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

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.

Study Overview

• Status: Terminated
• Conditions: Endothelial Dysfunction
• Intervention / Treatment: Drug: Aliskiren; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Aliskiren; 150 mg Aliskiren once daily for a period of 4 months.	Drug: Aliskiren; 150 mg Aliskiren once daily for a period of 4 months; Other Names: Rasilez; Tekturna
Placebo Comparator: Placebo; 1 pill per day by mouth for 4 months.	Drug: Placebo; 1 pill per day by mouth for 4 months

What is the study measuring?

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	Time Frame
Systolic Blood Pressure	Baseline, 4 Months
Diastolic Blood Pressure	Baseline, 4 Months

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Novartis; National Institute on Aging (NIA)

Publications and helpful links

General Publications

• Flammer AJ, Gossl M, Li J, Reriani M, Shonyo S, Loeffler D, Herrmann J, Lerman LO, Lerman A. Renin inhibition with aliskiren lowers circulating endothelial progenitor cells in patients with early atherosclerosis. J Hypertens. 2013 Mar;31(3):632-5. doi: 10.1097/HJH.0b013e32835c6d2d. No abstract available.

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: February 8, 2010
• First Submitted That Met QC Criteria: February 10, 2010
• First Posted (Estimate): February 11, 2010

Study Record Updates

• Last Update Posted (Estimate): February 13, 2013
• Last Update Submitted That Met QC Criteria: January 9, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: Endothelial Function; Endothelial Dysfunction; Tekturna; Endothelial Peripheral Arterial Tomography (EndoPAT); Progenitor Cells; renin inhibition; endothelial progenitor cells; early atherosclerosis
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis
• Other Study ID Numbers: 09-007617; R01AG031750 (U.S. NIH Grant/Contract); R01HL092954 (U.S. NIH Grant/Contract)