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

NCT00824005 | Completed Phase 2 Results DMC

• 3 other identifiers: 580U01HL0873181 U01-HL-087318-01 (Project 3)
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

Chronic Ischemic Heart Disease; Left Ventricular Dysfunction; Angina; Ischemic Cardiomyopathy

Keywords

Congestive Heart Failure; Regional Wall Motion; Perfusion Defects

Outcome Measures

Primary Outcomes (3)

• Change in Maximal Oxygen Consumption (VO2max)

  The VO2(max) is assessed using the Naughton treadmill protocol.

  Measured at Baseline and Month 6

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

  Echocardiographic measurements were performed by an echocardiographic core laboratory. LVESVs were calculated by the modified biplane Simpson method, using myocardial contrast to enhance endocardial definition. To account for patient body surface area, LVESV indices are reported.

  Measured at Baseline and Month 6

• Change in Reversible Defect Size

  Adenosine myocardial perfusion (SPECT) tests were collected at baseline and 6 months to identify change in ischemic (reversible) defects. SPECT imaging was performed at rest and after adenosine infusion over 4 minutes. To enhance the detection of viability on resting images, sublingual nitroglycerin was administered 15 minutes before injecting technetium Tc 99m sestamibi for the resting image.

  Measured at Baseline and Month 6

Secondary Outcomes (11)

• Regional Wall Motion by MRI (in Eligible Patients)

  Measured at Baseline and Month 6

• Regional Blood Flow Improvement by MRI (in Eligible Patients)

  Measured at Baseline and Month 6

• Regional Wall Motion by Echocardiography

  Measured at Baseline and Month 6

• Clinical Improvement in CCS Classification (Angina Pectoris)

  Measured at Baseline and Month 6

• Clinical Improvement in NYHA Classification

  Measured at Baseline and Month 6

Study Arms (2)

Placebo Injections

PLACEBO COMPARATOR

Participants will receive placebo injections.

Biological: Placebo

Active Stem Cell Injections

EXPERIMENTAL

Participants will receive active stem cell injections.

Biological: Adult stem cells

Interventions

Adult stem cells BIOLOGICAL

Single procedure of intramyocardial electromechanical-guided injection of approximately 100 million bone marrow mononucleated cells (BM-MNCs), administered in 15 different injection sites

Also known as: Adult autologous stem cells, Bone marrow mononucleated cells

Active Stem Cell Injections

Placebo BIOLOGICAL

Single procedure of intramyocardial electromechanical-guided needle insertions and injection of 5% human serum albumin and saline in 15 different injection sites

Also known as: Human serum albumin, HSA

Placebo Injections

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Cardiovascular Cell Therapy Research Network (CCTRN): collaborator

Study Sites (5)

University of Florida-Department of Medicine

Gainesville, Florida, 32611, United States

Location

Minneapolis Heart Institute Foundation

Minneapolis, Minnesota, 55407, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Texas Heart Institute

Houston, Texas, 77225, United States

Location

Related Publications (5)

• Gee AP, Richman S, Durett A, McKenna D, Traverse J, Henry T, Fisk D, Pepine C, Bloom J, Willerson J, Prater K, Zhao D, Koc JR, Ellis S, Taylor D, Cogle C, Moye 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.

  PMID: 20524773 BACKGROUND

• 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, Moye 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.

  PMID: 20691824 BACKGROUND

• Zierold C, Carlson MA, Obodo UC, Wise E, Piazza VA, Meeks MW, Vojvodic RW, Baraniuk S, Henry TD, Gee AP, Ellis SG, Moye 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.

  PMID: 22137069 BACKGROUND

• Perin EC, Willerson JT, Pepine CJ, Henry TD, Ellis SG, Zhao DX, Silva GV, Lai D, Thomas JD, Kronenberg MW, Martin AD, Anderson RD, Traverse JH, Penn MS, Anwaruddin S, Hatzopoulos AK, Gee AP, Taylor DA, Cogle CR, Smith D, Westbrook L, Chen J, Handberg E, Olson RE, Geither C, Bowman S, Francescon J, Baraniuk S, Piller LB, Simpson LM, Loghin C, Aguilar D, Richman S, Zierold C, Bettencourt J, Sayre SL, Vojvodic RW, Skarlatos SI, Gordon DJ, Ebert RF, Kwak M, Moye LA, Simari RD; Cardiovascular Cell Therapy Research Network (CCTRN). Effect of transendocardial delivery of autologous bone marrow mononuclear cells on functional capacity, left ventricular function, and perfusion in chronic heart failure: the FOCUS-CCTRN trial. JAMA. 2012 Apr 25;307(16):1717-26. doi: 10.1001/jama.2012.418. Epub 2012 Mar 24.

  PMID: 22447880 RESULT

• Cogle CR, Wise E, Meacham AM, Zierold C, Traverse JH, Henry TD, Perin EC, Willerson JT, Ellis SG, Carlson M, Zhao DX, Bolli R, Cooke JP, Anwaruddin S, Bhatnagar A, da Graca Cabreira-Hansen M, Grant MB, Lai D, Moye L, Ebert RF, Olson RE, Sayre SL, Schulman IH, Bosse RC, Scott EW, Simari RD, Pepine CJ, Taylor DA; Cardiovascular Cell Therapy Research Network (CCTRN). Detailed analysis of bone marrow from patients with ischemic heart disease and left ventricular dysfunction: BM CD34, CD11b, and clonogenic capacity as biomarkers for clinical outcomes. Circ Res. 2014 Oct 24;115(10):867-74. doi: 10.1161/CIRCRESAHA.115.304353. Epub 2014 Aug 18.

  PMID: 25136078 DERIVED

Related Links

• Click here for more information on the Cardiovascular Cell Therapy Research Network
• Click here for more information on the National Heart, Lung, and Blood Institute

MeSH Terms

Conditions

Ventricular Dysfunction, Left; Angina Pectoris; Heart Failure

Interventions

Serum Albumin, Human

Condition Hierarchy (Ancestors)

Ventricular Dysfunction; Heart Diseases; Cardiovascular Diseases; Myocardial Ischemia; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Serum Albumin; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Blood Proteins

Limitations and Caveats

Sample size was small and required large improvements in order to show significant treatment effects. SPECT often underestimates reversibility and viability in those with multivessel disease. Presence of cardiac devices limited MRI evaluation.

Results Point of Contact

• Title: Lemuel Moye, MD, PhD
• Organization: UT-Houston School of Public Health

Lemmoye@msn.com

713-500-9518

Study Officials

• Robert Simari, MD

  Cardiovascular Cell Therapy Research Network

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor - School of Public Health

Study Record Dates

• First Submitted: January 15, 2009
• First Posted: January 16, 2009
• Study Start: March 1, 2009
• Primary Completion: November 1, 2011
• Study Completion: May 1, 2012
• Last Updated: July 1, 2015
• Results First Posted: April 4, 2013

Record last verified: 2015-06

Locations

US (5)