HypertensionPhase 4NCT01961323
Effect of Nebivolol on the Blood Flow in Hearts of Adults With High Blood Pressure and Abnormal Filling of Heart
A Phase 4 study testing Nebivolol in people with Hypertension and Left Ventricular Diastolic Dysfunction, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
Trial summary
To investigate whether treatment with Nebivolol in subjects with high blood pressure and abnormal filling of left ventricle (LVDD) improves exercise time by improving Left Ventricular deformation and filling. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypertension, Left Ventricular Diastolic Dysfunction
- What is being tested?
- Nebivolol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2012to Mar 2016
- Phase
- Phase 4
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- History of mild (140-160 / 90-100) to moderate (160-200 / 100-120) hypertension
- LV diastolic dysfunction (>/= Grade1)
- LV ejection fraction >50%
- Indexed left atrial volume >/= 28 mL/m^2
- In sinus rhythm at the time of enrollment
- Willingness to return for the 6-month follow up investigations
Who cannot join
- Presence or history of any of the following at baseline:
- History of mitral valve disease of greater than mild severity or prosthetic mitral valve, congenital heart disease or permanent pacemaker
- Calculated creatinine clearance <50 mL/min
- Terminal Illness with expected Survival of <1 year
- Previous Heart Transplant
- Individuals who are institutionalized
Show all 22Show fewer
- Systolic BP>180 mm Hg or diastolic BP > 120 mm Hg
- Medical treatment for elevated BP with:
- Calcium channel blocker (e.g. verapamil, nifedipine);
- Alpha blocker (e.g. prazosin);
- Alpha agonist (e.g. α-methyldopa, hydralazine, clonidine)
- Patient unwilling or unable to provide informed consent for study participation
- Pregnancy (current, or anticipated within the study period)
- Secondary Hypertension
- Previous echo contrast allergy
- Poor echocardiography window
- Previous stroke, known carotid stenosis
- Contraindication for beta-blocker therapy (sinus bradycardia <50 beats/min);
- 2nd or 3rd degree AV conduction block
- Overt congestive cardiac failure (NYHA Class III-IV)
- Known bronchospastic disease
- Known hepatic dysfunction (SGOT/PT > twice above normal levels)
Trial locations and contacts
1 site in 1 country.
United States1 site
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
About this study
Official title: Effects of Nebivolol on Left Ventricular and Left Atrial Morphodynamics in Adults With Hypertension and Isolated Diastolic Dysfunction
To investigate whether treatment with Nebivolol in subjects with high blood pressure and abnormal filling of left ventricle (LVDD) improves exercise time by improving Left Ventricular deformation and filling.
Read the detailed description
Background:
The left ventricle (LV) ejects blood with a wringing motion, where the LV apex rotates counterclockwise and the base rotates in clockwise directions respectively. Rapid untwisting and recoil of LV during isovolumic relaxation and early diastole releases energy stored in ejection for LV suction and rapid early diastolic restoration. The LV geometry and its rotational mechanics also give rise to intracavitary blood flow rotation resulting into LV intracavitary vortex ring formation. LV torsion and vortex ring formation confer morphodynamic advantages that gain importance as blood flow velocities, heart rate and rates of change of momentum increase with exertion for improving LV efficiency. We have recently characterized the significance of LV twist mechanics and vortex ring formation in human hearts using novel high resolution speckle and contrast particle tracking echocardiography. Although data on a favorable effect of nebivolol on exercise capacity and LV diastolic filling exists, the changes in left ventricular (LV) rotational mechanics and blood flow vortex ring formation that may explain the potential hemodynamic benefits seen with nebivolol have not been previously characterized.
Aims:
In patients with hypertension and left ventricular diastolic dysfunction (LVDD) treatment with nebivolol for 6 months improves exercise time by enhancing:
- LV deformation, torsion and untwisting mechanics
- LA-to-LV blood flow transport and characteristics of intra-cavitary vortex formation
- LA reservoir and booster pump function and LA-LV interaction during the conduit phase
Hypotheses:
Treatment with nebivolol in subjects with hypertension and LVDD improves exercise time by improving LV deformation and diastolic filling. As diastole shortens with the tachycardia associated with exercise, the contribution of untwist becomes relatively more important to LV suction and filling. Nebivolol improves LV diastolic filling primarily by enhancing LV untwisting and the rheological efficiency of blood flow transport through vortex formation in early diastole.
