Effect of Nebivolol on Oxidative Stress and Endothelial Progenitor Cells

Emory University

Status and phase: Completed; Phase 4

Conditions: Hypertension

Treatments: Drug: Nebivolol; Drug: Metoprolol succinate

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01041287

BYD-MD-20 (Other Identifier)

IRB00013262

Details and patient eligibility

About

Hypertension, or high blood pressure, is a common disease that affects many Americans, and can lead to devastating consequences such as heart attack, stroke, and death if not treated. Nebivolol is a medication that has been recently approved by the FDA for the treatment of hypertension. Nebivolol has an unusual profile compared to other medications, in that its effects may be related to release of a substance called nitric oxide. Nitric oxide is released from the cells lining the blood vessels, and nebivolol may stimulate these cells to release more nitric oxide. Our study will investigate whether treatment with nebivolol, as compared to another medication called metoprolol, in hypertensive subjects will be more effective in protecting blood vessels against the harmful effects of high blood pressure. The mechanisms we will investigate include oxidative stress markers and circulating levels of endothelial progenitor cells.

Enrollment: 96 patients

Sex: All

Ages: 21 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Males or post-menopausal females aged 21-80 years.
2. Hypertensive patients (BP >135/85) will be eligible to participate.
3. Patients on current anti-hypertensive therapy that does not include beta blockade should have BP >135/85.
4. Patients on anti-hypertensive therapy including beta blockade will have their beta blockers discontinued gradually over 2 weeks before enrolment.
5. Concomitant therapy: Patients will be allowed to be on comcomitant therapy with aspirin, statins, thiazide diuretics, calcium antagonists (for treatment of hypertension), clonidine, vasodilators, or angiotensin antagonists. Patients will be on stable medical therapy for at least 2 months before recruitment. Patients with previous treatment with beta adrenergic blockers (metoprolol, propranolol, atenolol, and labetalol) will also be eligible to participate, but will be randomized to the study beta blocker.

Exclusion criteria

1. Age < 21 or >80 years
2. Initiation or change in dose of statin or anti-hypertensive therapy within 2 months before the study
3. Premenopausal females with potential for pregnancy
4. Acute infection in previous 2 weeks
5. History of substance abuse
6. Current neoplasm
7. Chronic renal failure [creatinine > 2.5 mg/dL] or liver failure (Liver enzymes >2X normal)
8. Acute coronary syndrome, Class IV heart failure, CVA, coronary intervention within 2 months
9. Known aortic stenosis, hypertrophic cardiomyopathy.
10. Inability to give informed consent
11. Inability to return to Emory for follow-up testing

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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96 participants in 2 patient groups

Nebivolol/ Metoprolol

Active Comparator group

Description:

Subjects were randomized to nebivolol for 3 months. They "crossed over" to take 3 months of metoprolol succinate. The initial 5 mg daily dose of nebivolol was titrated to 10 mg daily after 2 weeks if their BP remained \>125/80, and subsequently titrated to 20 mg daily after another 2 weeks if the BP remained \>125/80. Similarly, the initial 50 mg daily dose of metoprolol succinate was titrated to 100 mg daily after 2 weeks if BP remained \>125/80, and further increased to 200 mg after 2 weeks if BP remained \>125/80.

Treatment:

Drug: Metoprolol succinate

Drug: Nebivolol

Metoprolol/Nebivolol

Active Comparator group

Description:

Subjects were randomized to metoprolol succinate for 3 months. They "crossed over" to take 3 months of nebivolol. The initial 5 mg daily dose of nebivolol was titrated to 10 mg daily after 2 weeks if their BP remained \>125/80, and subsequently titrated to 20 mg daily after another 2 weeks if the BP remained \>125/80. Similarly, the initial 50 mg daily dose of metoprolol succinate was titrated to 100 mg daily after 2 weeks if BP remained \>125/80, and further increased to 200 mg after 2 weeks if BP remained \>125/80.

Treatment:

Drug: Metoprolol succinate

Drug: Nebivolol