Cardiovascular Disease, Chronic Kidney Disease
Conditions
Keywords
cardiovascular disease, angiotensin converting enzyme inhibitors, chronic kidney disease, cardiovascular disease in elderly patients with CKD
Brief summary
The goal of this proposal is to investigate the potential for ACE-inhibitors (ACE-I)(drugs primarily used to treat hypertension or congestive heart failure) to prevent or delay cardiovascular disease (CVD) in older adults with chronic kidney disease (CKD) by examining their impact on aortic stiffness in people with stage 3 CKD in a randomized, controlled study.
Detailed description
This study will be the first to examine whether aortic stiffness is increased in elderly patients with CKD compared to their age-matched healthy controls and further examine whether ACE-I may delay the progression of aortic stiffness in elderly CKD patients. If ACE-I therapy appears beneficial in preventing or delaying arterial stiffening in elderly patients with CKD, this work has important implications for improving the overall health of this population.
Interventions
Active comparator in chronic kidney disease and age matched control will take 1x40mg per day Placebo comparator in chronic kidney disease and age matched control will take 1 placebo pill per day
DRUGlisinopril
1 x 40 mg per day
Sponsors
University of Wisconsin, Madison
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
60 Years to 89 Years
Healthy volunteers
Yes
Inclusion criteria
* Age \> 60 years * BP 120/80 or higher \*(bps will be checked weekly first 4 weeks to ensure \< 130/80 - IF bp remains \> 130/80 we will administer other bp meds per JNC VII guidelines) * CKD stage 3 (GFR 30 - 59 ml/min) for CKD group; no CKD for control group
Exclusion criteria
* Known significant CVD (history of Myocardial infarction (MI), recurrent stroke, or New York Heart Association (NYHA) class III or greater). * Serum potassium \> 5.2 meq/L * Known allergy or hypersensitivity to ACE inhibitor or ARB * Female of childbearing age not practicing contraception * Current treatment with an Angiotensin Converting Enzyme Inhibitors (ACE-I) or Angiotensin-Receptor Blockers (ARB) (Note: can participate if on ACE-I after 6 week washout period) * History of ACE-I induced angioedema * History of angioedema, hereditary or idiopathic * Persons lacking consent capacity * 500 mg/dL proteinuria on 2 consecutive spot urine protein/creat ratios
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Aortic Pulse Wave Velocity (PWV) | up to 12 months | PWV will be measured in patients over age 60 with stage 3 CKD and age matched controls without CKD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Vascular Stiffness As Measured by PWV | baseline and 12 months | Comparison between Participants with Stage 3 Chronic Kidney Disease (CKD) and age matched Controls without CKD. The numbers reported are the mean of all the participants in the group at two points in time - the baseline and at 12 months for CFPWV, CBPWV, and CRPWV. Carotid-Femoral Pulse Wave Velocity (CFPWV) Carotid-Brachial Pulse Wave Velocity (CBPWV) Carotid-Radial Pulse Wave Velocity (CRPWV) |
| Change in Blood Pressure From Baseline to 12 Months | up to 12 months | Change in Blood Pressure will be used to measure the effect of ACE-inhibitors on the clinical markers of Cardiovascular Disease in participants with stage 3 CKD. |
Countries
United States
Participant flow
Recruitment details
Recruitment occurred between January 2009 and May 2009. Patients were told about this study from the nephrologist or study coordinator around the time of their usual kidney clinic visit. Controls were enrolled through a group on campus who connects volunteers with research studies.
Pre-assignment details
There is limited data for this study, the PI is now in private practice and some raw data no longer exists to answer this outcome. We have done our due diligence to populate this record with data that remains.
Participants by arm
| Arm | Count |
|---|---|
| Chronic Kidney Disease-ACE-I ace inhibitor
lisinopril: 1 x 40 mg per day | 8 |
| Chronic Kidney Disease angiotensin converting enzyme inhibitor: Active comparator in chronic kidney disease and age matched control will take 1x40mg per day Placebo comparator in chronic kidney disease and age matched control will take 1 placebo pill per day | 4 |
| Age Matched Control-ACE-I ace-inhibitor
lisinopril: 1 x 40 mg per day | 17 |
| Age Matched Control Placebo
angiotensin converting enzyme inhibitor: Active comparator in chronic kidney disease and age matched control will take 1x40mg per day Placebo comparator in chronic kidney disease and age matched control will take 1 placebo pill per day | 14 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Other | 1 | 2 | 8 | 3 |
| Overall Study | Physician Decision | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Chronic Kidney Disease-ACE-I | Chronic Kidney Disease | Age Matched Control-ACE-I | Age Matched Control | Total |
|---|---|---|---|---|---|
| Age, Continuous | 65 years | 87 years | 63.4 years | 67.3 years | 68 years |
| Race and Ethnicity Not Collected | — | — | — | — | 0 Participants |
| Region of Enrollment United States | 8 participants | 4 participants | 17 participants | 14 participants | 43 participants |
| Serum Creatinine | 1.3 mg/dL STANDARD_DEVIATION 0.3 | 0.8 mg/dL STANDARD_DEVIATION 1.8 | NA mg/dL | NA mg/dL | NA mg/dL |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 13 Participants | 11 Participants | 28 Participants |
| Sex: Female, Male Male | 5 Participants | 3 Participants | 4 Participants | 3 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 4 | 0 / 17 | 0 / 14 |
| other Total, other adverse events | 2 / 8 | 1 / 4 | 3 / 17 | 1 / 14 |
| serious Total, serious adverse events | 0 / 8 | 0 / 4 | 0 / 17 | 0 / 14 |
Outcome results
Primary
Aortic Pulse Wave Velocity (PWV)
PWV will be measured in patients over age 60 with stage 3 CKD and age matched controls without CKD.
Time frame: up to 12 months
Population: Comparison of the baseline pulse wave velocity measures between the two groups (CKD vs no CKD) prior to intervention with ACE inhibitor. Data analyzed is from 32 participants due to drop out either from study self withdrawal (3) or ineligibility (1 = BP too low to start medication) and 7 without adequate testing data available for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chronic Kidney Disease | Aortic Pulse Wave Velocity (PWV) | Carotid-Femoral Pulse Wave Velocity | 9.90 m/s | Standard Deviation 1.12 |
| Chronic Kidney Disease | Aortic Pulse Wave Velocity (PWV) | Carotid-Brachial Pulse Wave Velocity | 7.62 m/s | Standard Deviation 1.76 |
| Chronic Kidney Disease | Aortic Pulse Wave Velocity (PWV) | Carotid-Radial Pulse Wave Velocity | 9.03 m/s | Standard Deviation 2.12 |
| Age Matched Control | Aortic Pulse Wave Velocity (PWV) | Carotid-Femoral Pulse Wave Velocity | 9.96 m/s | Standard Deviation 2.52 |
| Age Matched Control | Aortic Pulse Wave Velocity (PWV) | Carotid-Brachial Pulse Wave Velocity | 8.57 m/s | Standard Deviation 1.46 |
| Age Matched Control | Aortic Pulse Wave Velocity (PWV) | Carotid-Radial Pulse Wave Velocity | 8.38 m/s | Standard Deviation 1.76 |
Comparison: p-value for CBPWV between CKD and Control groupsp-value: 0.685t-test, 2 sided
Comparison: p-value for CRPWV between CKD and Control groupsp-value: 0.739t-test, 2 sided
Comparison: p-value for CFPWV between CKD and Control groupsp-value: 0.471t-test, 2 sided
Secondary
Change in Blood Pressure From Baseline to 12 Months
Change in Blood Pressure will be used to measure the effect of ACE-inhibitors on the clinical markers of Cardiovascular Disease in participants with stage 3 CKD.
Time frame: up to 12 months
Population: There is limited data for this study, the PI is now in private practice and the raw data no longer exists to answer this outcome. We have done our due diligence to populate this record with data that remains.
Secondary
Mean Vascular Stiffness As Measured by PWV
Comparison between Participants with Stage 3 Chronic Kidney Disease (CKD) and age matched Controls without CKD. The numbers reported are the mean of all the participants in the group at two points in time - the baseline and at 12 months for CFPWV, CBPWV, and CRPWV. Carotid-Femoral Pulse Wave Velocity (CFPWV) Carotid-Brachial Pulse Wave Velocity (CBPWV) Carotid-Radial Pulse Wave Velocity (CRPWV)
Time frame: baseline and 12 months
Population: Participants in each arm that had measurements for both baseline and 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chronic Kidney Disease | Mean Vascular Stiffness As Measured by PWV | CFPWV Baseline | 10.20 m/s | Standard Deviation 0.99 |
| Chronic Kidney Disease | Mean Vascular Stiffness As Measured by PWV | CBPWV Baseline | 7.87 m/s | Standard Deviation 1.7 |
| Chronic Kidney Disease | Mean Vascular Stiffness As Measured by PWV | CRPWV Baseline | 9.03 m/s | Standard Deviation 0.93 |
| Chronic Kidney Disease | Mean Vascular Stiffness As Measured by PWV | CFPWV 12 months | 11.07 m/s | Standard Deviation 2.29 |
| Chronic Kidney Disease | Mean Vascular Stiffness As Measured by PWV | CBPWV 12 months | 8.40 m/s | Standard Deviation 2.5 |
| Chronic Kidney Disease | Mean Vascular Stiffness As Measured by PWV | CRPWV 12 months | 8.57 m/s | Standard Deviation 2.03 |
| Age Matched Control | Mean Vascular Stiffness As Measured by PWV | CRPWV 12 months | 8.66 m/s | Standard Deviation 2.87 |
| Age Matched Control | Mean Vascular Stiffness As Measured by PWV | CBPWV Baseline | 6.28 m/s | — |
| Age Matched Control | Mean Vascular Stiffness As Measured by PWV | CBPWV 12 months | 8.28 m/s | Standard Deviation 0.54 |
| Age Matched Control | Mean Vascular Stiffness As Measured by PWV | CRPWV Baseline | 4.80 m/s | — |
| Age Matched Control | Mean Vascular Stiffness As Measured by PWV | CFPWV Baseline | 7.95 m/s | — |
| Age Matched Control | Mean Vascular Stiffness As Measured by PWV | CFPWV 12 months | 10.66 m/s | Standard Deviation 2.78 |
| Age Matched Control-ACE-I | Mean Vascular Stiffness As Measured by PWV | CRPWV 12 months | 8.16 m/s | Standard Deviation 1.93 |
| Age Matched Control-ACE-I | Mean Vascular Stiffness As Measured by PWV | CBPWV 12 months | 8.65 m/s | Standard Deviation 1.87 |
| Age Matched Control-ACE-I | Mean Vascular Stiffness As Measured by PWV | CFPWV 12 months | 8.33 m/s | Standard Deviation 1.06 |
| Age Matched Control-ACE-I | Mean Vascular Stiffness As Measured by PWV | CBPWV Baseline | 9.14 m/s | Standard Deviation 0.82 |
| Age Matched Control-ACE-I | Mean Vascular Stiffness As Measured by PWV | CRPWV Baseline | 9.75 m/s | Standard Deviation 0.95 |
| Age Matched Control-ACE-I | Mean Vascular Stiffness As Measured by PWV | CFPWV Baseline | 9.96 m/s | Standard Deviation 2.52 |
| Age Matched Control | Mean Vascular Stiffness As Measured by PWV | CRPWV Baseline | 8.95 m/s | Standard Deviation 1.69 |
| Age Matched Control | Mean Vascular Stiffness As Measured by PWV | CRPWV 12 months | 9.43 m/s | Standard Deviation 1.71 |
| Age Matched Control | Mean Vascular Stiffness As Measured by PWV | CFPWV Baseline | 9.55 m/s | Standard Deviation 2.64 |
| Age Matched Control | Mean Vascular Stiffness As Measured by PWV | CBPWV Baseline | 8.17 m/s | Standard Deviation 1.61 |
| Age Matched Control | Mean Vascular Stiffness As Measured by PWV | CFPWV 12 months | 9.79 m/s | Standard Deviation 1.97 |
| Age Matched Control | Mean Vascular Stiffness As Measured by PWV | CBPWV 12 months | 8.06 m/s | Standard Deviation 2.02 |
Comparison: This p-value compares the baseline CBPWV measures for the CKD vs Controls groupp-value: 0.685t-test, 2 sided
Comparison: This p-value compares the 12 month CBPWV measures for the CKD vs Controls groupp-value: 0.869t-test, 2 sided
Comparison: This p-value compares the baseline CRPWV measures for the CKD vs Controls groupp-value: 0.709t-test, 2 sided
Comparison: This p-value compares the 12 month CBPWV measures for the CKD vs Controls groupp-value: 0.34t-test, 2 sided
Comparison: This p-value compares the baseline CFPWV measures for the CKD vs Controls groupp-value: 0.73t-test, 2 sided
Comparison: This p-value compares the 12 month CFPWV measures for the CKD vs Controls groupp-value: 0.204t-test, 2 sided
Comparison: This compares the 12 month CBPWV measure of ACE-I CKD and Control groupsp-value: 0.963t-test, 2 sided
Comparison: This compares the 12 month CRPWV measure of ACE-I CKD and Control groupsp-value: 0.991t-test, 2 sided
Comparison: This compares the 12 month CFPWV measure of ACE-I CKD and Control groupsp-value: 0.176t-test, 2 sided
Comparison: This compares the baseline and 12 month CBPWV measure of the ACE-I CKDp-value: 0.402t-test, 2 sided
Comparison: This compares the baseline and 12 month CRPWV measure of the ACE-I CKDp-value: 0.586t-test, 2 sided
Comparison: This compares the baseline and 12 month CFPWV measure of the ACE-I CKDp-value: 0.455t-test, 2 sided
Comparison: This compares the baseline and 12 month CBPWV measure of the ACE-I Control Groupp-value: 0.418t-test, 2 sided
Comparison: This compares the baseline and 12 month CRPWV measure of the ACE-I Control Groupp-value: 0.091t-test, 2 sided
Comparison: This compares the baseline and 12 month CFPWV measure of the ACE-I Control Groupp-value: 0.034t-test, 2 sided
Comparison: This compares the 12 month CBPWV measure of the CKD and Control groupsp-value: 0.921t-test, 2 sided
Comparison: This compares the 12 month CRPWV measure of the CKD and Control groupsp-value: 0.887t-test, 2 sided
Comparison: This compares the 12 month CFPWV measure of the CKD and Control groupsp-value: 0.759t-test, 2 sided
Comparison: This compares the baseline and 12 month CBPWV measure of the Control groupsp-value: 0.851t-test, 2 sided
Comparison: This compares the baseline and 12 month CRPWV measure of the Control groupsp-value: 0.733t-test, 2 sided
Comparison: This compares the baseline and 12 month CFPWV measure of the Control groupsp-value: 0.902t-test, 2 sided
Comparison: This compares the 12 month CBPWV measure between the CKD ACE-I and CKD Control groups.p-value: 0.414t-test, 2 sided
Comparison: This compares the 12 month CRPWV measure between the CKD ACE-I and CKD Control groups.p-value: 0.942t-test, 2 sided
Comparison: This compares the 12 month CFPWV measure between the CKD ACE-I and CKD Control groups.p-value: 0.99t-test, 2 sided
Comparison: This compares the 12 month CBPWV measure between the ACE-I Control and CKD Control groups.p-value: 0.273t-test, 2 sided
Comparison: This compares the 12 month CRPWV measure between the ACE-I Control and CKD Control groups.p-value: 0.516t-test, 2 sided
Comparison: This compares the 12 month CFPWV measure between the ACE-I Control and CKD Control groups.p-value: 0.102t-test, 2 sided