Effect of Nebivolol on Oxidative Stress and Endothelial Progenitor Cells

NCT01041287 | Completed Phase 4 Results

• 2 other identifiers: IRB00013262BYD-MD-20
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (3)

• Pulse Wave Velocity (Measure of Arterial Stiffness)

  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).

  Baseline

• Pulse Wave Velocity (Measure of Arterial Stiffness)

  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 months

• Pulse Wave Velocity (Measure of Arterial Stiffness)

  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).

  6 months

Study Arms (2)

Nebivolol/ Metoprolol

ACTIVE COMPARATOR

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; Drug: Metoprolol succinate

Metoprolol/Nebivolol

ACTIVE COMPARATOR

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; Drug: Metoprolol succinate

Interventions

Nebivolol 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

Also known as: Bystolic

Metoprolol/Nebivolol; Nebivolol/ Metoprolol

Metoprolol succinate 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

Also known as: Toprol XL

Metoprolol/Nebivolol; Nebivolol/ Metoprolol

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or post-menopausal females aged 21-80 years.
• Hypertensive patients (BP \>135/85) will be eligible to participate.
• Patients on current anti-hypertensive therapy that does not include beta blockade should have BP \>135/85.
• Patients on anti-hypertensive therapy including beta blockade will have their beta blockers discontinued gradually over 2 weeks before enrolment.
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Emory University: lead
• Forest Laboratories: collaborator

Study Sites (1)

Emory University

Atlanta, Georgia, 30322, United States

Location

Related Publications (1)

• 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.

  PMID: 25681236 DERIVED

MeSH Terms

Conditions

Hypertension

Interventions

Nebivolol; Metoprolol

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Phenoxypropanolamines; Propanolamines; Propanols

Results Point of Contact

• Title: Dr. Arshed Quyyumi
• Organization: Emory University

aquyyum@emory.edu

404-727-3655

Study Officials

• Arshed Quyyumi, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 29, 2009
• First Posted: December 31, 2009
• Study Start: December 1, 2009
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: December 19, 2014
• Results First Posted: December 19, 2014

Record last verified: 2014-12

Locations

US (1)