Nebivolol in the Supine Hypertension of Autonomic Failure

NCT01044693 | Completed Results

• 1 other identifier: 091252
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypertension; Pure Autonomic Failure; Multiple System Atrophy

Keywords

supine Hypertension; autonomic failure; nitric oxide; nebivolol

Outcome Measures

Primary Outcomes (1)

• Change in Systolic Blood Pressure During the Night

  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 Outcomes (3)

• Nocturnal Urinary Sodium Excretion

  8 pm - 8 am

• Orthostatic Tolerance the Following Morning

  10 min standing

• Change in Heart Rate During the Night

  8 pm - 8 am

Study Arms (4)

Placebo capsule

PLACEBO COMPARATOR

Placebo capsule

Drug: Placebo

Nebivolol 5 mg

EXPERIMENTAL

Nebivolol 5 mg capsule

Drug: Nebivolol 5 mg

Metoprolol tartrate 50 mg

ACTIVE COMPARATOR

Metoprolol tartrate 50 mg single oral dose

Drug: metoprolol tartrate 50 mg

Sildenafil 25 mg

ACTIVE COMPARATOR

Sildenafil 25 mg single oral dose

Drug: Sildenafil25 mg

Interventions

Placebo DRUG

Placebo capsule

Also known as: sugar pill

Placebo capsule

Nebivolol 5 mg DRUG

Nebivolol 5mg single oral dose

Also known as: Bystolic

Nebivolol 5 mg

metoprolol tartrate 50 mg DRUG

metoprolol tartrate 50 mg single oral dose

Also known as: Lopressor

Metoprolol tartrate 50 mg

Sildenafil25 mg DRUG

Sildenafil 25 mg single oral dose

Also known as: Viagra

Sildenafil 25 mg

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Vanderbilt University: lead
• Forest Laboratories: collaborator

Study Sites (1)

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

Related Publications (6)

• Biaggioni I, Garcia F, Inagami T, Haile V. Hyporeninemic normoaldosteronism in severe autonomic failure. J Clin Endocrinol Metab. 1993 Mar;76(3):580-6. doi: 10.1210/jcem.76.3.7680352.

  PMID: 7680352 BACKGROUND

• Cockcroft JR, Chowienczyk PJ, Brett SE, Chen CP, Dupont AG, Van Nueten L, Wooding SJ, Ritter JM. Nebivolol vasodilates human forearm vasculature: evidence for an L-arginine/NO-dependent mechanism. J Pharmacol Exp Ther. 1995 Sep;274(3):1067-71.

  PMID: 7562470 BACKGROUND

• Gamboa A, Shibao C, Diedrich A, Paranjape SY, Farley G, Christman B, Raj SR, Robertson D, Biaggioni I. Excessive nitric oxide function and blood pressure regulation in patients with autonomic failure. Hypertension. 2008 Jun;51(6):1531-6. doi: 10.1161/HYPERTENSIONAHA.107.105171. Epub 2008 Apr 21.

  PMID: 18426998 BACKGROUND

• Gupta S, Wright HM. Nebivolol: a highly selective beta1-adrenergic receptor blocker that causes vasodilation by increasing nitric oxide. Cardiovasc Ther. 2008 Fall;26(3):189-202. doi: 10.1111/j.1755-5922.2008.00054.x.

  PMID: 18786089 BACKGROUND

• Shannon J, Jordan J, Costa F, Robertson RM, Biaggioni I. The hypertension of autonomic failure and its treatment. Hypertension. 1997 Nov;30(5):1062-7. doi: 10.1161/01.hyp.30.5.1062.

  PMID: 9369256 BACKGROUND

• Tzemos N, Lim PO, MacDonald TM. Nebivolol reverses endothelial dysfunction in essential hypertension: a randomized, double-blind, crossover study. Circulation. 2001 Jul 31;104(5):511-4. doi: 10.1161/hc3001.094207.

  PMID: 11479245 BACKGROUND

MeSH Terms

Conditions

Hypertension; Pure Autonomic Failure; Multiple System Atrophy

Interventions

Sugars; Nebivolol; Metoprolol; Sildenafil Citrate

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Carbohydrates; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Phenoxypropanolamines; Propanolamines; Propanols; Sulfonamides; Amides; Sulfones; Sulfur Compounds; Piperazines; Purines

Results Point of Contact

• Title: Italo Biaggioni MD
• Organization: Vanderbilt University

italo.biaggioni@vanderbilt.edu

615-936-3420

Study Officials

• Italo Biaggioni, MD

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine and Pharmacology

Study Record Dates

• First Submitted: January 6, 2010
• First Posted: January 8, 2010
• Study Start: January 1, 2010
• Primary Completion: July 1, 2014
• Study Completion: August 1, 2014
• Last Updated: May 1, 2015
• Results First Posted: May 1, 2015

Record last verified: 2015-04

Locations

US (1)