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Hypertension | Effects of Nebivolol on Skeletal Muscle During Exercise in Hypertensive Patients

Hypertension research study

What is the primary objective of this study?

The purpose of this study is to determine if Nebivolol improves microvascular perfusion in skeletal muscle during exercise in hypertensive patients and whether this improvement is accompanied by reduction in vascular oxidative stress or increased endothelial nitric oxide synthase (eNOS) expression in humans.

Who is eligible to participate?

Inclusion Criteria: - Men and women with stage I primary untreated hypertension (BP between 140-159/90-99 mmHg) - Age 18-65 Exclusion Criteria: - Congestive heart failure - Coronary artery disease - Left ventricular hypertrophy by echocardiography or ECG - History of stroke - Average blood pressure >159/99 mmHg - Bradycardia with a resting heart rate <55 bpm - Chronic kidney disease with a serum creatinine > 1.4 mg/dL - Asthma or chronic obstructive pulmonary disease - Women who are pregnant or planning to become pregnant - Hypersensitivity to beta blockers, hydrochlorothiazide, or Definity - Any history of substance abuse (other than tobacco) - Concomitant drug treatment which raises endogenous nitric oxide levels, including nitrates or phosphodiesterase V inhibitors (Viagra, Levitra) - History of symptomatic bradycardia or heart block - Patients with Right-to-left, bidirectional, or transient right-to-left cardiac shunts - Hypersensitivity to perflutren, blood, blood products or albumin.

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?

Hypertension

Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.

Drug:Metoprolol succinateThe 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:NebivololThe 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.

Procedure:Non-invasive measurement of Cardiac Output (CO)Cardiac Output (CO) will be measured non-invasively at rest and during exercise by thoracic electrical bioimpedance. Stroke volume will be derived from change in impedance/time measured during electrical systole. Cardiac output will be determined as the product of stroke volume and heart rate.

Procedure:Endothelial cell collectionWe will collect endothelial cells from a superficial vein, usually in the arm. Following insertion of a peripheral intravenous (IV) catheter, we will collect cells from the inner lining of the vein using a thin, flexible J-tipped wire. The wire will be inserted through the IV into the vein and then removed, along with a sampling of endothelial cells. The cells collected will be processed and stained for several proteins involved in endothelial cell function, using immunofluorescent technique.

Procedure:Microvascular perfusion assessment using DefinityUsing high-resolution ultrasound, we will measure skeletal muscle blood flow during infusion of a solution containing the octafluoropropane microbubble contrast agent, Definity. The solution will be a dilution of 1 vial of Definity to 30 cc of normal saline. The ultrasound probe will be placed over the forearm to obtain images while octafluoropropane microbubbles (Definity) are infused intravenously at the rate of 0.20 to 0.27 ml/min, not to exceed a maximum dose of 2 vials per study subject per day or visit. The microvascular perfusion assessment using Definity be performed at rest as well as during slow and fast handgrip exercises.

Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

Initial treatment with metoprololThe subject will be started on metoprolol succinate (Toprol XL) 100-300mg daily, which he/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. If necessary, 2 weeks after drug withdrawal, subjects will be started on HCTZ if BP > 140/90 mmHg and will continue HCTZ for a 2-week period, after which the subject will be transitioned to 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.

Initial treatment with nebivololThe 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. If necessary, 2 weeks after drug withdrawal, subject will be started on HCTZ if BP > 140/90 mmHg and will continue HCTZ for a 2-week period, after which the subject will be transitioned to 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.

Study Status

Completed

Start Date: August 2010

Completed Date: December 2015

Phase: Phase 4

Type: Interventional

Design:

Primary Outcome: Endothelial Cell Protein Expression p47phox From Endothelial Cell Collection

Secondary Outcome:

Study sponsors, principal investigator, and references

Principal Investigator: Wanpen Vongpatanasin, MD

Lead Sponsor: University of Texas Southwestern Medical Center

Collaborator: Forest Laboratories

More information:https://clinicaltrials.gov/show/NCT01501929

Hamada M, Kazatani Y, Shigematsu Y, Ito T, Kokubu T, Ishise S. Enhanced blood pressure response to isometric handgrip exercise in patients with essential hypertension: effects of propranolol and prazosin. J Hypertens. 1987 Jun;5(3):305-9.

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