in Infarct Scar Size (ISS) Over 18 Month Period(Baseline, 6 Months, 18 Months)
- Left Ventricular End Diastolic Wall Thickness(Assessed at Baseline and 18 months)
- Change in Left Ventricular Ejection Fraction(Baseline to 6 Months, Baseline to 18 Months)
- Serial Troponin Values (ng/mL)(Assessed at Baseline, 12 hours, 24 hours, 36 hours, and 48 hours post CABG)
- Creatinine Kinase - Muscle/Brain (MB) (ng/mL)(Assessed at Baseline, 12 Hours, 24 Hours, 36 Hours, and 48 hours post CABG)
- Rate of Treatment Emergent Adverse Events(Assessed at 6 Months, 12 Months, and 18 Months)
- Number of Clinically Significant Laboratory Values(18 Months)
- Number of Abnormal Echocardiogram Readings 2 Days Post CABG.(Day 2)
研究者
Joshua M Hare
Director, Interdisciplinary Stem Cell Institute
University of Miami