Significance:
Patients with LVDD are asymptomatic at rest and often but become markedly symptomatic with exertion. This pilot study will provide data for the first time for correlating the improvement in exercise capacity seen with the use of nebivolol with the changes in LV relaxation, torsional mechanics, LV vortex formation and LA-LV transport functions. The preliminary data will be essential for understanding the underlying pathophysiological mechanisms through which nebivolol improves exercise hemodynamics besides providing data for development of subsequent larger randomized multicentric trials.
- Being tested
- Nebivolol
- Keywords
- Hypertension, high blood pressure, stress echocardiogram, nebivolol, left ventricular diastolic dysfunction
- Medical subject headings
- Hypertension, Ventricular Dysfunction, Left
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NebivololDrug
Doses will be titrated based on weekly visits during the first 2 weeks to achieve a target SBP<140 and DBP <90 mm Hg. If BP remains uncontrolled after 2 weeks of treatment, indapamide will be added at a dosage of 2.5 mg/day. If the therapeutic goal is still not achieved by 4 weeks, patients will be withdrawn from the study.Upward titration will be halted, and the previous dosage level resumed, if at any point systolic blood pressure falls to ≤ 100 mmHg, even if the individual remains asymptomatic.
| Study group | Role | What they receive |
|---|---|---|
| Nebivolol | Experimental | Nebivolol 5 mg (titrated to a maximal dose of 10mg for optimal blood pressure) for 6 months Receives: Drug: Nebivolol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement in Exercise Tolerance
measured by stress echocardiogram, number of participants who had improvement in METS and improvement in exercise time as compared to their baseline.
Measured: at 6 months
Secondary outcomes (2)
E Velocity Indexed to e' (E/e' Ratio) of the Left Ventricle
measured as a part of stress echocardiogram, E/e' ratio: The normal E/e' ratio from the medial annulus is <8 and suggests a normal left atrial pressure. While values between 8 and 12 are indeterminate, a value >12 is indicative of an elevated left atrial pressure or PCWP (>18mmHg). The ranges for E/e' from the lateral mitral annulus are <5, 5 -10 and >10 respectively.
Measured: at 6 months
Untwist Rate of the Left Ventricle
measured as a part of stress echocardiogram, number of participants with significant improvement in the LV untwist after Nebivolol treatment in patients who completed the study
Measured: at 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Oct 2013 (estimated)
- Study startMar 2012
- Primary completionMar 2016
- Study completionMar 2016
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.
- Other trials for HypertensionStudies of the same condition, open and under way.
- More trials run by Icahn School of Medicine at Mount SinaiThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Icahn School of Medicine at Mount Sinai
- Sponsor type
- University, hospital or other
- Collaborators
- Forest Laboratories
- Responsible party
- Principal investigator, Partho Sengupta, Icahn School of Medicine at Mount Sinai
- Investigators
- Partho Sengupta, MD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01961323
- Sponsor's protocol ID
- GCO 12-0493
- Status last verified
- Oct 2017
- First submitted
- 9 Oct 2013
- Last updated
- 24 Nov 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Nebivolol on Left Ventricular and Left Atrial Morphodynamics in Adults With Hypertension and Isolated Diastolic Dysfunction
- ClinicalTrials.gov ID
- NCT01961323
- Acronym / sponsor ID
- GCO 12-0493
- Keywords
- Hypertension, high blood pressure, stress echocardiogram, nebivolol, left ventricular diastolic dysfunction
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Icahn School of Medicine at Mount SinaiUniversity, hospital or other
- Collaborators
- Forest Laboratories
- Study start
- Mar 2012
- Primary completion
- Mar 2016 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 11 Oct 2013 (estimated)
- Results
- Posted 24 Nov 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To investigate whether treatment with Nebivolol in subjects with high blood pressure and abnormal filling of left ventricle (LVDD) improves exercise time by improving Left Ventricular deformation and filling.
Detailed description
Background:
The left ventricle (LV) ejects blood with a wringing motion, where the LV apex rotates counterclockwise and the base rotates in clockwise directions respectively. Rapid untwisting and recoil of LV during isovolumic relaxation and early diastole releases energy stored in ejection for LV suction and rapid early diastolic restoration. The LV geometry and its rotational mechanics also give rise to intracavitary blood flow rotation resulting into LV intracavitary vortex ring formation. LV torsion and vortex ring formation confer morphodynamic advantages that gain importance as blood flow velocities, heart rate and rates of change of momentum increase with exertion for improving LV efficiency. We have recently characterized the significance of LV twist mechanics and vortex ring formation in human hearts using novel high resolution speckle and contrast particle tracking echocardiography. Although data on a favorable effect of nebivolol on exercise capacity and LV diastolic filling exists, the changes in left ventricular (LV) rotational mechanics and blood flow vortex ring formation that may explain the potential hemodynamic benefits seen with nebivolol have not been previously characterized.
Aims:
In patients with hypertension and left ventricular diastolic dysfunction (LVDD) treatment with nebivolol for 6 months improves exercise time by enhancing:
- LV deformation, torsion and untwisting mechanics
- LA-to-LV blood flow transport and characteristics of intra-cavitary vortex formation
- LA reservoir and booster pump function and LA-LV interaction during the conduit phase
Hypotheses:
Treatment with nebivolol in subjects with hypertension and LVDD improves exercise time by improving LV deformation and diastolic filling. As diastole shortens with the tachycardia associated with exercise, the contribution of untwist becomes relatively more important to LV suction and filling. Nebivolol improves LV diastolic filling primarily by enhancing LV untwisting and the rheological efficiency of blood flow transport through vortex formation in early diastole.
Significance:
Patients with LVDD are asymptomatic at rest and often but become markedly symptomatic with exertion. This pilot study will provide data for the first time for correlating the improvement in exercise capacity seen with the use of nebivolol with the changes in LV relaxation, torsional mechanics, LV vortex formation and LA-LV transport functions. The preliminary data will be essential for understanding the underlying pathophysiological mechanisms through which nebivolol improves exercise hemodynamics besides providing data for development of subsequent larger randomized multicentric trials.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nebivolol | Experimental | Drug: NebivololNebivolol 5 mg (titrated to a maximal dose of 10mg for optimal blood pressure) for 6 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- History of mild (140-160 / 90-100) to moderate (160-200 / 100-120) hypertension
- LV diastolic dysfunction (>/= Grade1)
- LV ejection fraction >50%
- Indexed left atrial volume >/= 28 mL/m^2
- In sinus rhythm at the time of enrollment
Key exclusion criteria (22 listed)
- Presence or history of any of the following at baseline:
- Medical treatment for elevated BP with:
- Patient unwilling or unable to provide informed consent for study participation
- Pregnancy (current, or anticipated within the study period)
- Secondary Hypertension
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 |
|---|---|---|
| NebivololDoses will be titrated based on weekly visits during the first 2 weeks to achieve a target SBP<140 and DBP <90 mm Hg. If BP remains uncontrolled after 2 weeks of treatment, indapamide will be added at a dosage of 2.5 mg/day. If the therapeutic goal is still not achieved by 4 weeks, patients will be withdrawn from the study.Upward titration will be halted, and the previous dosage level resumed, if at any point systolic blood pressure falls to ≤ 100 mmHg, even if the individual remains asymptomatic. | Drug | Nebivolol |
Primary outcome
Improvement in Exercise Tolerance
Time frame: at 6 months
measured by stress echocardiogram, number of participants who had improvement in METS and improvement in exercise time as compared to their baseline.
2 secondary outcomes
E Velocity Indexed to e' (E/e' Ratio) of the Left Ventricle
Time frame: at 6 months
Untwist Rate of the Left Ventricle
Time frame: at 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Nov 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Partho Sengupta, MD principal investigator
Icahn School of Medicine at Mount Sinai
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Nebivolol in people with Hypertension and Left Ventricular Diastolic Dysfunction, run by Icahn School of Medicine at Mount Sinai 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 6 inclusion and 22 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 24 Nov 2017. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Nov 2017). 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?
Improvement in Exercise Tolerance (time frame: at 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Nov 2017.