Comparison of Nebivolol and Metoprolol With Exercise and Angiotensin II in Hypertensive Patients
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ClinicalTrials.gov Identifier: NCT01502787 |
Recruitment Status :
Completed
First Posted : January 2, 2012
Results First Posted : December 31, 2014
Last Update Posted : July 7, 2020
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Hypertension | Drug: Metoprolol succinate Drug: Nebivolol Procedure: Forearm blood flow Procedure: Microneurography Procedure: Rhythmic handgrip exercise Procedure: Lower body negative pressure Drug: Angiotensin II | Phase 4 |
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.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 46 participants |
Allocation: | Randomized |
Intervention Model: | Crossover Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Diagnostic |
Official Title: | Effects of Nebivolol Versus Metoprolol on Blood Flow Responses to Exercise and Angiotensin II in Hypertensive Patients |
Study Start Date : | April 2009 |
Actual Primary Completion Date : | June 2013 |
Actual Study Completion Date : | June 2013 |

Arm | Intervention/treatment |
---|---|
Active Comparator: Initial treatment with metoprolol
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.
|
Drug: Metoprolol succinate
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.
Other Name: Toprol XL Drug: Nebivolol 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.
Other Name: Bystolic Procedure: Forearm blood flow Using high-resolution ultrasound, investigators will measure skeletal muscle blood flow in the forearm at rest, following handgrip exercise (described below), and following Angiotensin II infusion (described below). Procedure: Microneurography Investigators will measure sympathetic nerve activity from the peroneal nerve by inserting a tiny needle directly into the nerve in the leg. Investigators will localize the nerve by electrical stimulation over the skin using a blunt probe. With this stimulation, subject will notice either involuntary twitching or a tingling sensation, which may be annoying but not painful. Investigators will then introduce a tiny, sterile wire needle (an electrode) through the skin at the same location. When the tip of the needle enters the nerve, subjects may again notice involuntary muscle twitches or tingling in the leg. Investigators will then turn the electrical stimulator off and make minor adjustments in the position of the needle until investigators begin to record the nerve signals. The recording needle will remain in position throughout the study.
Other Name: Assessment of sympathetic nerve activity (SNA) Procedure: Rhythmic handgrip exercise Subjects will perform a rhythmic handgrip exercise at 30% of maximal voluntary contraction for 3 minutes. Investigators will measure cardiac output (non-invasive impedance plethysmography), blood pressure, and sympathetic nerve activity (SNA) at baseline and following this handgrip exercise. Procedure: Lower body negative pressure Lower body negative pressure increases sympathetic nerve activity. Therefore, investigators will measure cardiac output (non-invasive impedance plethysmography), blood pressure and sympathetic nerve activity at baseline and after rhythmic handgrip exercise plus lower body negative pressure (LBNP) for 2 minutes.
Other Name: LBNP Drug: Angiotensin II Investigators will measure cardiac output (non-invasive impedance plethysmography), blood pressure and sympathetic nerve activity at baseline and during intravenous infusion of Angiotensin II at the dose of 1, 2, and 3 ng/kg/min for 15 minutes at each dose.
Other Name: IND #103,935 |
Active Comparator: Initial treatment with nebivolol
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.
|
Drug: Metoprolol succinate
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.
Other Name: Toprol XL Drug: Nebivolol 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.
Other Name: Bystolic Procedure: Forearm blood flow Using high-resolution ultrasound, investigators will measure skeletal muscle blood flow in the forearm at rest, following handgrip exercise (described below), and following Angiotensin II infusion (described below). Procedure: Microneurography Investigators will measure sympathetic nerve activity from the peroneal nerve by inserting a tiny needle directly into the nerve in the leg. Investigators will localize the nerve by electrical stimulation over the skin using a blunt probe. With this stimulation, subject will notice either involuntary twitching or a tingling sensation, which may be annoying but not painful. Investigators will then introduce a tiny, sterile wire needle (an electrode) through the skin at the same location. When the tip of the needle enters the nerve, subjects may again notice involuntary muscle twitches or tingling in the leg. Investigators will then turn the electrical stimulator off and make minor adjustments in the position of the needle until investigators begin to record the nerve signals. The recording needle will remain in position throughout the study.
Other Name: Assessment of sympathetic nerve activity (SNA) Procedure: Rhythmic handgrip exercise Subjects will perform a rhythmic handgrip exercise at 30% of maximal voluntary contraction for 3 minutes. Investigators will measure cardiac output (non-invasive impedance plethysmography), blood pressure, and sympathetic nerve activity (SNA) at baseline and following this handgrip exercise. Procedure: Lower body negative pressure Lower body negative pressure increases sympathetic nerve activity. Therefore, investigators will measure cardiac output (non-invasive impedance plethysmography), blood pressure and sympathetic nerve activity at baseline and after rhythmic handgrip exercise plus lower body negative pressure (LBNP) for 2 minutes.
Other Name: LBNP Drug: Angiotensin II Investigators will measure cardiac output (non-invasive impedance plethysmography), blood pressure and sympathetic nerve activity at baseline and during intravenous infusion of Angiotensin II at the dose of 1, 2, and 3 ng/kg/min for 15 minutes at each dose.
Other Name: IND #103,935 |
- Forearm Blood Flow [ Time Frame: 12 weeks after each specified medication ]
- Blood Pressure During Exercise [ Time Frame: 12 weeks ]
- Blood Pressure During Angiotensin II Infusion [ Time Frame: 12 weeks after initiation of metoprolol ]

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Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01502787
United States, Texas | |
UT Southwestern Medical Center | |
Dallas, Texas, United States, 75390 |
Principal Investigator: | Wanpen Vongpatanasin, MD | UT Southwestern Medical Center |
Documents provided by University of Texas Southwestern Medical Center:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | University of Texas Southwestern Medical Center |
ClinicalTrials.gov Identifier: | NCT01502787 |
Other Study ID Numbers: |
STU 062011-072 |
First Posted: | January 2, 2012 Key Record Dates |
Results First Posted: | December 31, 2014 |
Last Update Posted: | July 7, 2020 |
Last Verified: | July 2020 |
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 |
Hypertension Vascular Diseases Cardiovascular Diseases Metoprolol Nebivolol Angiotensin II Giapreza Angiotensinogen 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 Vasoconstrictor Agents Serine Proteinase Inhibitors Protease Inhibitors Enzyme Inhibitors |