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

High Blood Pressure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01049009
• Other study ID #: IRB00017946
• Status: Completed
• Phase: Phase 4
• First received: January 12, 2010
• Last updated: December 12, 2014
• Start date: December 2009
• Est. completion date: June 2012

Study information

• Verified date: December 2014
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 91
• Est. completion date: June 2012
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• High Blood Pressure
• Hypertension

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
Emory University	Forest Laboratories

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No