Effect of Nebivolol on Oxidative Stress and Endothelial Progenitor Cells

• ClinicalTrials.gov Identifier: NCT01041287
• Recruitment Status: Completed
• First Posted: December 31, 2009
• Results First Posted: December 19, 2014
• Last Update Posted: December 19, 2014
• Sponsor: Emory University
• Collaborator: Forest Laboratories
• Information provided by (Responsible Party): Arshed A. Quyyumi, Emory University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Hypertension	Drug: Nebivolol; Drug: Metoprolol succinate	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 96 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Effect of Nebivolol on Oxidative Stress and Endothelial Progenitor Cells in Subjects With Hypertension
• Study Start Date: December 2009
• Actual Primary Completion Date: December 2013
• Actual Study Completion Date: December 2013

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 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.	Drug: 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; Other Name: Bystolic; 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; Other Name: Toprol XL
Active Comparator: 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.	Drug: 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; Other Name: Bystolic; 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; Other Name: Toprol XL

Outcome Measures

Primary Outcome Measures :

1. Pulse Wave Velocity (Measure of Arterial Stiffness) [ Time Frame: Baseline ]
   The pulse wave velocity (PWV) system measured the velocity of the blood pressure waveform between the carotid and femoral arteries using a single-lead electrocardiogram and tonometer to measure the pressure pulse waveform sequentially at the two peripheral artery sites. PWV is calculated as PWV=distance (d)/time (t) and the unit of measure is reported as meters per second (m/s).
2. Pulse Wave Velocity (Measure of Arterial Stiffness) [ Time Frame: 3 months ]
   The pulse wave velocity (PWV) system measured the velocity of the blood pressure waveform between the carotid and femoral arteries using a single-lead electrocardiogram and tonometer to measure the pressure pulse waveform sequentially at the two peripheral artery sites. PWV is calculated as PWV=distance (d)/time (t) and the unit of measure is reported as meters per second (m/s).
3. Pulse Wave Velocity (Measure of Arterial Stiffness) [ Time Frame: 6 months ]
   The pulse wave velocity (PWV) system measured the velocity of the blood pressure waveform between the carotid and femoral arteries using a single-lead electrocardiogram and tonometer to measure the pressure pulse waveform sequentially at the two peripheral artery sites. PWV is calculated as PWV=distance (d)/time (t) and the unit of measure is reported as meters per second (m/s).

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Georgia

Emory University

Atlanta, Georgia, United States, 30322

Sponsors and Collaborators

Emory University

Forest Laboratories

Investigators

• Principal Investigator: Arshed Quyyumi, MD; Emory University

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Arshed A. Quyyumi, Professor, Emory University
• ClinicalTrials.gov Identifier: NCT01041287
• Other Study ID Numbers: IRB00013262; BYD-MD-20 ( Other Identifier: Other )
• First Posted: December 31, 2009
• Results First Posted: December 19, 2014
• Last Update Posted: December 19, 2014
• Last Verified: December 2014

Additional relevant MeSH terms:

Hypertension; Vascular Diseases; Cardiovascular Diseases; Metoprolol; Nebivolol; Anti-Arrhythmia Agents; Antihypertensive Agents; Sympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Adrenergic beta-1 Receptor Antagonists; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Adrenergic beta-1 Receptor Agonists; Adrenergic beta-Agonists; Adrenergic Agonists