Autologous Stem Cells for Cardiac Angiogenesis (FOCUS HF)

• ClinicalTrials.gov Identifier: NCT00203203
• Recruitment Status: Completed
• First Posted: September 20, 2005
• Results First Posted: January 30, 2013
• Last Update Posted: November 28, 2016
• Sponsor: Texas Heart Institute
• Collaborator: CHI St. Luke's Health, Texas
• Information provided by (Responsible Party): Emerson Perin, MD, PhD, Texas Heart Institute

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Ischemic Cardiomyopathy	Device: Intramyocardial Injection of stem cells via NOGA Mapping; Other: Control, then Stem Cell Therapy	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Randomized Controlled Single Blind Trial of Autologous Bone Marrow Mononuclear Cells Under Electromechanical Guidance for Therapeutic Angiogenesis
• Study Start Date: April 2004
• Actual Primary Completion Date: August 2008
• Actual Study Completion Date: November 2009

Arms and Interventions

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 Name: NOGA Star catheter and Myostar Injection.
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 Name: cross-over

Outcome Measures

Primary Outcome Measures :

1. Safety of Autologous-bone-marrow Injections [ Time Frame: up to 2 weeks post-procedure, 3 months and 6 months ]
   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).

Secondary Outcome Measures :

1. Canadian Cardiovascular (CCS) Angina Score [ Time Frame: baseline, 3 months and 6 months ]

   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)

2. New York Heart Association (NYHA)Classification [ Time Frame: baseline, 3 months and 6 months ]

   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)

3. Myocardial Oxygen Consumption (MVO2) [ Time Frame: baseline, 3 months and 6 months ]
   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.
4. Echocardiography (EF)Percent (%) [ Time Frame: baseline, 3 months and 6 months ]
   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.
5. Minute Ventilation- Carbon Dioxide Production Relationship (VE/VCO2 Slope) [ Time Frame: baseline and 3 months ]
   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.
6. Echocardiography Wall Motion Score Index (WMSI) [ Time Frame: baseline and 3 months ]
   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.
7. Single-photon Emission Computed Tomography (SPECT) Imaging for Left Ventricular Ejection Fraction (LVEF) Percentage (%) [ Time Frame: baseline, 3 months and 6 months ]
   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.
8. Angiography Left Ventricular Ejection Fraction (LVEF) Percent (%) [ Time Frame: baseline and 6 months ]
   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.
9. Left Ventricular End-Diastolic Volume (LVEDV) [ Time Frame: baseline, 3 months and 6 months ]
   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.
10. Left Ventricular End-Systolic Volume (LVESV) (ml) [ Time Frame: baseline, 3 months and 6 months ]
    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.
11. Endocardial Unipolar Voltages (UPV) [ Time Frame: baseline and 6 months ]
    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.
12. Linear Local Shortening (LLS) [ Time Frame: baseline and 6 months ]
    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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Texas

Texas Heart Institute/Baylor St. Luke's Medical Center

Houston, Texas, United States, 77030

Sponsors and Collaborators

Texas Heart Institute

CHI St. Luke's Health, Texas

Investigators

• Principal Investigator: Emerson Perin, MD,PhD.; Texas Heart Institute/Baylor St Luke's Medical Center

More Information

Additional Information:

Stem Cell Group at Texas Heart Institute 

Publications of Results:

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.

• Responsible Party: Emerson Perin, MD, PhD, Director Clinical Research for Cardiovascular Medicine and Director Stem Cell Center, Texas Heart Institute
• ClinicalTrials.gov Identifier: NCT00203203
• Other Study ID Numbers: HSC-MS-04-141
• First Posted: September 20, 2005
• Results First Posted: January 30, 2013
• Last Update Posted: November 28, 2016
• Last Verified: October 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Data summarized and published. No need to share individual patient data.

Keywords provided by Emerson Perin, MD, PhD, Texas Heart Institute:

Autologous; Cardiac; Stem Cell; Transplant

Additional relevant MeSH terms:

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases