The Effect of Tekturna on Endothelial Function and Endothelial Progenitor Cells in Patients With Early Atherosclerosis

Study Overview
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Brief Summary
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We will study the hypothesis that long-term Tekturna treatment will improve endothelial function and the production and function of endothelial progenitor cells (EPCs) in patients with early atherosclerosis. Specifically, long-term Tekturna treatment will increase the Reactive Hyperemia Peripheral Arterial Tonometry indexes and increase the numbers and the function of circulating endothelial progenitor cells, compared to placebo, in association with a reduction in inflammation and oxidative stress.

Detailed Description
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Aliskiren is a direct renin-inhibitor and may have beneficial effects on the vascular endothelium, similar to other antihypertensive therapies targeting the renin-angiotensin-aldosterone system (RAAS). The current study was designed to test the hypothesis that aliskiren improves endothelial function and increases the number of endothelial progenitor cells (EPCs) in normotensive patients with early atherosclerosis.

Official Title
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The Effect of Tekturna on Endothelial Function and Endothelial Progenitor Cells in Patients With Early Atherosclerosis

Conditions
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Endothelial Dysfunction

Intervention / Treatment
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* Drug: Aliskiren
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years old More than two of the following cardiovascular risk factors (determined by prescreen phone call): family history of cardiovascular disease, physical inactivity/sedentary lifestyle, obesity or overweight, family history of diabetes mellitus or hypertension, total cholesterol > 200 mg/dL, LDL > 130 mg/dL, HDL < 50 mg/dL, smoking, stress, or Triglycerides > 150 mg/dL Demonstrated endothelial dysfunction (reactive hyperemia - EndoPAT score < 2.0) at time of screening Exclusion Criteria: Serum potassium > 5.0 mmol/L documented at any time prior to the study History of any cardiovascular event (stroke, transient ischemic attack (TIA), myocardial infarction (MI), unstable angina, coronary artery bypass grafting (CABG), percutaneous coronary intervention, hospitalization due to heart failure) during the 3 months prior to the study Hypertension or hypotension (at Randomization): any patient with Mean Seated Systolic Blood Pressure (msSBP) ≥ 170 mmHg, msSBP < 100 mmHg or Mean Seated Diastolic Blood Pressure (msDBP) ≥ 110 mmHg Congestive heart failure New York Heart Association (NYHA) class III and IV Concomitant treatment with two (2) or more renin-angiotensin-aldosterone system blocking agents, e.g. Angiotensin Converting Enzyme Inhibitor (ACEI), Angiotensin II receptor blockers (ARB) or aldosterone-antagonist Unstable serum creatinine Second (II) or third (III) degree heart block without a pacemaker Concurrent potentially life threatening arrhythmia or other uncontrolled arrhythmia Clinically significant valvular heart disease Known renal artery stenosis Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of the study drugs including, but not limited to, any of the following: History of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection Any history of pancreatic injury, pancreatitis or evidence of impaired pancreatic function/injury as indicated by abnormal lipase or amylase Evidence of hepatic disease as determined by a history of hepatic encephalopathy, a history of cirrhosis, esophageal varices, or a history of portocaval shunt History of malignancy other than basal cell skin cancer within the past five years Any concurrent life threatening condition with a life expectancy less than 2 years History or evidence of drug or alcohol abuse within the last 12 months Any surgical or medical condition, which in the opinion of the investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study History of hypersensitivity to any of the study drugs or to medications belonging to the same therapeutic class as the study drugs as well as known or suspected contraindications to the study drugs History of noncompliance to medical regimens or unwillingness to comply with the study protocol Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer Any condition that in the opinion of the investigator would jeopardize the evaluation of efficacy or safety Persons directly involved in the execution of this protocol Pregnant or nursing (lactating) women Women of Child-Bearing Potential (WOCBP) unless postmenopausal for at least one year, surgically sterile or using effective methods of contraception as defined by local Health Authorities

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Aliskiren<br>150 mg Aliskiren once daily for a period of 4 months. | Drug: Aliskiren<br>* 150 mg Aliskiren once daily for a period of 4 months<br>* Other names: Rasilez;|
| Placebo Comparator: Placebo<br>1 pill per day by mouth for 4 months. | Drug: Placebo<br>* 1 pill per day by mouth for 4 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endothelial Progenitor Cells (EPC) | Peripheral blood mononuclear cells were stained for EPC markers (cell-surface antigens CD34/CD133/KDR) and counted by flow-cytometry. | Baseline, 4 Months | 
| Reactive Hyperemia Index (RHI) | RHI was measured by the noninvasive endothelial peripheral arterial tomography (EndoPat) test. EndoPAT results are reported as the Endoscore (range 0-3); a score of 1.67 and lower indicates the need for immediate medical attention; a score between 1.68 and 2 indicates a need to reduce risk factors; a score above 2.1 indicates a healthy heart. | Baseline, 4 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systolic Blood Pressure |  | Baseline, 4 Months | 
| Diastolic Blood Pressure |  | Baseline, 4 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Endothelial Dysfunction, Endothelial Function, Tekturna, Endothelial Peripheral Arterial Tomography (EndoPAT), Progenitor Cells, renin inhibition, endothelial progenitor cells, early atherosclerosis