Autologous Stem Cells for Cardiac Angiogenesis (FOCUS HF)

Randomized Controlled Single Blind Trial of Autologous Bone Marrow Mononuclear Cells Under Electromechanical Guidance for Therapeutic Angiogenesis

This is a phase 1, single-blind trial to evaluate using autologous bone marrow mononuclear stem cells in ischemic cardiomyopathy patients. The patients must have a Left Ventricular Ejection Fraction (LVEF) of less than or equal to 45%. Once the patient meets all inclusion criteria, and no exclusion criteria are found, the subject is consented for the study, and extensive baseline testing is performed at St Luke's Hospital in Houston. Once all baseline testing criteria is met, the patient has their own bone marrow harvested and later that day the subject is taken to a cardiac catheterization lab where left ventricular electromechanical mapping using NOGA software (NOGA mapping) is performed and the processed stem cells are injected under electromechanical guidance into the affected areas of the left ventricle. The patient is usually discharged home the next day and returns for follow up visits at weeks 1, 2, 4, 6, 8, 12, months 6 and 12 and for phone call follow-up at months 4, 5, 7, 8, 9, 10, 11. Patients undergo extensive testing at most of these follow-up visits, including repeat cardiac catheterization with NOGA mapping at month 6 after stem cell injection.

Study Overview

• Status: Completed
• Conditions: Ischemic Cardiomyopathy
• Intervention / Treatment: Device: Intramyocardial Injection of stem cells via NOGA Mapping; Other: Control, then Stem Cell Therapy

Detailed Description

This is a phase 1, single-blind trial to evaluate the use of autologous bone marrow mononuclear stem cells in ischemic cardiomyopathy patients. The study hypothesis is that transendocardial injections of autologous mononuclear bone marrow cells in patients with end-stage ischemic heart disease is safe, can promote neovascularization, and can improve perfusion and myocardial contractility. The primary object of this study will be to evaluate the safety of autologous-bone-marrow mononuclear cell injections. The secondary endpoint of the study is to assess the efficacy of autologous bone marrow cells in improving cardiac contractile function and functional outcome. The efficacy will be assessed on the basis of the treadmill Max VO2 (maximum volume oxygen uptake). Secondarily the efficacy will be assessed on the basis of clinical status and imaging rests, with follow-up extending to 1 year after enrollment.A maximum of 30 patients will be enrolled in the study. At the end of the 6-month visit. after the required angiogram with mapping and non-invasive testing is complete, the patients will be told whether they were in the control or the active group (stem cell therapy). Those in the control group will be told before final invasive testing, and those who consent may cross over to the active therapy arm and undergo the cell injection procedure (control, then stem cell therapy. In these patients, the foll-up angiogram and mapping procedure will also serve as the baseline procedure required for cell injection. Bone marrow mononuclear cells will be injected in an identical fashion, according to the same criteria described for the original treatment group, and these patients will have identical follow-up visits starting again at the baseline time-point and extending for up to 1 year.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Heart Institute/Baylor St. Luke's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• LVEF less than 45%
• Functional class III or IV angina
• At least 7% reversibility by Single Photon Emission Computed Tomography (SPECT) nuclear study
• there are additional inc. criteria

Exclusion Criteria:

• AGe <18 or >70 years of age
• Constant atrial fibrillation
• Left ventricular (LV) thrombus
• History of malignancy in the last 5 years
• LV wall thickness of < 8 mm at the target site
• there are additional exclusion criteria

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stem Cell Therapy; Subject is randomized to receive Stem Cell Therapy (intramyocardial injection of stem cells) via NOGA mapping.	Device: Intramyocardial Injection of stem cells via NOGA Mapping; Subject is randomized to receive intramyocardial injection of stem cells (stem cell therapy) via NOGA mapping to deliver cells in the active arm of the protocol.; Other Names: NOGA Star catheter and Myostar Injection.
Other: Control, then Stem Cell Therapy; Subject is randomized to receive a NOGA mapping and no injections at time of active enrollment. At 6 months, subject is offered stem cell therapy.	Other: Control, then Stem Cell Therapy; Subject is randomized to receive a NOGA mapping and no injections (sham treatment)at time of active enrollment and treatment then offered stem cell therapy at 6 months.; Other Names: cross-over

