Nebivolol in the Supine Hypertension of Autonomic Failure

This study has been completed.
Forest Laboratories
Information provided by (Responsible Party):
Italo Biaggioni, Vanderbilt University Identifier:
First received: January 6, 2010
Last updated: April 14, 2015
Last verified: April 2015
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.

Condition Intervention
Pure Autonomic Failure
Multiple System Atrophy
Drug: Placebo
Drug: Nebivolol 5 mg
Drug: metoprolol tartrate 50 mg
Drug: Sildenafil25 mg

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Official Title: Effect of Nebivolol on Blood Pressure in a Model of Hypertension Sensitive to Potentiation of Nitric Oxide Bioactivity

Resource links provided by NLM:

Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Change in Systolic Blood Pressure During the Night [ Time Frame: 8 pm - 8 am ] [ Designated as safety issue: No ]
    Maximal change from baseline in systolic blood pressure, measured from 8 pm to 8 am, after a single dose of the intervention

Secondary Outcome Measures:
  • Nocturnal Urinary Sodium Excretion [ Time Frame: 8 pm - 8 am ] [ Designated as safety issue: No ]
    Nocturnal sodium excretion was defined as the ratio of urinary sodium to urinary creatinine.

  • Orthostatic Tolerance the Following Morning [ Time Frame: 10 min standing ] [ Designated as safety issue: No ]
    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

  • Change in Heart Rate During the Night [ Time Frame: 8 pm - 8 am ] [ Designated as safety issue: No ]
    Change from baseline (8 pm) in heart rate at the time of maximal BP-lowering effect

Enrollment: 20
Study Start Date: January 2010
Study Completion Date: August 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo capsule
Placebo capsule
Drug: Placebo
Placebo capsule
Other Name: sugar pill
Experimental: Nebivolol 5 mg
Nebivolol 5 mg capsule
Drug: Nebivolol 5 mg
Nebivolol 5mg single oral dose
Other Name: 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 Name: Lopressor
Active Comparator: Sildenafil 25 mg
Sildenafil 25 mg single oral dose
Drug: Sildenafil25 mg
Sildenafil 25 mg single oral dose
Other Name: Viagra

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).

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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).
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Please refer to this study by its identifier: NCT01044693

United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University
Forest Laboratories
Principal Investigator: Italo Biaggioni, MD Vanderbilt University
  More Information

Additional Information:
Responsible Party: Italo Biaggioni, Professor of Medicine and Pharmacology, Vanderbilt University Identifier: NCT01044693     History of Changes
Other Study ID Numbers: 091252 
Study First Received: January 6, 2010
Results First Received: April 14, 2015
Last Updated: April 14, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by Vanderbilt University:
supine Hypertension
autonomic failure
nitric oxide

Additional relevant MeSH terms:
Multiple System Atrophy
Pure Autonomic Failure
Shy-Drager Syndrome
Autonomic Nervous System Diseases
Basal Ganglia Diseases
Brain Diseases
Cardiovascular Diseases
Central Nervous System Diseases
Movement Disorders
Nervous System Diseases
Neurodegenerative Diseases
Primary Dysautonomias
Vascular Diseases
Sildenafil Citrate
Adrenergic Agents
Adrenergic Agonists
Adrenergic Antagonists
Adrenergic beta-1 Receptor Agonists
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Agonists
Adrenergic beta-Antagonists
Anti-Arrhythmia Agents
Antihypertensive Agents
Autonomic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action processed this record on May 26, 2016