Clinical trial NCT01502787: Comparison of Nebivolol and Metoprolol With Exercise and Angiotensin II in Hypertensive Patients
Official title: Effects of Nebivolol Versus Metoprolol on Blood Flow Responses to Exercise and Angiotensin II in Hypertensive Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypertension
Keywords: hypertension
blood pressure
blood pressure medications
metoprolol
nebivolol
handgrip exercise
lower body negative pressure
angiotensin II
sympathetic nerve activity
flow mediated dilation
nitric oxide
microneurography
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
Collaborators: name: Forest Laboratories
First posted: 2012-01-02
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: DIAGNOSTIC

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Forearm Blood Flow
timeFrame: 12 weeks after each specified medication
Secondary outcomes:
measure: Blood Pressure During Exercise
timeFrame: 12 weeks
measure: Blood Pressure During Angiotensin II Infusion
timeFrame: 12 weeks after initiation of metoprolol
Other outcomes:
Locations:
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
Study officials:
affiliation: UT Southwestern Medical Center
name: Wanpen Vongpatanasin, MD
role: PRINCIPAL_INVESTIGATOR
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