Use of Adult Autologous Stem Cells in Treating People 2 to 3 Weeks After Having a Heart Attack (The Late TIME Study)

Study Overview
=================
Brief Summary
-----------------
More than 1 million Americans suffer heart attacks each year. Although current treatments are able to stabilize the condition of the heart, none is able to restore heart function as it was prior to the heart attack. Adult stem cells, which are immature cells that can become many different types of cells, may offer a potential means of reversing or preventing permanent damage caused by a heart attack. Recent studies have shown promise in using adult stem cells from bone marrow to reverse damage to the heart muscle caused by a heart attack, but more research is needed to assess the safety and effectiveness of stem cell use and to discover the best time to administer treatment. This study will evaluate the safety and effectiveness of using adult stem cell infusions 2 to 3 weeks after a heart attack for improving heart function in people who have had a recent heart attack and a common procedure called a percutaneous coronary intervention (PCI).

Detailed Description
-----------------
Heart attacks are a leading cause of death for both men and women in the United States. A heart attack occurs when blood flow to the heart is restricted, commonly due to a blood clot that has formed in one of the coronary arteries. If the clot becomes large enough, blood flow to the heart can be blocked almost completely and the heart muscle in that area can suffer permanent injury or death. Although a PCI can be used to open up the blocked artery and restore blood flow to the heart muscle, there may be a significant amount of heart tissue that has been irreversibly damaged. Recent studies have shown that adult stem cells from bone marrow may be able to improve heart function after a heart attack. These specialized cells may have the ability to promote blood vessel growth, prevent cell death, and transform themselves into a number of tissues, including muscle. After an acute heart attack, a remodeling process is initiated in the heart in an attempt to compensate for damaged areas. Consequently, the condition of the heart muscle several weeks after a heart attack may differ considerably from the heart's condition during the acute setting. For some patients, delaying the delivery of the stem cells until 2 to 3 weeks after a heart attack may be better than initiating treatment during the acute phase. This study will evaluate the safety and effectiveness of placing adult stem cells into injured heart muscle 2 to 3 weeks after a heart attack for improving heart function in people who have had a recent heart attack and a PCI. Participation in this study will last 24 months. All participants will first undergo baseline assessments that will include a medical history, a physical exam, an electrocardiogram (ECG), blood draws, an echocardiogram, and a magnetic resonance imaging (MRI) test. Participants will then be assigned randomly to receive stem cells or placebo between 2 and 3 weeks after their heart attack. The morning of the stem cell or placebo infusion, participants will undergo a blood draw and a bone marrow aspiration procedure of the hip bone to collect the stem cells. Later the same day, either stem cells or placebo will be infused through a catheter and into the damaged area of the heart. For the first 24 hours after the infusion, participants will be asked to wear a small ECG machine called a Holter monitor. Participants will also be asked to record their temperature twice a day for a month after the infusion. Participants will return for follow-up visits at Months 1, 3, 6, 12, and 24 and will repeat many of the baseline assessments.

Official Title
-----------------
A Phase II, Randomized, Controlled, Double-Blind Pilot Trial Evaluating the Safety and Effect of Administration of Bone Marrow Mononuclear Cells Two to Three Weeks Following Acute Myocardial Infarction

