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

NCT01049009 | Completed Phase 4 Results

• 1 other identifier: IRB00017946
• Study Type: interventional
• Target: 91
• Locations: 1 country
• Sites: 1

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

Keywords

Nitric Oxide; Adrenergic beta-Antagonists; Antihypertensive Agents; Vasodilator Agents; Anti-Arrhythmia Agents; Sympatholytics; Vascular Resistance; Neurotransmitter Agents; Cardiovascular Diseases; Metoprolol succinate; Therapeutic Uses; Metoprolol; Vascular Diseases; Nebivolol; Cardiovascular Agents; Endothelium-Dependent Relaxing Factors

Outcome Measures

Primary Outcomes (2)

• Endothelial Function Measured by Forearm Blood Flow (FBF) at 12 Weeks

  Forearm blood flow measured by venous occlusion plethysmography at rest, after administration of N(G)-monomethyl-L-arginine (L-NMMA) and tetraethylammonium chloride (TEA), after administration of L-NMMA, TEA, and acetylcholine, and after administration of L-NMMA, TEA, and exercise. Unit of Measure refers to volume of blood (mL) per 100 mL of forearm tissue per minute.

  12 weeks

• Endothelial Function Measured by Forearm Blood Flow (FBF) at 24 Weeks

  Forearm blood flow measured by venous occlusion plethysmography at rest, after administration of N(G)-monomethyl-L-arginine (L-NMMA) and tetraethylammonium chloride (TEA), after administration of L-NMMA, TEA, and acetylcholine, and after administration of L-NMMA, TEA, and exercise. Unit of Measure refers to volume of blood (mL) per 100 mL of forearm tissue per minute.

  24 weeks

Study Arms (2)

Nebivolol followed by Metoprolol XL

ACTIVE COMPARATOR

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.

Drug: Nebivolol; Drug: Metoprolol XL

Metoprolol XL followed by Nebivolol

ACTIVE COMPARATOR

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.

Drug: Nebivolol; Drug: Metoprolol XL

Interventions

Nebivolol 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; Nebivolol followed by Metoprolol XL

Metoprolol XL 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; Nebivolol followed by Metoprolol XL

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead
• Forest Laboratories: collaborator

Study Sites (1)

Emory University

Atlanta, Georgia, 30322, United States

Location

Related Publications (1)

• 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.

  PMID: 26285691 RESULT

MeSH Terms

Conditions

Hypertension; Cardiovascular Diseases; Vascular Diseases

Interventions

Nebivolol; Metoprolol

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 A. Quyyumi
• Organization: Emory University School of Medicine

aquyyum@emory.edu

404-727-3655

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

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: January 12, 2010
• First Posted: January 14, 2010
• Study Start: December 1, 2009
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: April 11, 2017
• Results First Posted: December 19, 2014

Record last verified: 2017-03

Locations

US (1)