Nebivolol in the Supine Hypertension of Autonomic Failure

April 14, 2015 updated by: Italo Biaggioni, Vanderbilt University

Effect of Nebivolol on Blood Pressure in a Model of Hypertension Sensitive to Potentiation of Nitric Oxide Bioactivity

The purpose of this study is to evaluate the effect of the antihypertensive drug, nebivolol (Bystolic), compared to metoprolol (Lopressor) and sildenafil (Viagra) on blood pressure in patients with autonomic failure and supine hypertension.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Nebivolol is distinct among beta-blockers by its ability to increase nitric oxide (NO) bioactivity. The contribution of this effect to the pharmacological actions of the drug, however, is difficult to ascertain in normal subjects because of the confounding contribution of the autonomic nervous system. Autonomic failure patients provide a unique model of hypertension devoid of autonomic modulation but sensitive to NO mechanisms. We propose to determine the effect of nebivolol on blood pressure in this patient population. A decrease in blood pressure will imply increased bioactivity of NO. Comparisons will be made with placebo, metoprolol (as a negative control) and sildenafil (as a positive control).

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male or female and aged 18 years or over.
  • Clinical diagnosis of orthostatic hypotension associated with Primary Autonomic Failure (Parkinson Disease, Multiple System Atrophy and Pure Autonomic Failure).
  • A documented fall in systolic blood pressure of at least 20 mmHg, or in diastolic blood pressure of at least 10 mmHg, within 3 minutes after standing.
  • Supine hypertension, defined as a systolic blood pressure >150 mm Hg or diastolic blood pressure > 90 mm Hg.
  • Provide written informed consent to participate in the study and understand that they may withdraw their consent at any time without prejudice to their future medical care.

Exclusion Criteria:

  • Have changed dose, frequency and or type of prescribed medication, within two weeks of study start.
  • Women of childbearing potential who are not using a medically accepted contraception.
  • Have, in the investigator's opinion, any significant cardiac, systemic, hepatic, or renal illness.
  • Diabetes mellitus or insipidus.
  • In the investigator's opinion, have clinically significant abnormalities on clinical examination or laboratory testing.
  • In the investigator's opinion, are unable to adequately co-operate because of individual or family situation.
  • In the investigator's opinion, are suffering from a mental disorder that interferes with the diagnosis and/or with the conduct of the study, e.g. schizophrenia, major depression, dementia.
  • Are not able or willing to comply with the study requirements for the duration of the study.
  • Persons on drugs with beta-blocking potential (e.g., amiodarone), persons taking scheduled or as needed nitrates and persons on drugs with alpha-blocking potential (e.g. tamsulosin).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo capsule
Drug: Placebo
Placebo capsule
Other Names:
  • sugar pill
Experimental: Nebivolol 5 mg
Nebivolol 5 mg capsule
Drug: Nebivolol 5 mg
Nebivolol 5mg single oral dose
Other Names:
  • Bystolic
Active Comparator: Metoprolol tartrate 50 mg
Metoprolol tartrate 50 mg single oral dose
Drug: metoprolol tartrate 50 mg
metoprolol tartrate 50 mg single oral dose
Other Names:
  • Lopressor
Active Comparator: Sildenafil 25 mg
Sildenafil 25 mg single oral dose
Drug: Sildenafil25 mg
Sildenafil 25 mg single oral dose
Other Names:
  • Viagra

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Systolic Blood Pressure During the Night
Time Frame: 8 pm - 8 am
Maximal change from baseline in systolic blood pressure, measured from 8 pm to 8 am, after a single dose of the intervention
8 pm - 8 am

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Nocturnal Urinary Sodium Excretion
Time Frame: 8 pm - 8 am
Nocturnal sodium excretion was defined as the ratio of urinary sodium to urinary creatinine.
8 pm - 8 am
Orthostatic Tolerance the Following Morning
Time Frame: 10 min standing
Orthostatic tolerance was defined as the area under the curve of standing systolic blood pressure calculated by the trapezoidal rule (upright systolic blood pressure multiplied by standing time) during a 10-minute standing test
10 min standing
Change in Heart Rate During the Night
Time Frame: 8 pm - 8 am
Change from baseline (8 pm) in heart rate at the time of maximal BP-lowering effect
8 pm - 8 am

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vanderbilt University

Collaborators

Forest Laboratories

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2010

Primary Completion (Actual)

July 1, 2014

Study Completion (Actual)

August 1, 2014

Study Registration Dates

First Submitted

January 6, 2010

First Submitted That Met QC Criteria

January 7, 2010

First Posted (Estimate)

January 8, 2010

Study Record Updates

Last Update Posted (Estimate)

May 1, 2015

Last Update Submitted That Met QC Criteria

April 14, 2015

Last Verified

April 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 091252

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Hypertension

Clinical Trials on Placebo

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Burundi

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe