HypertensionNCT01044693

Nebivolol in the Supine Hypertension of Autonomic Failure

A study testing Nebivolol 5 mg, metoprolol tartrate 50 mg and Sildenafil25 mg in people with Hypertension and Pure Autonomic Failure, run by Vanderbilt University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

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. Read more about this study

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Hypertension, Pure Autonomic Failure, Multiple System Atrophy
What is being tested?: Nebivolol 5 mg, metoprolol tartrate 50 mg and Sildenafil25 mg
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 20 participants
Where: 1 siteUnited States
Study dates: Jan 2010to Aug 2014
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Show all 9Show fewer

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).

Trial locations and contacts

1 site in 1 country.

United States1 site

Vanderbilt University
Nashville, Tennessee, 37232

Other trials in United States

About this study

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

Read the 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).

Conditions: Hypertension, Pure Autonomic Failure, Multiple System Atrophy
Being tested: Placebo, Nebivolol 5 mg, metoprolol tartrate 50 mg, Sildenafil25 mg
Keywords: supine Hypertension, autonomic failure, nitric oxide, nebivolol
Medical subject headings: Hypertension, Pure Autonomic Failure, Multiple System Atrophy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PlaceboDrug
Also called sugar pill
Placebo capsule
Nebivolol 5 mgDrug
Also called Bystolic
Nebivolol 5mg single oral dose
metoprolol tartrate 50 mgDrug
Also called Lopressor
metoprolol tartrate 50 mg single oral dose
Sildenafil25 mgDrug
Also called Viagra
Sildenafil 25 mg single oral dose

Study groups in NCT01044693
Study group	Role	What they receive
Placebo capsule	Placebo comparator	Placebo capsule Receives: Drug: Placebo
Nebivolol 5 mg	Experimental	Nebivolol 5 mg capsule Receives: Drug: Nebivolol 5 mg
Metoprolol tartrate 50 mg	Active comparator	Metoprolol tartrate 50 mg single oral dose Receives: Drug: metoprolol tartrate 50 mg
Sildenafil 25 mg	Active comparator	Sildenafil 25 mg single oral dose Receives: Drug: Sildenafil25 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 8 pm - 8 am

Secondary outcomes (3)

Nocturnal Urinary Sodium Excretion
Nocturnal sodium excretion was defined as the ratio of urinary sodium to urinary creatinine.
Measured: 8 pm - 8 am
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
Measured: 10 min standing
Change in Heart Rate During the Night
Change from baseline (8 pm) in heart rate at the time of maximal BP-lowering effect
Measured: 8 pm - 8 am

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2010Aug 2014

First posted8 Jan 2010 (estimated)
Study startJan 2010
Primary completionJul 2014
Study completionAug 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (6)Papers the sponsor has linked to this study.
Other trials for HypertensionStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 20 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01044693
Sponsor's protocol ID: 091252
Status last verified: Apr 2015
First submitted: 6 Jan 2010
Last updated: 1 May 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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.
PubMed 7680352
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.
PubMed 7562470
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.
PubMed 18426998
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.
PubMed 18786089
Shannon J, Jordan J, Costa F, Robertson RM, Biaggioni I; New Collective Author. The hypertension of autonomic failure and its treatment. Hypertension. 1997 Nov;30(5):1062-7. doi: 10.1161/01.hyp.30.5.1062.
PubMed 9369256
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.
PubMed 11479245

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 1 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effect of Nebivolol on Blood Pressure in a Model of Hypertension Sensitive to Potentiation of Nitric Oxide Bioactivity
ClinicalTrials.gov ID: NCT01044693
Acronym / sponsor ID: 091252
Conditions: Hypertension, Pure Autonomic Failure, Multiple System Atrophy
Keywords: supine Hypertension, autonomic failure, nitric oxide, nebivolol
Study type: Interventional
Recruitment status: Completed
Enrolment: 20 participants (actual)
Lead sponsor: Vanderbilt UniversityUniversity, hospital or other
Collaborators: Forest Laboratories
Study start: Jan 2010
Primary completion: Jul 2014 (actual)
Study completion: Aug 2014 (actual)
First posted: 8 Jan 2010 (estimated)
Results: Posted 1 May 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 4

Arm	Type	Receives
Placebo capsule	Placebo comparator	Drug: PlaceboPlacebo capsule
Nebivolol 5 mg	Experimental	Drug: Nebivolol 5 mgNebivolol 5 mg capsule
Metoprolol tartrate 50 mg	Active comparator	Drug: metoprolol tartrate 50 mgMetoprolol tartrate 50 mg single oral dose
Sildenafil 25 mg	Active comparator	Drug: Sildenafil25 mgSildenafil 25 mg single oral dose

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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.

Key exclusion criteria (9 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PlaceboAlso: sugar pillPlacebo capsule	Drug	Placebo capsule
Nebivolol 5 mgAlso: BystolicNebivolol 5mg single oral dose	Drug	Nebivolol 5 mg
metoprolol tartrate 50 mgAlso: Lopressormetoprolol tartrate 50 mg single oral dose	Drug	Metoprolol tartrate 50 mg
Sildenafil25 mgAlso: ViagraSildenafil 25 mg single oral dose	Drug	Sildenafil 25 mg

Primary outcome

Change in Systolic Blood Pressure During the Night
Time frame: 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

3 secondary outcomes

Nocturnal Urinary Sodium Excretion
Time frame: 8 pm - 8 am
Orthostatic Tolerance the Following Morning
Time frame: 10 min standing
Change in Heart Rate During the Night
Time frame: 8 pm - 8 am

Results and safety

Results posted to the registry on 1 May 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo Then Metoprolol Then Sildenafil Then Nebivolol	3	3
Placebo Then Nebivolol Then Metoprolol Then Sildenafil	1	1
Placebo Then Sildenafil Then Nebivolol Then Metoprolol	1	1
Placebo Then Sildenafil Then Metoprolol Then Nebivolol	1	1
Nebivolol Then Placebo Then Metoprolol Then Sildenafil	1	1
Metoprolol Then Sildenafil Then Placebo Then Nebivolol	2	2
Sildenafil Then Nebivolol Then Placebo Then Metoprolol	1	1
Metoprolol Then Placebo Then Nebivolol Then Sildenafil	1	1
Nebivolol Then Metoprolol Then Sildenafil Then Placebo	1	1
Metoprolol Then Nebivolol Then Placebo Then Sildenafil	1	1
Metoprolol Then Sildenafil Then Nebivolol Then Placebo	1	1
Sildenafil Then Nebivolol Then Metoprolol Then Placebo	1	1
Sildenafil Then Metoprolol Then Nebivolol Then Placebo	2	2
Nebivolol Then Sildenafil Then Metoprolol Then Placebo	1	1
Nebivolol Then Placebo Then Sildenafil Then Metoprolol	1	1
Placebo Then Nebivolol Then Sildenafil Then Metoprolol	1	1

Primary outcome: Change in Systolic Blood Pressure During the Night

Time frame: 8 pm - 8 am. Mean (Standard Error). Unit: mm Hg

Measure	Placebo Capsule n = 20	Nebivolol 5 mg n = 20	Metoprolol Tartrate 50 mg n = 20	Sildenafil 25 mg n = 20
Baseline supine at 8 pm	154 (7)	162 (5)	157 (5)	158 (6)
Change in systolic BP	1 (7)	-24 (9)	-7 (6)	-20 (6)

Placebo Capsule vs Nebivolol 5 mg: p = 0.036, Mixed Models Analysis
Placebo Capsule vs Sildenafil 25 mg: p <0.001, Mixed Models Analysis
Placebo Capsule vs Metoprolol Tartrate 50 mg: p >0.05, Mixed Models Analysis

Population analysed: Participants who completed the 4 treatment arms

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: 1 day for each intervention. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo Capsule	0 of 20 (0%)	0 of 20 (0%)	Not reported
Nebivolol 5 mg	0 of 20 (0%)	0 of 20 (0%)	Not reported
Metoprolol Tartrate 50 mg	0 of 20 (0%)	0 of 20 (0%)	Not reported
Sildenafil 25 mg	0 of 20 (0%)	2 of 20 (10%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 7680352Biaggioni 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.
Background: PubMed 7562470Cockcroft 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.
Background: PubMed 18426998Gamboa 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.
Background: PubMed 18786089Gupta 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.
Background: PubMed 9369256Shannon J, Jordan J, Costa F, Robertson RM, Biaggioni I; New Collective Author. The hypertension of autonomic failure and its treatment. Hypertension. 1997 Nov;30(5):1062-7. doi: 10.1161/01.hyp.30.5.1062.
Background: PubMed 11479245Tzemos 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Italo Biaggioni, MD principal investigator

Vanderbilt University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Nebivolol 5 mg, metoprolol tartrate 50 mg and Sildenafil25 mg in people with Hypertension and Pure Autonomic Failure, run by Vanderbilt University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 May 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 May 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Systolic Blood Pressure During the Night (time frame: 8 pm - 8 am). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01044693, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2015.