Nebivolol, Lifestyle Modification and Arterial Stiffness

Phase 4

Completed

• Conditions: Hypertension
• Interventions: Other: Lifestyle Modification; Other: Nebivolol plus Lifestyle Modification; Drug: Nebivolol

• Registration Number: NCT01920282
• Lead Sponsor: Virginia Polytechnic Institute and State University

Brief Summary

Numerous anti-hypertensive drugs have been reported to be efficacious in reducing central arterial stiffness and these effects may contribute to improved outcomes in hypertensive patients. However, the results of several studies suggest that beta-blockers may actually increase arterial stiffness. In contrast, there is limited evidence to suggest that nebivolol, a third generation beta-blocker that augments release of vascular nitric oxide, reduces central arterial stiffness in hypertensive individuals. Unfortunately, only a few studies have addressed this issue and all of these studies relied on indirect, blood pressure dependent measures of arterial stiffness. In addition, none of these studies focused on middle-aged and older, obese hypertensives, a population with accelerated arterial stiffening and at risk for cardiovascular diseases. Thus, the potential utility of nebivolol as a therapy to reduce large artery stiffness, particularly among the latter population, remains unclear.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-01
• Primary Completion: 2012-08
• Study Completion: 2012-08
• Study First Submitted: 2013-07-18
• Study First Submitted QC: 2013-08-07
• Study First Posted: 2013-08-09
• Results First Submitted: 2015-12-16
• Results First Submitted QC: 2016-02-02
• Results First Posted: 2016-03-02
• Status Verified: 2018-01
• Last Update Submitted: 2018-01-27
• Last Update Posted: 2018-02-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

• Stage 1 hypertension
• 40-75 years
• Weight stable (+/-2 kg)
• Sedentary to recreationally active
• Willing to be randomized to one of three arms
• Verbal and written consent
• Approval by medical director

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Exclusion Criteria

• Blood pressure outside stated range
• Diabetes or taking diabetes medications
• Total cholesterol >6.2 mmol/L; triglycerides >4.5 mmol/L
• Past or current ischemic heart disease, stroke, respiratory disease, endocrine or metabolic disease, neurological disease, or hematological-oncological disease
• Medications (including but not limited to antihypertensives, statins or other with anti-inflammatory actions) or antioxidant vitamins or supplements
• Known allergy or hypersensitivity to nebivolol or any of its components
• Inability to perform regular physical activity or participate in other components of lifestyle modification
• Pregnant or planning to become pregnant

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lifestyle Modification	Lifestyle Modification	Subjects will receive weekly lifestyle counseling by a registered dietitian to ensure adequate progress and compliance. Sample menus, 14-days of meal plans, and grocery shopping lists are provided to each individual. Individuals were instructed to reduce their daily caloric intake by 500-1000 calories and to perform a minimum of 150 minutes per week of moderate-intensity physical activity or 3000 steps/day above baseline levels. The diet plan conformed to the Dietary Approach to Stop Hypertension dietary guidelines emphasizing low fat dairy products, fruits and vegetable and contained 55% calories as carbohydrates, 30% calories as fat, and 15% calories as protein. Sodium consumption was set at 2,400 mg/day for all subjects.
Nebivolol plus Lifestyle Modification	Nebivolol plus Lifestyle Modification	Subjects begin with 5 mg/day of nebivolol and increase to 10 mg/day if brachial blood pressure is greater than 120/80 mmHg during the first 2 weeks of therapy. Subjects also receive weekly lifestyle counseling by a registered dietitian to ensure adequate progress and compliance. Sample menus, 14-days of meal plans, and grocery shopping lists are provided to each individual. Individuals will be instructed to reduce their daily caloric intake by 500-1000 calories and to perform a minimum of 150 min/wk of moderate-intensity physical activity or 3000 steps/day above baseline levels. The diet plan conforms to the Dietary Approaches to Stop Hypertension dietary guidelines emphasizing low fat dairy products, fruits and vegetable and contains 55% calories as carbohydrates, 30% calories as fat, and 15% calories as protein with sodium consumption set at 2,400 mg/day for all subjects.
Nebivolol	Nebivolol	Subjects will be provided with daily 5 mg of nebivolol for the first 2 weeks. Subjects receive additional daily doses of 10 mg nebivolol for the remainder of the study period. The dose remains at 5 mg per day, however, if BP falls below 110/70 during the first 2 weeks. Subjects will continue taking the drug during the 2-week follow-up period.

Primary Outcome Measures

Name	Time	Method
Beta-stiffness Index	12 weeks	Longitudinal B-mode images of the left common carotid artery diameter (1-2 cm proximal to the carotid bulb) were obtained over 15 consecutive cardiac cycles. Brachial blood pressure was measured via an automated sphygmomanometer. Quantification of systolic and diastolic carotid artery diameters were analyzed with the Vascular Research Tools 5 software program. Beta-stiffness index was calculated as: Beta = ln(P1/P0)/((D1-D0)/D0), where D0 represents the minimal diameter recorded during diastole, D1 represents the maximal diameter recorded during systole, P0 represents the pressure measured during diastole, and P1 represents the pressure measured during systole.

Secondary Outcome Measures

Name	Time	Method
Insulin Sensitivity (HOMA-IR)	12 weeks	The HOMA index was calculated as the product of plasma blood glucose and insulin divided by 22.5.