Comparison of Nebivolol and Metoprolol With Exercise and Angiotensin II in Hypertensive Patients

The University of Texas System (UT)

Status and phase: Completed; Phase 4

Conditions: Hypertension

Treatments: Procedure: Rhythmic handgrip exercise; Procedure: Lower body negative pressure; Drug: Metoprolol succinate; Procedure: Microneurography; Procedure: Forearm blood flow; Drug: Nebivolol; Drug: Angiotensin II

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01502787

STU 062011-072

Details and patient eligibility

About

The purpose of this study is to determine if Nebivolol a) attenuates the angiotensin II (Ang II)-induced increase in oxidative stress, thereby attenuating Ang II-induced vasoconstriction; and b) attenuates sympathetic mediated vasoconstriction during exercise, thereby reducing functional skeletal muscle ischemia in hypertensive patients.

Full description

In 40 untreated, stage I hypertensive subjects, Investigators will measure sympathetic nerve activity (microneurography); total forearm blood flow (high-resolution ultrasonography); skeletal muscle oxygenation (Near Infrared spectroscopy); plasma F2-isoprostanes; cardiac output (non-invasive impedance plethysmography); and blood pressure at baseline and after a) rhythmic handgrip exercise at 30% of maximal voluntary contraction alone for 3 minutes, b) rhythmic handgrip at the same intensity of exercise plus lower body negative pressure (LBNP) to activate sympathetic nerve activity (SNA) for 2 minutes, and c) during intravenous infusion of Angiotensin II at the dose of 1, 2, and 3 ng/kg/min for 15 minutes at each dose.

Each subject will then be randomized to receive 12 weeks of Nebivolol (Bystolic, 5-20 mg/day) or Metoprolol Succinate (Toprol XL, 100-300 mg/day), using a randomized crossover design. There will be a 2-week washout period between the two treatment periods. During drug treatment, blood pressure will be monitored every 4 weeks and the doses of Nebivolol and Metoprolol will be titrated to keep BP <140/90 mmHg. SNA, total forearm blood flow, skeletal muscle blood flow, muscle oxygenation, cardiac output, and blood pressure responses to Nebivolol will be compared to responses during Metoprolol in the same subjects.

Enrollment: 46 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Stage I hypertension (140-159/90-99 mmHg)
• Men and women age 18-65

Exclusion criteria

• Congestive heart failure or coronary artery disease
• Blood pressure averaging >159/99 mmHg or resting heart rate < 55 bpm
• Serum creatinine > 1.4 mg/dL
• Asthma or chronic obstructive pulmonary diseases
• Left ventricular hypertrophy by echocardiography or ECG
• Pregnancy
• Hypersensitivity to beta blockers, microbubble contrast agents, or angiotensin
• Any history of substance abuse (other than tobacco)
• Concomitant drug treatment which raises endogenous nitric oxide levels such as nitrates or phosphodiesterase V inhibitors (Viagra, Levitra, or Cialis)
• History of symptomatic bradycardia or heart block

Trial design

Primary purpose: Diagnostic

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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46 participants in 2 patient groups

Initial treatment with metoprolol

Active Comparator group

Description:

The subject will be started on metoprolol succinate (Toprol XL) 100-300mg daily, which he or she will continue for a period of 12 weeks. Following the 12-week treatment period, the procedures listed below will be performed. After completion of the study procedures, the medication will be discontinued. There will be a 2-week washout period. Following washout, the subject will be started on nebivolol (Bystolic) 5-20mg daily, which he or she will continue for a period of 12 weeks. Following the 12-week treatment period, the procedures listed below will be performed. After completion of the study procedures, the medication will be discontinued.

Treatment:

Drug: Angiotensin II

Drug: Nebivolol

Procedure: Microneurography

Procedure: Rhythmic handgrip exercise

Drug: Metoprolol succinate

Procedure: Forearm blood flow

Procedure: Lower body negative pressure

Initial treatment with nebivolol

Active Comparator group

Description:

The subject will be started on nebivolol (Bystolic) 5-20mg daily, which he or she will continue for a period of 12 weeks. Following the 12-week treatment period, the procedures listed below will be performed. After completion of the study procedures, the medication will be discontinued. There will be a 2-week washout period. Following washout, the subject will be started on metoprolol succinate (Toprol XL) 100-300mg daily, which he or she will continue for a period of 12 weeks. Following the 12-week treatment period, the procedures listed below will be performed. After completion of the study procedures, the medication will be discontinued.

Treatment:

Drug: Angiotensin II

Drug: Nebivolol

Procedure: Microneurography

Procedure: Rhythmic handgrip exercise

Drug: Metoprolol succinate

Procedure: Forearm blood flow

Procedure: Lower body negative pressure