The Effects of Nebivolol on the NO-system in Patients With Essential Hypertension (NEBI)

March 1, 2014 updated by: Erling Bjerregaard Pedersen

The Effects of Nebivolol on the NO-system in Patients With Essential

Investigators want investigate the following hypothesis:

  1. Nebivolol increases nitric oxide activity in the systemic circulation and the kidney
  2. The increased activity of nitric oxide during nebivolol treatment can be demonstrated by inhibition of NO synthesis with L-NMMA. We expect increased responses in blood pressure and sodium excretion is expected during nebivolol treatment compared to placebo.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Beta-blockers are no longer recommended as first line treatment in essential hypertension. Evidence mainly based on clinical trails with the non-vasodilating beta-blockers atenolol and propanolol points towards that beta-blockers have an increased risk of stroke compared to ACE-inhibitors, calcium channel blockers and thiazides. However, this Nebivolol is a third generation beta-blocker with vasodilating properties. Nebivolol decreases peripheral blood pressure to the same extend as other beta-blockers but in contrast to atenolol nebivolol also reduces central blood pressure. Furthermore nebivolol increases nitric oxide (NO) availability in forearm vessels, maybe through activation of beta-3 receptors. The nitric oxide system plays a central role in both renal sodium and water handling and regulation of vascular tone and blood pressure. It has not been investigated if nebivolol changes NO availability in the kidney.

Investigators want investigate the following hypothesis:

  1. Nebivolol increases nitric oxide activity in the systemic circulation and the kidney
  2. The increased activity of nitric oxide during nebivolol treatment can be demonstrated by inhibition of NO synthesis with L-NMMA. Investigators expect increased responses in blood pressure and sodium excretion is expected during nebivolol treatment compared to placebo.

Purpose The purpose of this study is to investigate the effects of nebivolol on renal handling of sodium and water (Glomerular filtration rate, urine production, free water clearance, excretion of proteins from epithelial sodium channels (u-ENaCαβγ) and aquaporin channels (u-AQP2) and sodium and potassium excretion), plasma concentrations of vasoactive hormones (renin, angiotensin II, aldosterone, vasopressin, atrial natriuretic peptide, brain natriuretic peptide and endothelin), central blood pressure, pulse wave velocity (PWV) and augmentation index, under basal conditions and during inhibition of nitric oxide synthesis in patients with essential hypertension.

Design 25 patients with essential hypertension are recruited in this randomised, cross over, placebo-controlled, double blinded study with two treatment periods (nebivolol/placebo). Each subject will attend to two examination days. Four days prior to each examination days and on the morning of each examination day subjects are given either nebivolol 5 mg pr. day or placebo. During treatment periods subject are given a standardized diet. On the examination days subject are given L-NMMA, a nitric oxide synthase inhibitor, and renal function, central hemodynamic and vasoactive hormones are evaluated during basal conditions and during inhibition of nitric oxide synthesis.

Perspectives This study is expected to contribute to increasing the knowledge about the mechanisms involved in the development and progression of cardiovascular disease. Beta-blockers are not recommended as first line treatment in essential hypertension but the results from this study may influence clinical treatment of essential hypertension in the future.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
25

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Holstebro, Denmark, 7500
        • Department of Medical Research, Holstebro Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

40 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Increased blood pressure (above 135 mmHg systolic or 85 mmHg diastolic in day time in 24 hour blood pressure measurement taking 5 or 10 mg amlodipine
  • Men and women
  • age 40 - 70 years
  • informed consent

Exclusion Criteria:

  • diabetes mellitus
  • glomerular filtration rate < 30 ml/min
  • albuminuria > 1,5 g/l
  • renogram which suggests secondary hypertension
  • clinical signs of pheochromocytoma or increased p-metanephrines
  • clinical important sign og heart, lung, liver, thyroid or neoplastic diseases
  • clinical important deviations in routine blood samples or ECG
  • drug or alcohol abuse
  • pregnancy or nursery
  • intolerance to nebivolol
  • blood donation with a month of the first examination day
  • inacceptable increase in blood pressure durin L-NMMA infusion (200/120)
  • inacceptable side effects to amlodipine
  • blood pressure increase above 170/105 on highest dose amlodipine (10 mg)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Nebivolol
Tablet Nebivolol 5 mg (oral use) for 5 days
Drug: Nebivolol
Tablet i blinded in capsula
Other Names:
  • Tradename in Denmark: Hypoloc
Placebo Comparator: Placebo
Inactive placebo given as tablet for 5 days
Drug: placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Fractional excretion of sodium
Time Frame: 5 days
5 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Blood pressure
Time Frame: 5 days
Both ambulatory blood pressure and office and central blood pressure before and during L-NMMA infusion
5 days
Pulse wave velocity
Time Frame: 5 days
before and during L-NMMA infusion
5 days
Plasma renin concentration
Time Frame: 5 days
before and during L-NMMA infusion
5 days
Plasma aldosterone concentration
Time Frame: 5 days
Before and during L-NMMA infusion
5 days
Plasma angiotensin II concentration
Time Frame: 5 days
Before and during L-NMMA infusion
5 days
Plasma Endothelin concentration
Time Frame: 5 days
Before and during L-NMMA infusion
5 days
Plasma brain natriuretic peptide concentration
Time Frame: 5 days
Before and during L-NMMA infusion
5 days
Plasma vasopressin concentration
Time Frame: 5 days
Before and during L-NMMA infusion
5 days
Glomerular filtration rate
Time Frame: 5 days
Before and during L-NMMA infusion
5 days
Urinary excretions of epithelial sodium channels
Time Frame: 5 days
Before and during L-NMMA infusion
5 days
Urinary excretions of aquaprorin-2
Time Frame: 5 days
Before and during L-NMMA infusion
5 days
24-hour ambulatory blood pressure
Time Frame: 5 days
5 days
Free water clearance
Time Frame: 5 days
Before and during L-NMMA infusion
5 days
Urine flow
Time Frame: 5 days
Before and during L-NMMA infusion
5 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Erling Bjerregaard Pedersen

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Erling B Pedersen, MD, Department of Medical Research, Holstebro Hospital
  • Principal Investigator: Frank H Mose, MD, Department of Medical Research, Holstebro Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2012

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2013

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2013

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 1, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 5, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 6, 2012

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 4, 2014

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 1, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • FHC-1-2012

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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