The Effect of Nebivolol on Endothelial Dysfunction in African Americans With Hypertension

NCT ID: NCT01049009

Last Updated: 2017-04-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 91 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-31
• Study Completion Date: 2012-06-30

Brief Summary

High blood pressure (hypertension) is called the "silent killer" because many people do not know they have it, and do not know when it is well controlled. Unfortunately, over time uncontrolled hypertension can cause irreversible organ damage that can lead to heart attack, stroke, heart failure, and kidney failure. If a person cannot control their blood pressure with diet and exercise, doctors often prescribe medications to help control the blood pressure. Nebivolol is a medication that has been recently approved by the FDA for the treatment of hypertension. Our study will investigate whether treatment with nebivolol, as compared to another medication called metoprolol, in African Americans with hypertension will be more effective in protecting blood vessels against the harmful effects of high blood pressure.

Over time high blood pressure causes hardening of the arteries (atherosclerosis) which leads to narrowing of the blood vessels and reduces blood flow to our organs. Arteries also relax and contract naturally, which further changes the blood supply. When arteries are narrowed, exercise can bring on a condition in which the blood supply is inadequate, and this might result in the sensation of pain.

Cells lining our blood vessels produce a variety of substances that normally cause arteries to relax. Two of these substances are called nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). We are trying to determine the nature of these substances in African Americans with high blood pressure and how it is affected by nebivolol and metoprolol. One way to determine this is to inject drugs such as L-NMMA (N(G)-monomethyl-L-arginine) or TEA (tetraethylammonium chloride), which block the production of NO and EDHF respectively, and then study what happens to the blood flow at rest and during exercise. It is our thought that nebivolol, in comparison to metoprolol, will increase the substances that naturally cause arteries to relax and improve blood supply.

Conditions

High Blood Pressure

Study Design

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

Study Groups

Nebivolol followed by Metoprolol XL

Subjects are randomized to Nebivolol 5mg and titrate to Nebivolol 10mg two weeks after drug initiation. Ten weeks after titration subjects will cross over to Metoprolol XL 50mg and titrate to Metoprolol XL 100mg two weeks after cross over.

Group Type: ACTIVE_COMPARATOR

Nebivolol

Intervention Type: DRUG

Subjects will be randomized to either nebivolol or metoprolol xl, and remain on the study drug for 10 weeks. They will then "cross over" to take 10 weeks of the comparator drug.

Metoprolol XL

Intervention Type: DRUG

Subjects will be randomized to either nebivolol or metoprolol xl, and remain on the study drug for 10 weeks. They will then "cross over" to take 10 weeks of the comparator drug.

Metoprolol XL followed by Nebivolol

Subjects are randomized to Metoprolol XL 50mg and titrate to Metoprolol XL 100mg two weeks after drug initiation. Ten weeks after titration subjects will cross over to Nebivolol 5mg and titrate to Nebivolol 10mg two weeks after cross over.

Group Type: ACTIVE_COMPARATOR

Nebivolol

Intervention Type: DRUG

Subjects will be randomized to either nebivolol or metoprolol xl, and remain on the study drug for 10 weeks. They will then "cross over" to take 10 weeks of the comparator drug.

Metoprolol XL

Intervention Type: DRUG

Subjects will be randomized to either nebivolol or metoprolol xl, and remain on the study drug for 10 weeks. They will then "cross over" to take 10 weeks of the comparator drug.

Interventions

Nebivolol

Subjects will be randomized to either nebivolol or metoprolol xl, and remain on the study drug for 10 weeks. They will then "cross over" to take 10 weeks of the comparator drug.

Intervention Type: DRUG

Metoprolol XL

Subjects will be randomized to either nebivolol or metoprolol xl, and remain on the study drug for 10 weeks. They will then "cross over" to take 10 weeks of the comparator drug.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male or post-menopausal females aged 18-80 years.
• Subjects self-identified as black or African-American.
• Diagnosis of hypertension.
• Patients on current anti-hypertensive therapy that does not include beta blockade should have BP >135/85.
• Patients on anti-hypertensive therapy including beta blockers will have their beta blockers discontinued gradually over 2 weeks before enrolment.
• Concomitant therapy: Patients will be allowed to be on concomitant therapy with aspirin, statins, thiazide diuretics, calcium antagonists (for treatment of hypertension), clonidine, or vasodilators. 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

• Initiation or change in dose of statin or other anti-hypertensive therapy within 2 months before the study
• Inability to return to Emory for follow-up testing
• Age < 21 or >80 years
• Premenopausal females with potential for pregnancy
• Acute infection in previous 2 weeks
• On angiotensin antagonists (ACE inhibitors or ARBs)
• 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

• 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

Locations

Emory University

Atlanta, Georgia, United States

Countries

United States

References

Neuman RB, Hayek SS, Poole JC, Rahman A, Menon V, Kavtaradze N, Polhemus D, Veledar E, Lefer DJ, Quyyumi AA. Nitric Oxide Contributes to Vasomotor Tone in Hypertensive African Americans Treated With Nebivolol and Metoprolol. J Clin Hypertens (Greenwich). 2016 Mar;18(3):223-31. doi: 10.1111/jch.12649. Epub 2015 Aug 19.

Reference Type: RESULT

PMID: 26285691 (View on PubMed)

Study Documents

Document Type: Publication

View Document

Other Identifiers

IRB00017946

Identifier Type: -

Identifier Source: org_study_id