Effect of Nebivolol on Oxidative Stress and Endothelial Progenitor Cells

NCT ID: NCT01041287

Last Updated: 2014-12-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 96 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-31
• Study Completion Date: 2013-12-31

Brief Summary

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.

Conditions

Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Nebivolol/ Metoprolol

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.

Group Type: ACTIVE_COMPARATOR

Nebivolol

Intervention Type: DRUG

Nebivolol 5 mg PO qday for 2 weeks, titrated up to Nebivolol 10 mg PO qday if BP is \>125/80 for the 2 more weeks, and then titrated up to Nebivolol 20 mg PO qday if BP is \>125/80 for the remaining 8 weeks

Metoprolol succinate

Intervention Type: DRUG

Metoprolol 50 mg PO qday for 2 weeks, titrated up to Metoprolol 100 mg PO qday if BP is \>125/80 for the 2 more weeks, and then titrated up to Metoprolol 200 mg PO qday if BP is \>125/80 for the remaining 8 weeks

Metoprolol/Nebivolol

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.

Group Type: ACTIVE_COMPARATOR

Nebivolol

Intervention Type: DRUG

Nebivolol 5 mg PO qday for 2 weeks, titrated up to Nebivolol 10 mg PO qday if BP is \>125/80 for the 2 more weeks, and then titrated up to Nebivolol 20 mg PO qday if BP is \>125/80 for the remaining 8 weeks

Metoprolol succinate

Intervention Type: DRUG

Metoprolol 50 mg PO qday for 2 weeks, titrated up to Metoprolol 100 mg PO qday if BP is \>125/80 for the 2 more weeks, and then titrated up to Metoprolol 200 mg PO qday if BP is \>125/80 for the remaining 8 weeks

Interventions

Nebivolol

Nebivolol 5 mg PO qday for 2 weeks, titrated up to Nebivolol 10 mg PO qday if BP is \>125/80 for the 2 more weeks, and then titrated up to Nebivolol 20 mg PO qday if BP is \>125/80 for the remaining 8 weeks

Intervention Type: DRUG

Metoprolol succinate

Metoprolol 50 mg PO qday for 2 weeks, titrated up to Metoprolol 100 mg PO qday if BP is \>125/80 for the 2 more weeks, and then titrated up to Metoprolol 200 mg PO qday if BP is \>125/80 for the remaining 8 weeks

Intervention Type: DRUG

Other Intervention Names

Bystolic; Toprol XL

Eligibility Criteria

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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Forest Laboratories

INDUSTRY

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Arshed A. Quyyumi

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Arshed Quyyumi, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Emory University

Atlanta, Georgia, United States

Countries

United States

References

Hayek SS, Poole JC, Neuman R, Morris AA, Khayata M, Kavtaradze N, Topel ML, Binongo JG, Li Q, Jones DP, Waller EK, Quyyumi AA. Differential effects of nebivolol and metoprolol on arterial stiffness, circulating progenitor cells, and oxidative stress. J Am Soc Hypertens. 2015 Mar;9(3):206-13. doi: 10.1016/j.jash.2014.12.013. Epub 2014 Dec 31.

Reference Type: DERIVED

PMID: 25681236 (View on PubMed)

Other Identifiers

BYD-MD-20

Identifier Type: OTHER

Identifier Source: secondary_id

IRB00013262

Identifier Type: -

Identifier Source: org_study_id