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

Information source: University of Texas Southwestern Medical Center
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Hypertension

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

Phase: Phase 4

Status: Completed

Sponsored by: University of Texas Southwestern Medical Center

Official(s) and/or principal investigator(s):
Wanpen Vongpatanasin, MD, Principal Investigator, Affiliation: UT Southwestern Medical Center

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.

Clinical Details

Official title: Effects of Nebivolol Versus Metoprolol on Blood Flow Responses to Exercise and Angiotensin II in Hypertensive Patients

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Primary outcome:

Forearm Blood Flow

Sympathetic Nerve Activity (SNA) During Exercise

Sympathetic Nerve Activity (SNA) During Exercise

Sympathetic Nerve Activity (SNA) During Angiotensin II Infusion

Sympathetic Nerve Activity (SNA) During Angiotensin II Infusion

Secondary outcome:

Blood Pressure During Exercise

Blood Pressure During Exercise

Blood Pressure During Angiotensin II Infusion

Blood Pressure During Angiotensin II Infusion

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

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

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

Locations and Contacts

UT Southwestern Medical Center, Dallas, Texas 75390, United States
Additional Information

Related publications:

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Hansen J, Sander M, Thomas GD. Metabolic modulation of sympathetic vasoconstriction in exercising skeletal muscle. Acta Physiol Scand. 2000 Apr;168(4):489-503. Review.

Thomas GD, Sander M, Lau KS, Huang PL, Stull JT, Victor RG. Impaired metabolic modulation of alpha-adrenergic vasoconstriction in dystrophin-deficient skeletal muscle. Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):15090-5.

Thomas GD, Zhang W, Victor RG. Impaired modulation of sympathetic vasoconstriction in contracting skeletal muscle of rats with chronic myocardial infarctions: role of oxidative stress. Circ Res. 2001 Apr 27;88(8):816-23.

Chavoshan B, Sander M, Sybert TE, Hansen J, Victor RG, Thomas GD. Nitric oxide-dependent modulation of sympathetic neural control of oxygenation in exercising human skeletal muscle. J Physiol. 2002 Apr 1;540(Pt 1):377-86.

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Starting date: April 2009
Last updated: December 29, 2014

Page last updated: August 23, 2015

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