Nebivolol, Lifestyle Modification and Arterial Stiffness

NCT01920282 | Completed Phase 4 Results DMC

• 1 other identifier: nebstiff
• Study Type: interventional
• Target: 45
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Hypertension

Outcome Measures

Primary Outcomes (1)

• Beta-stiffness Index

  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.

  12 weeks

Secondary Outcomes (1)

• Insulin Sensitivity (HOMA-IR)

  12 weeks

Other Outcomes (1)

• Oxidized LDL Concentration

  12 weeks

Study Arms (3)

Nebivolol

ACTIVE COMPARATOR

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.

Drug: Nebivolol

Lifestyle Modification

ACTIVE COMPARATOR

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.

Other: Lifestyle Modification

Nebivolol plus Lifestyle Modification

EXPERIMENTAL

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.

Other: Nebivolol plus Lifestyle Modification

Interventions

Nebivolol DRUG

Also known as: Bystolic

Nebivolol

Lifestyle Modification OTHER

Also known as: Weight loss, Sodium restriction, Physical activity

Lifestyle Modification

Nebivolol plus Lifestyle Modification OTHER

Also known as: Bsytolic, Weight Loss, Sodium restriction, Physical activity

Nebivolol plus Lifestyle Modification

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Stage 1 hypertension
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Virginia Polytechnic Institute and State University: lead
• Forest Laboratories: collaborator

MeSH Terms

Conditions

Hypertension

Interventions

Nebivolol; Exercise

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Results Point of Contact

• Title: Dr. Kevin Davy
• Organization: Virginia Tech

kdavy@vt.edu

(540) 231-3487

Study Officials

• Kevin P Davy, Ph.D.

  Virginia Polytechnic Institute and State University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 18, 2013
• First Posted: August 9, 2013
• Study Start: January 1, 2010
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: February 23, 2018
• Results First Posted: March 2, 2016

Record last verified: 2018-01