Nebivolol in the Supine Hypertension of Autonomic Failure

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Forest Laboratories
Information provided by (Responsible Party):
Italo Biaggioni, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT01044693
First received: January 6, 2010
Last updated: June 20, 2013
Last verified: June 2013
  Purpose

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
Hypertension
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:
  • The fall in systolic blood pressure, measured from 8 pm to 8 am, after a single dose of nebivolol [ Time Frame: 8 pm - 8 am ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Urinary volume [ Time Frame: 8 pm - 8 am ] [ Designated as safety issue: No ]
  • SBP and DBP 1 minute post standing the following morning [ Time Frame: after 1 min ] [ Designated as safety issue: No ]
  • The mean score of Item 1 of the Orthostatic Hypotension Symptom Assessment (OHSA) taken after standing morning following the study [ Time Frame: after 5 min standing or as long as tolerated ] [ Designated as safety issue: No ]

Estimated Enrollment: 18
Study Start Date: January 2010
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (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 Drug: metoprolol tartrate 50 mg
metoprolol tartrate 50 mg single oral dose
Other Name: Lopressor
Active Comparator: Sildenafil 25 mg 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).

  Eligibility

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

Inclusion Criteria:

  • Male or female and aged 18 years or over.
  • Clinical diagnosis of orthostatic hypotension associated with Primary Autonomic Failure (PD, MSA and PAF).
  • 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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01044693

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

Additional Information:
Publications:
Responsible Party: Italo Biaggioni, Professor of Medicine and Pharmacology, Vanderbilt University
ClinicalTrials.gov Identifier: NCT01044693     History of Changes
Other Study ID Numbers: 091252
Study First Received: January 6, 2010
Last Updated: June 20, 2013
Health Authority: United States: Institutional Review Board

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

Additional relevant MeSH terms:
Multiple System Atrophy
Shy-Drager Syndrome
Atrophy
Autonomic Nervous System Diseases
Nervous System Diseases
Central Nervous System Diseases
Hypotension
Peripheral Nervous System Agents
Respiratory System Agents
Hypertension
Pure Autonomic Failure
Vascular Diseases
Cardiovascular Diseases
Primary Dysautonomias
Basal Ganglia Diseases
Brain Diseases
Movement Disorders
Neurodegenerative Diseases
Pathological Conditions, Anatomical
Metoprolol
Nebivolol
Metoprolol succinate
Nitric Oxide
Sildenafil
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Antihypertensive Agents
Sympatholytics

ClinicalTrials.gov processed this record on July 26, 2014