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of Autologous-bone-marrow Injections	Safety of cell injections was assessed by reviewing adverse events at 3 time points: (1) up to 2 weeks post-procedure), (2) 3 months post-procedure, and (3) at 6 months post-procedure. Major adverse events were adjudicated (hospitalization, arrhythmia, exacerbation of congestive HF [CHF], acute coronary syndrome, myocardial infarction, stroke, or death).	up to 2 weeks post-procedure, 3 months and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Canadian Cardiovascular (CCS) Angina Score	Clinical and functional assessment in endstage ischemic cardiomyopathy patients using Canadian Cardiovascular (CCS) Angina Score which indicates discomfort from angina (chest pain). Class I- Angina only during strenuous or prolonged activity Class II- Slight limitation, with angina only during vigorous physical activity Class III- Symptoms with everyday living activities (moderate limitation) Class IV- Inability to perform any activity without angina or angina at rest (severe limitation)	baseline, 3 months and 6 months
New York Heart Association (NYHA)Classification	Clinical and functional assessment in endstage ischemic cardiomyopathy patients using New York Heart Association (NYHA)Classification and indicates extent of heart failure based on limitations in physical activity. Class I- No symptoms/limitation in ordinary physical activity (shortness of breath when walking, etc) Class II-Mild symptoms/slight limitation during ordinary activity Class III- Marked limitation in activity due to symptoms, even during less-than-ordinary activity Class IV- Severe limitations in activity/experiences symptoms while at rest (bedbound)	baseline, 3 months and 6 months
Myocardial Oxygen Consumption (MVO2)	Clinical and functional assessment in endstage ischemic cardiomyopathy patients using Myocardial Oxygen Consumption (MVO2)which is the amount of oxygen used by the heart muscle and is indicative of heart muscle function. Normal value is 15.5 Volume %. Measured as milliliters (ml) oxygen per kilogram (kg) body weight per minute.	baseline, 3 months and 6 months
Echocardiography (EF)Percent (%)	Clinical and functional assessment in endstage ischemic cardiomyopathy patients using Echocardiography measures ejection fraction(EF)as a percentage(%) of blood leaving the heart with each beat or contraction. It can provide information concerning structural characteristics and blood flow in the heart and blood vessels. A normal heart pumps 50-75% of the blood with each contraction.	baseline, 3 months and 6 months
Minute Ventilation- Carbon Dioxide Production Relationship (VE/VCO2 Slope)	Clinical and functional assessment in endstage ischemic cardiomyopathy patients using Minute Ventilation- Carbon Dioxide Production Relationship (VE/VCO2 slope)measure during a cardiopulmonary exercise test has a high prognostic value for survival in heart failure patients. Normal VE (milliliters per minute)/VCO2 (milliliters per minute)equals 25.	baseline and 3 months
Echocardiography Wall Motion Score Index (WMSI)	Clinical and functional assessment in endstage ischemic cardiomyopathy patients using Echocardiography Wall Motion Score Index (WMSI)which allows detection of abnormalities in the heart wall or blood flowing through the heart. Normal contracting Left Ventricle has WMSI of 1. Larger WMSI indicates higher degree of abnormalities (2 for hypokinetic, 3 for akinetic, 4 for dyskinetic, and 5 for aneurysmal). WMSI was calculated as the sum of scores divided by the total number of segments.	baseline and 3 months
Single-photon Emission Computed Tomography (SPECT) Imaging for Left Ventricular Ejection Fraction (LVEF) Percentage (%)	Clinical and functional assessment in endstage ischemic cardiomyopathy patients using Single-photon emission computed tomography (SPECT) imaging for Left Ventricular Ejection Fraction (LVEF) percentage (%)to determine how well the heart is pumping blood from the left ventricle. Different method for evaluating how much (%) of blood is pumped through heart with each contraction.	baseline, 3 months and 6 months
Angiography Left Ventricular Ejection Fraction (LVEF) Percent (%)	Clinical and functional assessment in endstage ischemic cardiomyopathy patients using angiography left ventricular ejection fraction (LVEF) percent (%) which is an invasive method used to estimate how well the heart is pumping blood through the ventricle and is considered the "gold" standard.	baseline and 6 months
Left Ventricular End-Diastolic Volume (LVEDV)	Clinical and functional assessment in endstage ischemic cardiomyopathy patients using Left Ventricular End-Diastolic Volume (LVEDV)which is the volume of blood inside the left ventricle when the heart has completed its filling cycle. The volume of the left ventricle is measured during contraction and relaxation. Normal heart volume inside the left ventricle is about 140 milliliters.	baseline, 3 months and 6 months
Left Ventricular End-Systolic Volume (LVESV) (ml)	Clinical and functional assessment in endstage ischemic cardiomyopathy patients using Left Ventricular End-Systolic Volume (LVESV)when the blood moves from the ventricles to the atria during the contraction cycle. Measured as volume in milliliters (ml). Normal is approximately 60- 65 milliliters.	baseline, 3 months and 6 months
Endocardial Unipolar Voltages (UPV)	Clinical and functional assessment in endstage ischemic cardiomyopathy patients using Endocardial Unipolar Voltages (UPV)in millivolts(mV)which may be indicative of scar tissue. Normal is <5.5 mV.	baseline and 6 months
Linear Local Shortening (LLS)	Clinical and functional assessment in endstage ischemic cardiomyopathy patients using Linear Local Shortening (LLS)which is an indicator of mechanical properties of the heart and measured as a percentage (%)of local contraction.	baseline and 6 months

Collaborators and Investigators

• Sponsor: Texas Heart Institute
• Collaborators: CHI St. Luke's Health, Texas
• Investigators: Principal Investigator: Emerson Perin, MD,PhD., Texas Heart Institute/Baylor St Luke's Medical Center

Publications and helpful links

General Publications

• Perin EC, Silva GV, Henry TD, Cabreira-Hansen MG, Moore WH, Coulter SA, Herlihy JP, Fernandes MR, Cheong BY, Flamm SD, Traverse JH, Zheng Y, Smith D, Shaw S, Westbrook L, Olson R, Patel D, Gahremanpour A, Canales J, Vaughn WK, Willerson JT. A randomized study of transendocardial injection of autologous bone marrow mononuclear cells and cell function analysis in ischemic heart failure (FOCUS-HF). Am Heart J. 2011 Jun;161(6):1078-87.e3. doi: 10.1016/j.ahj.2011.01.028. Epub 2011 May 10.

Helpful Links

• Stem Cell Group at Texas Heart Institute

Study record dates

Study Major Dates

• Study Start: April 1, 2004
• Primary Completion (Actual): August 1, 2008
• Study Completion (Actual): November 1, 2009

Study Registration Dates

• First Submitted: September 12, 2005
• First Submitted That Met QC Criteria: September 12, 2005
• First Posted (Estimate): September 20, 2005

Study Record Updates

• Last Update Posted (Estimate): November 28, 2016
• Last Update Submitted That Met QC Criteria: October 17, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Autologous; Transplant; Cardiac; Stem Cell
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Cardiomyopathies
• Other Study ID Numbers: HSC-MS-04-141

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Data summarized and published. No need to share individual patient data.