Nebivolol in the Supine Hypertension of Autonomic Failure

Hypertension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01044693
• Other study ID #: 091252
• Status: Completed
• Phase: N/A
• First received: January 6, 2010
• Last updated: April 14, 2015
• Start date: January 2010
• Est. completion date: August 2014

Study information

• Verified date: April 2015
• Source: Vanderbilt University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: August 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator)

Related Conditions & MeSH terms

• Hypertension
• Multiple System Atrophy
• Pure Autonomic Failure
• Shy-Drager Syndrome

Intervention

Drug:
• Placebo
Placebo capsule
• Nebivolol 5 mg
Nebivolol 5mg single oral dose
• metoprolol tartrate 50 mg
metoprolol tartrate 50 mg single oral dose
• Sildenafil25 mg
Sildenafil 25 mg single oral dose

Locations

Country	Name	City	State
United States	Vanderbilt University	Nashville	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
Vanderbilt University	Forest Laboratories

Country where clinical trial is conducted

United States, 

References & 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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Nocturnal Urinary Sodium Excretion	Nocturnal sodium excretion was defined as the ratio of urinary sodium to urinary creatinine.	8 pm - 8 am	No
Secondary	Orthostatic Tolerance the Following Morning	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	No
Secondary	Change in Heart Rate During the Night	Change from baseline (8 pm) in heart rate at the time of maximal BP-lowering effect	8 pm - 8 am	No

External Links

•   Autonomic Dysfunction Center. Vanderbilt University