Intramyocardial Injection of Autologous Aldehyde Dehydrogenase-Bright Stem Cells for Therapeutic Angiogenesis (FOCUS Br)

Phase IB Randomized Controlled Double-Blind Trial of Intramyocardial Injection of Autologous Aldehyde Dehydrogenase-Bright Stem Cells Under Electromechanical Guidance for Therapeutic Angiogenesis

Recent studies have suggested that it may be possible to grow new blood vessels (angiogenesis) to supply the heart muscle that is currently not getting enough blood. One theory is that a certain type of stem cell, aldehyde dehydrogenase bright stem cells, may stimulate the growth of new vessels. After a bone marrow procedure, the special cells are separated and then injected back into the heart around the area of damage with a special guidance and injection system.

Once a patient meets all inclusion criteria and no exclusion criteria, he/she will be consented to the study and extensive baseline testing will be completed at St. Luke's Episcopal Hospital in Houston, Texas. Once all baseline criteria are met, the patient has his/her own bone marrow harvested and later injected, if randomized to receive active treatment. The day after the bone marrow harvest, the patient is taken to the cardiac catheterization lab where NOGA mapping is performed and the processed cells or placebo 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 at weeks 1 and 4, and months 3 and 6, and at one year unless there is a crossover and then he/she begins baseline again at 6 months and follow-up for one more year. Follow-up testing, including quality of life and NOGA mapping, is done at the time of injection, as well as at 6 months.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Biological: Stem Cell Therapy; Other: Control (plasma)

Detailed Description

This is a phase I, double blind trial to evaluate the use of Aldehyde Dehydrogenase-Bright (ALDHbr) in ischemic cardiomyopathy patients. The study hypothesis is that transendocardial injections of autologous bone marrow cells in patients with end-stage ischemic heart disease is safe, can provide neovascularization, and can improve perfusion and myocardial contractility. The primary object of this study is to assess the safety of the ALDHbr cell injections. The efficacy will be based upon treadmill MVO2. A maximum of 60 patients will be enrolled in the study. At the end of 6 months, after the required testing has been completed, the patients will be told whether they were in the control group or not. The patients in the control group will be given the option to crossover and actually receive stem cell injection. At the time of crossover, which then becomes the baseline, patients will begin the follow-up with all testing including clinic visits for one year for a total of 18 months follow-up.

• Study Type: Interventional
• Enrollment (Actual): 21
• 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

Description

Inclusion Criteria:

• Canadian cardiovascular (CV) Class II-IV angina and/or congestive heart failure (CHF) symptoms
• Ejection fraction less than or equal to 45%
• Reversible perfusion defect on single photon emission computed tomography (SPECT)
• Coronary artery disease (CAD) unable to be corrected by surgery (bypass) or intervention (stent)
• Able to walk on treadmill
• Hemodynamically stable

Exclusion Criteria:

• Age less than 18 or greater than 70
• Atrial fibrillation
• Severe valve disease
• History of cancer in last 5 years
• HIV positive; hepatitis B or C positive.
• Left ventricular wall thickness less than 8 mm
• Recent heart attack within the last 30 days

