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
Summary
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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Patients >18 years of age with significant coronary heart disease not amenable to
revascularization.
- 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
rate
- 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
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