A Study Examining the Effects of Nebivolol Compared to Atenolol on Endothelial Function
Condition: Hypertension
MeSH terms: Hypertension
Study type: Interventional
Phase: Phase 2

Summary: 
      This is a randomized, double-blind, placebo-controlled study comparing the efficacy of
      nebivolol and atenolol at improving small artery elasticity and reducing cardiovascular
      disease risk in subjects with early vascular disease. Approximately 75 subjects with
      borderline/elevated blood pressures and impaired endothelial function, as measured by
      arterial elasticity scores, will be recruited and assigned to treatment groups using a block
      randomization scheme. Patients will be randomly allocated to nebivolol, atenolol or placebo,
      and then followed for 9 months.
    

Detailed description: 
      The Rasmussen Disease Score (RDS) test panel is the chosen methodology for this study. The 10
      parameters of the RDS were selected because of their ability to quantify early structural and
      functional abnormalities in the vasculature and left ventricle which appear long before
      cardiovascular disease is present.

      The RDS tests include: large and small artery elasticity (measured by pulse contour
      analysis), resting blood pressure, mild treadmill exercise test, carotid IMT, left ventricle
      mass, ECG, retinal vasculature evaluation, as well as quantification of serum NT-proBNP, and
      microalbuminuria. Quantitative results from these tests are converted into categorical
      classifications based on values stratified by age and gender when appropriate. The
      categorical data is scored as follows: normal = 0 points, borderline = 1 point, abnormal = 2
      points. Point values from all parameters are summed to create the RDS, with values ranging
      from 0-20. Scores of 0-2 are classified as normal, 3-5 as early disease, and 6+ as advanced
      disease. Previous research has shown that the RDS is a powerful predictor of future
      cardiovascular events.

      The small artery elasticity (C2) parameter is of particular interest as it is responsive to
      changes in NO levels and is an effective and reliable predictor of future hypertension and
      other cardiovascular events. Changes in C2 will serve as the primary outcome of this study.
      Similar studies using anti-hypertensive or lipid-lowering interventions have found
      significant improvements in C2 values.

      Brachial artery flow-mediated dilation (FMD) measurements will also be measured as an index
      of endothelial function, although this method appears to be less sensitive to functional
      changes related to NO bioavailability than C2. Utilizing both FMD and C2 will allow
      comparison with previous studies and take advantage of a large sample size to further examine
      the relative sensitivity of each method for reliably measuring endothelial dysfunction.

      The duration of intervention for this study is 9 months which is the minimum time to
      adequately detect improvement in left ventricle (LV) mass values. LV mass measurements are a
      critical component of a comprehensive assessment of cardiovascular health and have improved
      within this temporal window as a result of anti-hypertensive intervention.
    

Intervention name(s): Nebivolol; atenolol; placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 5 mg daily or 10 mg daily; 25 mg daily or 50 mg daily; one tablet daily
Intervention MeSH terms: Atenolol; Nebivolol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: hypertension; prevention; endothelial function