Comparative Effects of Nebivolol Versus Placebo on Sodium Sensitivity of Blood Pressure in Hispanic Postmenopausal Women With Hypertension

Condition(s) targeted: Hypertension

Intervention: nebivolol (Drug); Nebivolol (Drug)

Phase: Phase 4

Status: Not yet recruiting

Sponsored by: University of Miami

2. 1 Research objectives:

The objective of this randomized, placebo-controlled, 2 period crossover clinical trial is to determine the effects of nebivolol versus placebo 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.

2. 1.1 Hypothesis:

Nebivolol will result in a blunted response of blood pressure to oral sodium administration and improved handling of an intravenous sodium load in comparison with placebo in hypertensive postmenopausal women.

2. 2 Research plan:

2. 2.1 Study design

The study will consist of a randomized crossover trial of the effects on salt sensitivity of nebivolol. All study procedures will be 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.

2. 2.2 Primary endpoints:

1. Change and percentage change in systolic, diastolic and mean blood pressure by ABPM from final day of low sodium to the final day of high sodium in nebivolol versus placebo

2. Differences in renal sodium excretion in response to an acute sodium load during treatment with either nebivolol or placebo.

2. 2.3 Secondary endpoints

1. Change in clinic blood pressure following 4 weeks of outpatient nebivolol versus placebo

2. Change in weight from final day of low sodium to the final day of high sodium in nebivolol versus placebo

3. Change in 24-hour sodium and potassium excretion from last day of low sodium to last day of high sodium

4. Asymmetrical dimethylarginine (ADMA)

Official title: Comparative Effects of Nebivolol Versus Placebo on Sodium Sensitivity of Blood Pressure in Hispanic Postmenopausal Women With Hypertension

Study design: Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome:

Change and percentage change in systolic, diastolic and mean blood pressure by ABPM from final day of low sodium to the final day of high sodium in nebivolol versus placebo

Differences in renal sodium excretion in response to an acute sodium load during treatment with either nebivolol or placebo.

Minimum age: 46 Years. Maximum age: N/A. Gender(s): Female.

Criteria:

Inclusion Criteria:

- Inclusion criteria for up to 20 participants

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 Cockroft-Gault estimated GFR of >70 ml/min

10. Signed informed consent and the ability to understand the study and its procedures

Exclusion Criteria:

- 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), ASA, 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.

Division of Clinical Pharmacology Clinical Pharmacology Research Unit (CPRU), 1500 NW 12th Ave 15-West. Miami, Florida 33136, United States; Not yet recruiting
Alberto B Alonso, MD, PA, Phone: 305-243-5625
Richard A Preston, MD, MSPH, Principal Investigator

Starting date: November 2009
Last updated: October 7, 2009