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Stem Cell Therapy; Subjects are randomized to receive Stem Cell Therapy (treatment) at the time of enrollment where cells are delivered after NOGA mapping and cells injected with the Myostar catheter.	Biological: Stem Cell Therapy; Cells are injected under electromechanical guidance and delivered by the Myostar catheter after NOGA mapping.; Other Names: NOGA Myostar catheter
Placebo Comparator: Control; Placebo patients will receive injections of plasma (control) instead of stem cells. Placebo patients are able to crossover and receive active treatment at 6 months if they meet the criteria. At 6 months, subject is offered stem cell therapy and then followed for 12 months.	Other: Control (plasma); Placebo patients receive an injection of plasma (control) containing 5 % albumin the the same quantity as the stem cell arm. A total of 15 injections of 0.2 ml to total 3.0 ml.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of Aldehyde Dehydrogenase Bright Stem Cells Versus the Control Group as Measured by Combined Early and Late Adverse Events	Safety of cell injections was assessed by reviewing adverse events at 2 time points: Baseline (periprocedural period up to 2 weeks post-procedure) and 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).	Baseline and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 and 6 months
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 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 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 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 and 6 months
Echocardiography Wall Motion Score Index (WMSI)	Clinical and functional assessment in endstage ischemic cardiomyopathy patients using Echocardiography Wall Motion Score Index (WMSI) as defined by the American Heart Association which allows detection of abnormalities in the heart wall or blood flowing through the heart. Using this model, the left ventricle is divided into 17 segments. 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 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 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 and 6 months
Total Severity Score (Stress)	For the stress test, cardiac SPECT polar mapping (gated dual-isotope) is used to evaluate perfusion, compared against a database with a statistically significant number of polar maps of healthy hearts based on gender, data acquisition method, stress vs rest and type of data (i.e. perfusion, wall motion or wall thickening) using a clinically validated software package (J Nucl Med Technol 2006; 34:3-17). The basal and mid-ventricle heart wall is mapped by cylindrical sampling and apex mapped by spheric, cylindric and radial sampling. Total severity score during stress is the sum of blackout pixels in the blackout polar map of myocardial perfusion during stress using cardiac SPECT imaging (adding scores in different views), weighted by the number of SDs below the mean. Total severity score varies from 0 (normal) to several thousands although the upper limit is not well defined. A score greater than 1000 indicates poor perfusion.	baseline and 6 months
Total Severity Score (Rest)	For the total severity score at rest, cardiac SPECT polar mapping (gated dual-isotope) is used to evaluate myocardial cardiac perfusion, compared against a database with a statistically significant number of polar maps of healthy hearts and compared based on gender, data acquisition method, stress vs rest and type of data (i.e. perfusion, wall motion or wall thickening) using a clinically validated software package (J Nucl Med Technol 2006; 34:3-17). The basal and mid-ventricle heart wall is mapped by cylindrical sampling and apex mapped by spheric, cylindric and radial sampling at rest. Total severity score at rest is the sum of blackout pixels in the rest blackout polar map of myocardial perfusion cardiac SPECT imaging (adding scores in different views), weighted by the number of SDs below the mean. Total severity score varies from 0 (normal) to several thousands although the upper limit is not well defined. A score greater than 1000 indicates poor perfusion.	baseline and 6 months
Total Severity Score (Reversible)	For the severity test, cardiac SPECT polar mapping (gated dual-isotope) is used to evaluate myocardial cardiac perfusion, compared against a database with a statistically significant number of polar maps of healthy hearts and compared based on gender, data acquisition method, stress vs rest and type of data (i.e. perfusion, wall motion or wall thickening) using clinically validated software package (J Nucl Med Technol 2006; 34:3-17). The basal and mid-ventricle heart wall is mapped by cylindrical sampling and apex mapped by spheric, cylindric and radial sampling at rest/stress. Total severity score is the sum of blackout pixels in rest/stress blackout polar map of myocardial perfusion cardiac SPECT imaging (adding scores in different views), weighted by number of SDs below mean. Total severity score reversible is total severity scores at rest subtracted from those during stress. The severity score varies from 0 (normal) to > 1000 (poor perfusion) but upper limit is not well defined.	baseline and 6 months

Collaborators and Investigators

• Sponsor: Texas Heart Institute
• Collaborators: Aldagen; CHI St. Luke's Health, Texas
• Investigators: Principal Investigator: Emerson Perin, MD, PhD, Texas Heart Institute

Publications and helpful links

General Publications

• Perin EC, Silva GV, Zheng Y, Gahremanpour A, Canales J, Patel D, Fernandes MR, Keller LH, Quan X, Coulter SA, Moore WH, Herlihy JP, Willerson JT. Randomized, double-blind pilot study of transendocardial injection of autologous aldehyde dehydrogenase-bright stem cells in patients with ischemic heart failure. Am Heart J. 2012 Mar;163(3):415-21, 421.e1. doi: 10.1016/j.ahj.2011.11.020. Epub 2012 Feb 10.

Helpful Links

• The link is to Texas Heart Institute's Stem Cell Department home page.

Study record dates

Study Major Dates

• Study Start: April 1, 2006
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): August 24, 2023

Study Registration Dates

• First Submitted: April 10, 2006
• First Submitted That Met QC Criteria: April 11, 2006
• First Posted (Estimated): April 13, 2006

Study Record Updates

• Last Update Posted (Estimated): April 23, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: stem cell; ischemia; autologous
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease
• Other Study ID Numbers: UT-H-GEN-05-0599

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Relevant results are summarized and published. No need for individual results to be shared.