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

Endothelial Dysfunction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01067326
• Other study ID #: 09-007617
• Secondary ID: R01AG031750R01HL
• Status: Terminated
• Phase: Phase 3
• First received: February 8, 2010
• Last updated: January 9, 2013
• Start date: February 2010
• Est. completion date: December 2011

Study information

• Verified date: January 2013
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 22
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atherosclerosis
• Endothelial Dysfunction

Intervention

Drug:
• Aliskiren
150 mg Aliskiren once daily for a period of 4 months
• Placebo
1 pill per day by mouth for 4 months

Locations

Country	Name	City	State
United States	Mayo Clinic in Rochester	Rochester	Minnesota

Sponsors (4)

Lead Sponsor	Collaborator
Mayo Clinic	National Heart, Lung, and Blood Institute (NHLBI), National Institute on Aging (NIA), Novartis

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	Systolic Blood Pressure		Baseline, 4 Months	No
Secondary	Diastolic Blood Pressure		Baseline, 4 Months	No