Effect of Nebivolol on Oxidative Stress and Endothelial Progenitor Cells

This study has been completed.
Sponsor:
Collaborator:
Forest Laboratories
Information provided by (Responsible Party):
Arshed A. Quyyumi, Emory University
ClinicalTrials.gov Identifier:
NCT01041287
First received: December 29, 2009
Last updated: December 12, 2014
Last verified: December 2014
  Purpose
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 Intervention Phase
Hypertension
Drug: Nebivolol
Drug: Metoprolol succinate
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Effect of Nebivolol on Oxidative Stress and Endothelial Progenitor Cells in Subjects With Hypertension

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • Pulse Wave Velocity (Measure of Arterial Stiffness) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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).

  • Pulse Wave Velocity (Measure of Arterial Stiffness) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    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).

  • Pulse Wave Velocity (Measure of Arterial Stiffness) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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).


Enrollment: 96
Study Start Date: December 2009
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   21 Years to 80 Years   (Adult, Senior)
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01041287

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):
Responsible Party: Arshed A. Quyyumi, Professor, Emory University
ClinicalTrials.gov Identifier: NCT01041287     History of Changes
Other Study ID Numbers: IRB00013262  BYD-MD-20 
Study First Received: December 29, 2009
Results First Received: December 12, 2014
Last Updated: December 12, 2014
Health Authority: United States: Institutional Review Board

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

ClinicalTrials.gov processed this record on August 25, 2016