Cardiomyopathy, Cardiovascular Disease, Heart Disease, Myocardial Disease, Myocardial Ischemia
Conditions
Keywords
Cardiovascular Disease, Cardiomyopathy, Heart Disease, Myocardial Disease, Myocardial Ischemia
Brief summary
The purpose of this study is to see if taking a cholesterol lowering drug Lipitor (Atorvastatin Calcium)will increase the number of endothelial progenitor cells (EPC's) circulating in the blood of heart failure patients taking this cholesterol-lowering drug, and if this will also show an improvement in the damaged areas of the patient's hearts as documented by MRI scans.
Detailed description
This study involves the testing of blood for cholesterol levels and flow cytometry tests to count the number of EPC's in your blood. These tests are routinely performed to gain knowledge about a person's health. If any incidental findings are identified as a result of your participation in this research study, you will be notified and referred to your doctor or appropriate health care professional. You are being asked to provide a blood sample that will be used to determine the usual numbers of EPC's circulating in the blood of healthy people who have no risk factors for heart disease. Your results will be compared with those of patients who have heart failure. Flow cytometry is a special laboratory test that can count, separate, and detect characteristics of cells in blood. Your blood sample will be analyzed using flow cytometry. Endothelial progenitor cells (EPC's) are immature cells that are necessary for new blood vessel formation. EPC's will be separated by flow cytometry and counted. You will not be given the results of your flow cytometry study.
Interventions
DRUGAtorvastatin Calcium
Atorvastatin Calcium starting at a 10 mg dose and may be increased up to 40 mg dose until cholesterol is lowered to an acceptable range. Blood will drawn every 2 weeks for the first 12 weeks to check the cholesterol level and adjust medication dosage. Cardiac MRI will be performed at the beginning and at the end of the 6 month study to measure the physical changes of the heart.
Sponsors
Pfizer
Philip Binkley
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Ischemic Cardiomyopathy (as defined above) with ejection fraction \< 35% * Non-ischemic Cardiomyopathy with ejection fraction \< 35% * NCEP ATPIII indication for therapy with a statin drug * No statin therapy within previous 6 months of study enrollment * Prescribed stable doses of standard heart failure therapies including beta blocking agents, angiotensin converting enzyme inhibitors or angiotensin receptor blockers, and diuretic agents as required
Exclusion criteria
* Pregnant or lactating * Myocardial infarction within 6 months preceding study enrollment * Primary valvular heart disease * Surgical or catheter based revascularization within the preceding 6 months * Documented viral or inflammatory myocarditis or cardiomyopathy * Peripartum cardiomyopathy * Infiltrative cardiomyopathies * Chemotherapy associated cardiomyopathy * Without indication for statin therapy * Contraindication to statin therapy including hepatic dysfunction, history of rhabdomyolysis or prior intolerance of statin therapy * Contraindication to magnetic resonance imaging
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Endothelial Progenitor Cells | Baseline - 6 months | Change in Endothelial Progenitor Cells (EPC) was assessed by extracting white blood cells from blood samples and labeling the white blood cells using the ALDEFLOUR system. Facscan analysis was then performed first isolating lymphocytic and monocytic cell lines, which contain the EPC populations, using forward versus side scatter plots. These cells were then scanned for fluorescence in the ALDEFLUOR frequency range allowing enumeration of progenitor cell lines. The measures of fluorescent cells was compared to numbers of unstained cells having the same back scatter range to correct for any background fluorescence. |
| Percentage Aldofluor Positive Cells | Baseline - 6 months | The primary outcome measure is the percentage of cells of total analyzed that are positive for the Aldofluor assay. This commercially available assay tests cells for the enzyme aldehyde dehydrogenase that is expressed in stem cells and other early life cycle undifferentiated cells. It thus provides a measure of circulating primordial cells or cells that may serve as progenitors of destination mature cells. The percentages are designed from Facscan analysis of prepared blood cells and are quantified by quadrants defined by specific fluorescent bands and cell size distribution. The quantification of cells thus defined in the four quadrants is automatically determined by software resident in the facscan analysis system. |
Countries
United States
Participant flow
Recruitment details
Patients were eligible for enrollment if they had dilated cardiomyopathy w/ an established ejection fraction \< 35% on a nonischemic or ischemic basis. All pts had clinical indication for treatment w/ a statin Rx & did not receive a statin medication prior to enrollment in the study.
Pre-assignment details
Patients with cardiomyopathy on the basis of valvular heart disease or who had a myocardial infarction within six months prior to study enrollment were excluded from the study.
Participants by arm
| Arm | Count |
|---|---|
| Ischemic Cardiomyopathy Patients with Ischemic Cardiomyopathy receiving Lipitor. | 1 |
| NonIschemic Cardiomyopathy NonIschemic Cardiomyopathy receiving Lipitor treatment | 4 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 2 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | NonIschemic Cardiomyopathy | Ischemic Cardiomyopathy | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 1 Participants | 5 Participants |
| Age, Continuous | 53.66 years STANDARD_DEVIATION 9.71 | 51.33 years STANDARD_DEVIATION 15.29 | 52.11 years STANDARD_DEVIATION 17.37 |
| Region of Enrollment United States | 4 participants | 1 participants | 5 participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 3 Participants | 1 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 1 | 0 / 4 |
| serious Total, serious adverse events | 0 / 1 | 0 / 4 |
Outcome results
Primary
Change in Endothelial Progenitor Cells
Change in Endothelial Progenitor Cells (EPC) was assessed by extracting white blood cells from blood samples and labeling the white blood cells using the ALDEFLOUR system. Facscan analysis was then performed first isolating lymphocytic and monocytic cell lines, which contain the EPC populations, using forward versus side scatter plots. These cells were then scanned for fluorescence in the ALDEFLUOR frequency range allowing enumeration of progenitor cell lines. The measures of fluorescent cells was compared to numbers of unstained cells having the same back scatter range to correct for any background fluorescence.
Time frame: Baseline - 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ischemic Cardiomyopathy | Change in Endothelial Progenitor Cells | -10.01 Percentage of EPCs | Standard Deviation 0 |
| NonIschemic Cardiomyopathy | Change in Endothelial Progenitor Cells | 5.19 Percentage of EPCs | Standard Deviation 0.517 |
Primary
Percentage Aldofluor Positive Cells
The primary outcome measure is the percentage of cells of total analyzed that are positive for the Aldofluor assay. This commercially available assay tests cells for the enzyme aldehyde dehydrogenase that is expressed in stem cells and other early life cycle undifferentiated cells. It thus provides a measure of circulating primordial cells or cells that may serve as progenitors of destination mature cells. The percentages are designed from Facscan analysis of prepared blood cells and are quantified by quadrants defined by specific fluorescent bands and cell size distribution. The quantification of cells thus defined in the four quadrants is automatically determined by software resident in the facscan analysis system.
Time frame: Baseline - 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ischemic Cardiomyopathy | Percentage Aldofluor Positive Cells | 6.37 Percentage Aldefluor positive cells | Standard Deviation 0 |
| NonIschemic Cardiomyopathy | Percentage Aldofluor Positive Cells | 5.7 Percentage Aldefluor positive cells | Standard Deviation 0.5 |
Comparison: The data were analyzed using analysis of variance for repeated measures with two groups. The repeated measure was the proportion of circulating blood cells that were positive for aldehyde dehydrogenase using the commercially available Aldofluor assay. The two groups were those with ischemic and non-ischemic cardiomyopathy. This analysis permitted both intergroup and intragroup analysis of the change in aldehyde dehydrogenase positive cells.p-value: <0.05ANOVA