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

NCT01502787 | Completed Phase 4 Results DMC

• 1 other identifier: STU 062011-072
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Forearm Blood Flow

  12 weeks after each specified medication

Secondary Outcomes (2)

• Blood Pressure During Exercise

  12 weeks

• Blood Pressure During Angiotensin II Infusion

  12 weeks after initiation of metoprolol

Study Arms (2)

Initial treatment with metoprolol

ACTIVE COMPARATOR

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

Initial treatment with nebivolol

ACTIVE COMPARATOR

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

Interventions

Metoprolol succinate DRUG

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.

Also known as: Toprol XL

Initial treatment with metoprolol; Initial treatment with nebivolol

Nebivolol DRUG

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.

Also known as: Bystolic

Initial treatment with metoprolol; Initial treatment with nebivolol

Forearm blood flow PROCEDURE

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).

Initial treatment with metoprolol; Initial treatment with nebivolol

Microneurography PROCEDURE

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.

Also known as: Assessment of sympathetic nerve activity (SNA)

Initial treatment with metoprolol; Initial treatment with nebivolol

Rhythmic handgrip exercise PROCEDURE

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.

Initial treatment with metoprolol; Initial treatment with nebivolol

Lower body negative pressure PROCEDURE

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.

Also known as: LBNP

Initial treatment with metoprolol; Initial treatment with nebivolol

Angiotensin II DRUG

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.

Also known as: IND #103,935

Initial treatment with metoprolol; Initial treatment with nebivolol

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• Forest Laboratories: collaborator

Study Sites (1)

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Related Publications (19)

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• Price A, Raheja P, Wang Z, Arbique D, Adams-Huet B, Mitchell JH, Victor RG, Thomas GD, Vongpatanasin W. Differential effects of nebivolol versus metoprolol on functional sympatholysis in hypertensive humans. Hypertension. 2013 Jun;61(6):1263-9. doi: 10.1161/HYPERTENSIONAHA.113.01302. Epub 2013 Apr 1.

  PMID: 23547240 DERIVED

MeSH Terms

Conditions

Hypertension

Interventions

Metoprolol; Nebivolol; Lower Body Negative Pressure; Angiotensin II

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Ethanolamines; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Decompression; Therapeutics; Angiotensins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Autacoids; Inflammation Mediators; Biological Factors

Results Point of Contact

• Title: Wanpen Vongpatanasin
• Organization: University of Texas Southwestern Medical Center

wanpen.vongpatanasin@utsouthwestern.edu

2146458000

Study Officials

• Wanpen Vongpatanasin, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2011
• First Posted: January 2, 2012
• Study Start: April 1, 2009
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: July 7, 2020
• Results First Posted: December 31, 2014

Record last verified: 2020-07

Locations

US (1)