Conditions
-----------------
Left Ventricular Dysfunction

Intervention / Treatment
-----------------
* Biological: Adult stem cells
* Biological: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria Patients at least 21 years of age. Patients with first acute MI and subsequent successful primary percutaneous coronary intervention (PCI) in an artery at least 2.5 mm in diameter occurring two to three weeks before recruitment. No contraindications to undergoing cell therapy procedure within two to three weeks following AMI and PCI. Hemodynamic stability as defined as no requirement for IABP, inotropic or blood pressure supporting medications. Ejection fraction following reperfusion with PCI <=45% as assessed by echocardiography. Consent to protocol and agree to comply with all follow-up visits and studies. Women of child bearing potential willing to use an active form of birth control. Exclusion criteria Patients will be excluded from the study if they meet any of the following conditions: History of sustained ventricular arrhythmias not related to their AMI (evidenced by previous holter monitoring and/or medication history for sustained ventricular arrhythmias in patient's medical chart). Require CABG or PCI due to the presence of residual coronary stenosis >70% luminal obstruction in the non-infarct related vessel (Additional PCI of non-culprit vessels may be performed prior to enrollment). History of any malignancy within the past five years excluding non-melanoma skin cancer or cervical cancer in-situ. History of chronic anemia (hemoglobin (Hb) <9.0 mg/dl). History of thrombocytosis (platelets >500k). History of thrombocytopenia in the absence of recent evidence that platelet counts are normal Known history of elevated INR (PT) or PTT. Life expectancy less than one year. History of untreated alcohol or drug abuse. Currently enrolled in another Investigational drug or device trial Previous CABG. Previous MI resulting in LV dysfunction (LVEF <55%) History of stroke or transient ischemic attack (TIA) within the past six months. History of severe valvular heart disease (aortic valve area <1.0 cm2 or >3+ mitral regurgitation). Pregnancy or breast feeding Subjects with a known history of HIV, or has active hepatitis B, active hepatitis C, or active tuberculosis (TB) Patients with active inflammatory or autoimmune disease on chronic immunosuppressive therapy. Contraindications to cMRI. Previous radiation to the pelvis with white blood cell count (WBC) and platelet counts below hospital specific normal values. Women child bearing potential not willing to practice an active form of birth control. Chronic liver disease that might interfere with survival or treatment with cell therapy. Chronic renal insufficiency as defined by a creatinine ≥2.0 mg/dL or requires chronic dialysis.

Ages Eligible for Study
-----------------
Minimum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Participants will receive active stem cell infusion 2 to 3 weeks after a percutaneous coronary intervention (PCI). | Biological: Adult stem cells<br>* One time infusion of approximately 150 million total nucleated cells (TNC) in 30 ml of 5% HSA/saline solution<br>* Other names: Bone marrow mononucleated cells;|
| Placebo Comparator: 2<br>Participants will receive placebo infusion (5% human serum albumin [HSA]) 2 to 3 weeks after a PCI. | Biological: Placebo<br>* One time infusion of 30 ml of HSA (5%)<br>* Other names: HSA;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global Left Ventricular Function | Left ventricular ejection fraction (global) as assessed via cardiac MRI. Values reported represent the change in Global EF from baseline to six months. | Measured at Baseline and Month 6 | 
| Regional Left Ventricular Function (Infarct Zone Wall Motion) | One of two calculated values of regional left ventricular function as assessed via cardiac MRI. The infarct zone is defined as the cMRI segments with the largest 2 signal intensity enhancement measures with gadolinium (using a 17-segment model).Values reported represent the change in wall motion over time in the infarct zone from baseline to six months. | Measured at Baseline and Month 6 | 
| Regional Left Ventricular Function (Border Zone Wall Motion) | Two of two calculated values of regional left ventricular function assessed via cardiac MRI. The border zone is defined as those regions adjacent to the infarct zone in which the cMRI signal intensity enhancement were in the 10%-75% range. Values reported represent the change in wall motion over time in the border zone of the infarct from baseline to six months. | Measured at Baseline and Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Combined Endpoint | Combined endpoint: first of death, reinfarction, repeat revascularization, and hospitalization for heart failure. This is measured as the number of events by treatment group over the 6 month follow up period. | Measured at Baseline and Month 6 | 
| Left Ventricular Mass | Left ventricular mass (LV mass. Values reported represent the change in LV mass from baseline to six months.) | Measured at Baseline and Month 6 | 
| End Diastolic Volume Index | Left ventricular end diastolic volume index. Values reported represent the change in LV end diastolic index from baseline to six months. | Measured at Baseline and Month 6 | 
| End Systolic Volume Index | Left ventricular end systolic volume index. Values reported represent the change in LV end systolic volume index from baseline to six months. | Measured at Baseline and Month 6 | 
| Infarct Volume | Infarct volume(mL). Values reported represent the change in infarct volume from baseline to six months. | Measured at Baseline and Month 6 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Acute Myocardial Infarction, Global Left Ventricular Ejection Fraction, Regional Left Ventricular Ejection Fraction, Left Ventricular Mass, Infarct Size, End Systolic Volume, End Diastolic Volume