Clinical trial NCT00314366: Intramyocardial Injection of Autologous Aldehyde Dehydrogenase-Bright Stem Cells for Therapeutic Angiogenesis (FOCUS Br)
Official title: Phase IB Randomized Controlled Double-Blind Trial of Intramyocardial Injection of Autologous Aldehyde Dehydrogenase-Bright Stem Cells Under Electromechanical Guidance for Therapeutic Angiogenesis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Coronary Artery Disease
Keywords: stem cell
autologous
ischemia
Lead sponsor: Texas Heart Institute
Sponsor class: OTHER
Collaborators: name: CHI St. Luke's Health, Texas
name: Aldagen
First posted: 2006-04-13
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety of Aldehyde Dehydrogenase Bright Stem Cells Versus the Control Group as Measured by Combined Early and Late Adverse Events
timeFrame: Baseline and 6 months
Secondary outcomes:
measure: New York Heart Association (NYHA) Classification
timeFrame: Baseline and 6 months
measure: Canadian Cardiovascular (CCS) Angina Score
timeFrame: Baseline and 6 months
measure: Echocardiography (EF)Percent (%)
timeFrame: Baseline and 6 months
measure: Left Ventricular End-Systolic Volume (LVESV) (ml)
timeFrame: baseline and 6 months
measure: Left Ventricular End-Diastolic Volume (LVEDV)
timeFrame: baseline and 6 months
measure: Echocardiography Wall Motion Score Index (WMSI)
timeFrame: baseline and 6 months
measure: Myocardial Oxygen Consumption (MVO2)
timeFrame: baseline and 6 months
measure: Echocardiography (EF) Percent (%)
timeFrame: baseline and 6 months
measure: Total Severity Score (Stress)
timeFrame: baseline and 6 months
measure: Total Severity Score (Rest)
timeFrame: baseline and 6 months
measure: Total Severity Score (Reversible)
timeFrame: baseline and 6 months
Other outcomes:
Locations:
city: Houston
country: United States
facility: Texas Heart Institute/Baylor St. Luke's Medical Center
state: Texas
Study officials:
affiliation: Texas Heart Institute
name: Emerson Perin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.