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Nebivolol in the Supine Hypertension of Autonomic Failure

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01044693
Recruitment Status : Completed
First Posted : January 8, 2010
Results First Posted : May 1, 2015
Last Update Posted : May 1, 2015
Forest Laboratories
Information provided by (Responsible Party):
Italo Biaggioni, Vanderbilt University

Brief Summary:
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 or disease Intervention/treatment Phase
Hypertension Pure Autonomic Failure Multiple System Atrophy Drug: Placebo Drug: Nebivolol 5 mg Drug: metoprolol tartrate 50 mg Drug: Sildenafil25 mg Not Applicable

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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Official Title: Effect of Nebivolol on Blood Pressure in a Model of Hypertension Sensitive to Potentiation of Nitric Oxide Bioactivity
Study Start Date : January 2010
Actual Primary Completion Date : July 2014
Actual Study Completion Date : August 2014

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. 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

Secondary Outcome Measures :
  1. Nocturnal Urinary Sodium Excretion [ Time Frame: 8 pm - 8 am ]
    Nocturnal sodium excretion was defined as the ratio of urinary sodium to urinary creatinine.

  2. 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

  3. 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

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01044693

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United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University
Forest Laboratories
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Principal Investigator: Italo Biaggioni, MD Vanderbilt University
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Responsible Party: Italo Biaggioni, Professor of Medicine and Pharmacology, Vanderbilt University Identifier: NCT01044693    
Other Study ID Numbers: 091252
First Posted: January 8, 2010    Key Record Dates
Results First Posted: May 1, 2015
Last Update Posted: May 1, 2015
Last Verified: April 2015
Keywords provided by Italo Biaggioni, Vanderbilt University:
supine Hypertension
autonomic failure
nitric oxide
Additional relevant MeSH terms:
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Multiple System Atrophy
Shy-Drager Syndrome
Pure Autonomic Failure
Vascular Diseases
Cardiovascular Diseases
Pathological Conditions, Anatomical
Primary Dysautonomias
Autonomic Nervous System Diseases
Nervous System Diseases
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Sildenafil Citrate
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents
Anti-Arrhythmia Agents
Antihypertensive Agents
Autonomic Agents