The Effect of Tekturna on Endothelial Function and Endothelial Progenitor Cells in Patients With Early Atherosclerosis
Condition: Endothelial Dysfunction
MeSH terms: Atherosclerosis
Intervention: Aliskiren; Placebo
Intervention description: 150 mg Aliskiren once daily for a period of 4 months; 1 pill per day by mouth for 4 months
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Endothelial Dysfunction; Endothelial Function; Tekturna; Endothelial Peripheral Arterial Tomography (EndoPAT); Progenitor Cells; renin inhibition; endothelial progenitor cells; early atherosclerosis

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age > 18 years old

          2. 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

          3. Demonstrated endothelial dysfunction (reactive hyperemia - EndoPAT score < 2.0) at
             time of screening

        Exclusion Criteria:

          1. Serum potassium > 5.0 mmol/L documented at any time prior to the study

          2. 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

          3. 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

          4. Congestive heart failure New York Heart Association (NYHA) class III and IV

          5. 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

          6. Unstable serum creatinine

          7. Second (II) or third (III) degree heart block without a pacemaker

          8. Concurrent potentially life threatening arrhythmia or other uncontrolled arrhythmia

          9. Clinically significant valvular heart disease

         10. Known renal artery stenosis

         11. 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

         12. History of malignancy other than basal cell skin cancer within the past five years

         13. Any concurrent life threatening condition with a life expectancy less than 2 years

         14. History or evidence of drug or alcohol abuse within the last 12 months

         15. 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

         16. 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

         17. History of noncompliance to medical regimens or unwillingness to comply with the study
             protocol

         18. Use of other investigational drugs at the time of enrollment, or within 30 days or 5
             half-lives of enrollment, whichever is longer

         19. Any condition that in the opinion of the investigator would jeopardize the evaluation
             of efficacy or safety

         20. Persons directly involved in the execution of this protocol

         21. Pregnant or nursing (lactating) women

         22. 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