Nebivolol in the Supine Hypertension of Autonomic Failure

Not Applicable

Completed

• Conditions: Multiple System Atrophy; Hypertension; Pure Autonomic Failure
• Interventions: Drug: Placebo; Drug: Nebivolol 5 mg; Drug: metoprolol tartrate 50 mg; Drug: Sildenafil25 mg

• Registration Number: NCT01044693
• Lead Sponsor: 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.

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).

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2010-01
• Study First Submitted: 2010-01-06
• Study First Submitted QC: 2010-01-07
• Study First Posted: 2010-01-08
• Primary Completion: 2014-07
• Study Completion: 2014-08
• Status Verified: 2015-04
• Results First Submitted: 2015-04-14
• Results First Submitted QC: 2015-04-14
• Last Update Submitted: 2015-04-14
• Results First Posted: 2015-05-01
• Last Update Posted: 2015-05-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

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.

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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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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo capsule	Placebo	Placebo capsule
Nebivolol 5 mg	Nebivolol 5 mg	Nebivolol 5 mg capsule
Metoprolol tartrate 50 mg	metoprolol tartrate 50 mg	Metoprolol tartrate 50 mg single oral dose
Sildenafil 25 mg	Sildenafil25 mg	Sildenafil 25 mg single oral dose

Primary Outcome Measures

Name	Time	Method
Change in Systolic Blood Pressure During the Night	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

Name	Time	Method
Nocturnal Urinary Sodium Excretion	8 pm - 8 am	Nocturnal sodium excretion was defined as the ratio of urinary sodium to urinary creatinine.
Change in Heart Rate During the Night	8 pm - 8 am	Change from baseline (8 pm) in heart rate at the time of maximal BP-lowering effect
Orthostatic Tolerance the Following Morning	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

Trial Locations

Locations (1)

Vanderbilt University; 🇺🇸 Nashville, Tennessee, United States