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Effectiveness of Stem Cell Treatment for Adults With Ischemic Cardiomyopathy (The FOCUS Study)

Information source: The University of Texas Health Science Center, Houston
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Chronic Ischemic Heart Disease; Left Ventricular Dysfunction; Angina; Ischemic Cardiomyopathy

Intervention: Adult stem cells (Biological); Placebo (Biological)

Phase: Phase 2

Status: Completed

Sponsored by: The University of Texas Health Science Center, Houston

Official(s) and/or principal investigator(s):
Robert Simari, MD, Study Chair, Affiliation: Cardiovascular Cell Therapy Research Network


Coronary artery disease (CAD) is a common disorder that can lead to heart failure. Not all people with CAD are eligible for today's standard treatments. One new treatment approach uses stem cells—specialized cells capable of developing into other types of cells—to stimulate growth of new blood vessels for the heart. This study will determine the safety and effectiveness of withdrawing stem cells from someone's bone marrow and injecting those cells into the person's heart as a way of treating people with CAD and heart failure.

Clinical Details

Official title: Randomized, Controlled, Phase II, Double-Blind Trial of Intramyocardial Injection of Autologous Bone Marrow Mononuclear Cells Under Electromechanical Guidance for Patients With Chronic Ischemic Heart Disease and Left Ventricular Dysfunction

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome:

Change in Maximal Oxygen Consumption (VO2max)

Change in Left Ventricular End Systolic Volume (LVESV)as Assessed Via Echo

Change in Reversible Defect Size

Secondary outcome:

Regional Wall Motion by MRI (in Eligible Patients)

Regional Blood Flow Improvement by MRI (in Eligible Patients)

Regional Wall Motion by Echocardiography

Clinical Improvement in CCS Classification (Angina Pectoris)

Clinical Improvement in NYHA Classification

Number of Participants With a Decrease in Anti-anginal Medication

Exercise Time and Level

Serum BNP Levels in Patients With CHF

LV Diastolic Dimension

Incidence of a Major Adverse Cardiac Event

Reduction in Fixed Perfusion Defect(s)Via SPECT

Detailed description: Coronary artery disease (CAD), a disease in which blood vessels become clogged by a build-up of plaque, is the leading cause of heart failure, a condition in which the heart can no longer pump enough blood to the rest of the body. People with heart failure caused by CAD are said to have ischemic cardiomyopathy. Normal treatment for CAD involves coronary artery bypass grafting (in which a vein from another part of the body is grafted around an artery that has become blocked) or coronary angioplasty and stent placement (in which a blocked artery is opened and a small tube is placed to keep the artery open). However, some people with ischemic cardiomyopathy, such as those with substantial scar tissue on the heart wall or those with a particular heart structure, may not be eligible for these treatments. An alternative treatment being developed is therapeutic angiogenesis, which involves stimulating the growth of new blood vessels. Recent research has shown that withdrawing stem cells from bone marrow and implanting the cells into heart tissue may be an effective way to achieve therapeutic angiogenesis. This study will determine the safety and effectiveness of using stem cells to stimulate new blood vessel growth in the hearts of people with ischemic cardiomyopathy. Participation in this study, including follow-up visits and phone calls, will last 60 months. Participants will first undergo 3 to 4 days of screening procedures that will include a physical examination, multiple lab tests, and a battery of tests on heart health. Next, participants will be randomized to receive either active stem cell injections or placebo injections. The injections and related procedures will be performed in a hospital and last approximately 72 hours. During this time, participants in both groups will first undergo a bone marrow aspiration procedure. Participants receiving active stem cells will also undergo NOGA electromechanical cardiac mapping, which involves inserting a monitoring device through a catheter and into the heart. Injections of stem cells will then be made to 15 damaged sites on the heart through a special catheter. Participants receiving placebo injections will receive 15 injections of an inactive, saline-based solution. After the injection procedures, all participants will undergo two echocardiograms, an electrocardiogram, blood tests, and overnight monitoring in a telemetry unit. After the hospital stay, all participants will attend five study visits that will occur 1 week and 1, 3, 6, and 12 months after the injection procedures. At all study visits, participants will undergo an electrocardiogram, lab tests, and a review of adverse health events. On all but the last study visit, participants will have cardiac markers assessed, and they will wear a 24-hour Holter monitor to track heart activity. At the last three visits, participants will also complete quality of life questionnaires. All participants will then receive four follow-up telephone calls that will occur 2, 3, 4, and 5 years after the injection procedures.


Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.


Inclusion Criteria:

- Patients >18 years of age with significant coronary heart disease not amenable to


- Left ventricular dysfunction (LVEF) less than or equal to 45%, measured by

echocardiogram; limiting angina (Class II to IV); and/or congestive heart failure (CHF), NYHA class II to III

- Receiving maximal medical therapy, defined as a medical regimen that includes the

maximal tolerated dose of at least two antiangina medications, such as beta-blockers, nitrates, or calcium-channel blockers

- Presence of a defect, as identified by single photon emission computed tomography

(SPECT) isotope protocol, or viability, as identified by NOGA electromechanical cardiac mapping system

- Coronary artery disease not well suited to any other type of revascularization

procedure in the target region of the ventricle, as determined by a cardiovascular surgeon and interventional cardiologist who are not investigators in the trial

- Hemodynamic stability, as defined by systolic blood pressure of at least 80 mm Hg

without intravenous pressors or support devices

- Females of childbearing potential must be willing to use two forms of birth control

for the duration of the study Exclusion Criteria:

- Atrial fibrillation or flutter without a pacemaker that guarantees a stable heart


- Unstable angina

- Left ventricular (LV) thrombus, as documented by echocardiography or LV angiography

- A vascular anatomy that precludes cardiac catheterization

- Severe valvular disease or mechanical aortic valve that precludes safe entry of the

catheter into the left ventricle

- Pregnant or lactating

- Platelet count less than 100,000 per mm3

- White blood cell count less than 2,000 per mm3

- Revascularization within 30 days of consent

- Transient ischemic attack or stroke within 60 days of study consent

- Implantable cardioverter-defibrillator shock within 30 days of baseline consent, and

within 30 days of randomization

- Presence of ventricular tachycardia lasting 30 seconds or more on 24-hour Holter

monitor or electrocardiogram (ECG) performed during screening period

- Bleeding diathesis, defined as an international normalized ratio of at least 2. 0 in

the absence of warfarin therapy

- A history of malignancy in the last 5 years excluding basal cell carcinoma, that has

been surgically removed, with proof of surgical clean margins

- Has a known history of HIV, has active hepatitis B or active hepatitis C

- Any condition requiring immunosuppressive medication

- High-risk acute coronary syndrome (ACS) or a myocardial infarction in the month prior

to consent

- A left ventricular wall thickness of <8 mm (by echocardiogram) of the infero-lateral

wall at the target site for cell injection.

- Inability to walk on a treadmill, except for class IV angina patients, who will be

evaluated separately

- Enrolled in an investigational device or drug study within the previous 30 days

- Hepatic dysfunction, as defined as aspartate aminotransferase (AST) or alanine

aminotransferase (ALT) more than 1. 5 times the upper limit of normal range prior to study entry

- Chronic renal insufficiency, defined as a serum creatinine level greater than 2. 5

mg/dL or requiring dialysis

- Any other condition that in the judgment of the investigator would be a

contraindication to enrollment or follow-up

Locations and Contacts

University of Florida-Department of Medicine, Gainesville, Florida 32611, United States

Minneapolis Heart Institute Foundation, Minneapolis, Minnesota 55407, United States

Cleveland Clinic, Cleveland, Ohio 44195, United States

Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States

Texas Heart Institute, Houston, Texas 77225, United States

Additional Information

Click here for more information on the Cardiovascular Cell Therapy Research Network

Click here for more information on the National Institutes of Health Stem Cell Basics

Click here for more information on the National Heart, Lung, and Blood Institute

Click here for more information on the Indiana Center for Vascular Biology and Medicine

Related publications:

Gee AP, Richman S, Durett A, McKenna D, Traverse J, Henry T, Fisk D, Pepine C, Bloom J, Willerson J, Prater K, Zhao D, Koç JR, Ellis S, Taylor D, Cogle C, Moyé L, Simari R, Skarlatos S. Multicenter cell processing for cardiovascular regenerative medicine applications: the Cardiovascular Cell Therapy Research Network (CCTRN) experience. Cytotherapy. 2010 Sep;12(5):684-91. doi: 10.3109/14653249.2010.487900.

Willerson JT, Perin EC, Ellis SG, Pepine CJ, Henry TD, Zhao DX, Lai D, Penn MS, Byrne BJ, Silva G, Gee A, Traverse JH, Hatzopoulos AK, Forder JR, Martin D, Kronenberg M, Taylor DA, Cogle CR, Baraniuk S, Westbrook L, Sayre SL, Vojvodic RW, Gordon DJ, Skarlatos SI, Moyé LA, Simari RD; Cardiovascular Cell Therapy Research Network (CCTRN). Intramyocardial injection of autologous bone marrow mononuclear cells for patients with chronic ischemic heart disease and left ventricular dysfunction (First Mononuclear Cells injected in the US [FOCUS]): Rationale and design. Am Heart J. 2010 Aug;160(2):215-23. doi: 10.1016/j.ahj.2010.03.029.

Zierold C, Carlson MA, Obodo UC, Wise E, Piazza VA, Meeks MW, Vojvodic RW, Baraniuk S, Henry TD, Gee AP, Ellis SG, Moyé LA, Pepine CJ, Cogle CR, Taylor DA. Developing mechanistic insights into cardiovascular cell therapy: Cardiovascular Cell Therapy Research Network Biorepository Core Laboratory rationale. Am Heart J. 2011 Dec;162(6):973-80. doi: 10.1016/j.ahj.2011.05.024.

Starting date: March 2009
Last updated: June 2, 2015

Page last updated: August 23, 2015

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