Nebivolol Versus Metoprolol: Sodium Sensitivity
Condition: Hypertension
MeSH terms: Hypertension; Hypersensitivity
Intervention: nebivolol; Metoprolol
Intervention description: 5 mg titrated to 10 mg daily versus matching placebo; Metoprolol 50 mg titrated to 100 mg
Intervention MeSH terms: Metoprolol; Nebivolol
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: Female
Minimum age: 46 Years
Healthy volunteers: No

Summary:

      Research objectives

      The objective of this randomized, placebo-controlled, 2 period crossover clinical trial is to
      determine the effects of nebivolol versus metoprolol on ambulatory blood pressure, the blood
      pressure response to dietary sodium loading, and renal handling of an acute sodium load in
      postmenopausal women with hypertension.

      Hypothesis

      Nebivolol will result in a blunted response of blood pressure to oral sodium administration
      and improved renal handling of an intravenous sodium load in comparison with metoprolol in
      hypertensive postmenopausal women.

      Research plan

      Study design

      The study consisted of a randomized crossover trial of the effects on sodium sensitivity and
      renal sodium handling of nebivolol versus metoprolol. All study procedures were carried out
      under the direct supervision of the Principal Investigator in the outpatient and inpatient
      research unit of the University of Miami Division of Clinical Pharmacology.

      Primary endpoint

      Change in 24-hour mean systolic blood pressure determined by 24-hour ambulatory blood
      pressure monitor (ABPM) from the final day of low sodium to the final day of high sodium in
      nebivolol versus metoprolol
    

Eligibility criteria:

        Inclusion Criteria:

          1. Women > 45 years of age.

          2. Self-identified as Hispanic ethnicity.

          3. Have hypertension defined as:

               -  Systolic blood pressure 140-159 mm Hg off antihypertensive medications

               -  Diastolic 90-99 mm Hg off antihypertensive medications

          4. Blood pressure will be calculated as the mean of 3 consecutive office cuff
             measurements at rest (sitting). In order to be eligible for treatment, subjects must
             meet the above definition of hypertension at screening visits off antihypertensive
             medications

          5. Natural menopause at least 1 year (no menstruation for 1 year) prior to screening or
             had a bilateral oophorectomy at least 3 months prior to study participation.

          6. No clinically significant or unstable coexisting medical condition in the estimation
             of the study PI

          7. No clinically significant abnormalities of physical exam or laboratory data in the
             estimation of the PI

          8. Concomitant medications will be evaluated on a case by case basis by the study PI

          9. Renal function as assessed by a Cockcroft-Gault estimated glomerular filtration rate
             (GFR) of >70 ml/min

         10. Signed informed consent and the ability to understand the study and its procedures

        Exclusion Criteria:

          1. Inability to understand the study or provide informed consent

          2. History of adverse effects or intolerance to nebivolol or beta-blockers

          3. Previous treatment with nebivolol within the preceding six months.

          4. Significant or unstable cardiovascular, pulmonary, renal, gastrointestinal, hepatic,
             endocrine, or central nervous system as determined by the principal investigator.

          5. Clinically significant abnormalities of physical examination or laboratory data as
             determined by the principal investigator.

          6. The subject has donated or lost more than 450 mL of blood or has received transfusion
             of any blood or blood products within 30 days prior to screening.

          7. Receiving treatment with diuretics, non-steroidal anti-inflammatory drugs (NSAIDs),
             aspirin, steroids, or other agents known to influence blood pressure, renal function,
             or sodium sensitivity. Any concomitant medications will be reviewed by the study PI on
             a case-by-case basis. In general, no concomitant medication is preferred. Any
             medication may be tapered/discontinued with consent of patient and at the discretion
             of the study PI.

          8. Grapefruit and Seville oranges are not allowed at any time during the study.

          9. Any disease or condition that, in the opinion of the investigator, could compromise
             the absorption, accumulation, metabolism, or excretion of the study medication.

         10. Current alcohol or drug abuse.

         11. Smoking of more than 10 cigarettes per day.