Impacts of Aldosterone Blockade on Myocardial Remodeling in Hypertensive Patients With Diastolic Failing Heart

September 12, 2013 updated by: National Taiwan University Hospital

Aim of study: The effects of aldosterone blockade on myocardial remodeling in hypertensive patients with diastolic failing heart remains unclarified.

Background: Nearly half of patients with clinical heart failure (HF) have normal left ventricular ejection fraction (LVEF) who usually present with apparent diastolic dysfunction (DD) and are referred as diastolic HF (DHF). The renin-angiotensin-aldosterone system is an established major pathway that is operative in the pathogenesis of HF. The effects of aldosterone on myocardial hypertrophy, fibrosis and endothelial dysfunction have clearly been established in human and animal models. Furthermore, in these models, aldosterone antagonism prevented the development of myocardial fibrosis independent of its effect on blood pressure or myocardial hypertrophy. However, its application to patients with DHF is unspecified. In the study, we hypothesize that aldosterone blockade could reverse LV remodeling process in hypertensive patients with DHF.

Study protocol: We will enroll medically well-controlled hypertensive patients who have DHF defined as the presence of exertional dyspnea or HF signs/symptoms, diastolic dysfunction as impaired tissue-Doppler (TDI) derived mitral early annular diastolic velocity (< 8 cm/s), and LVEF > 50 % in echocardiography. All patients will be randomized to receive spironolactone 25 mg per day or not for at least 6 months. At baseline before randomization and 6 months after randomization, we will investigate the Quality-of-life (QOL) score by Minnesota Living with Heart Failure questionnaire (Chinese version), echocardiography coupled with TDI to assess the degree of LV hypertrophy, myocardial systolic and diastolic characteristics. Otherwise, we draw blood sampling at baseline and after randomization for quantifying and comparing several biomarkers which are currently proved to be correlated with LV hypertrophy, myocardial fibrosis, and biomechanical stretch in DHF patients, such as N-terminal pro-brain-type natriuretic peptide, matrix metalloproteinase-2, carboxy-terminal telopeptide, procollagen type III amino-terminal propeptide, soluble ST2, and galectin-3. Expected results: Aldosterone antagonism is effective for hypertensive patients with DHF by improving the quality of life, echo-derived myocardial function, and reducing ventricular mechanical stretch through lessening the degree of LV hypertrophy and myocardial fibrosis.

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

Aim of study: The effects of aldosterone blockade on myocardial remodeling in hypertensive patients with diastolic failing heart remains unclarified. Background: Nearly half of patients with clinical heart failure (HF) have normal left ventricular ejection fraction (LVEF) who usually present with apparent diastolic dysfunction (DD) and are referred as diastolic HF (DHF). Hypertensive heart disease occurs in the majority of patients with DHF, and several key aspects of heart failure secondary to hypertensive heart disease are the relatively highly prevalent LV hypertrophy, cardiac fibrosis, and endothelial dysfunction-mediated myocardial injury caused by changes in the local and systemic neurohormonal environment, and all of which are associated with LV diastolic dysfunction and tissue-Doppler derived systolic myocardial function. The renin-angiotensin-aldosterone system is an established major pathway that is operative in the pathogenesis of HF. The effects of aldosterone on myocardial hypertrophy, fibrosis and endothelial dysfunction have clearly been established in human and animal models. Furthermore, in these models, aldosterone antagonism prevented the development of myocardial fibrosis independent of its effect on blood pressure or myocardial hypertrophy. However, its application to patients with DHF is unspecified. In the study, we hypothesize that aldosterone blockade could reverse LV remodeling process in hypertensive patients with DHF.

Study protocol: We will enroll medically well-controlled hypertensive patients who have DHF defined as the presence of exertional dyspnea or HF signs/symptoms, diastolic dysfunction as impaired tissue-Doppler (TDI) derived mitral early annular diastolic velocity (< 8 cm/s), and LVEF > 50 % in echocardiography. All patients will be randomized to receive spironolactone 25 mg per day or not for at least 6 months. At baseline before randomization and 6 months after randomization, we will investigate the Quality-of-life (QOL) score by Minnesota Living with Heart Failure questionnaire (Chinese version), echocardiography coupled with TDI to assess the degree of LV hypertrophy, myocardial systolic and diastolic characteristics. Otherwise, we draw blood sampling at baseline and after randomization for quantifying and comparing several biomarkers which are currently proved to be correlated with LV hypertrophy, myocardial fibrosis, and biomechanical stretch in DHF patients, such as N-terminal pro-brain-type natriuretic peptide, matrix metalloproteinase-2, carboxy-terminal telopeptide, procollagen type III amino-terminal propeptide, soluble ST2, and galectin-3. Expected results: Aldosterone antagonism is effective for hypertensive patients with DHF by improving the quality of life, echo-derived myocardial function, and reducing ventricular mechanical stretch through lessening the degree of LV hypertrophy and myocardial fibrosis.

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.
40

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 4

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • well-controlled hypertensive patients with diastolic HF defined as the presence of diastolic dysfunction, normal LVEF (> 50 %), and exertional dyspnea (≧ New York Heart Association functional class II) or other HF signs/symptoms fulfilled with the Framingham criteria despite optimal pharmacological therapy

Exclusion Criteria:

  • secondary hypertension
  • restrictive, constrictive or hypertrophic cardiomyopathy
  • more than moderate (mitral or tricuspid regurgitant jet area/atrial area more than 20%; aortic regurgitant jet to the tip of the mitral valve leaflets) valvular heart diseases
  • chronic atrial fibrillation
  • usage of aldosterone antagonist within 3 months
  • chronic pulmonary disease
  • myocardial infarction within 3 months or active ischemia needing revascularization
  • LVEF less than 50% by echocardiography
  • renal failure (serum creatinine concentration more than 2.0 mg/dL).

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: Single Group Assignment
  • Masking: Single

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: aldactone
aldactone 25 mg for 6 months
Drug: aldactone
aldactone 25 mg for 6 months
No Intervention: without aldactone

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
peak myocardial velocity (Sm) during the ejection phase over the 6-basal segments
Time Frame: 6 months
6 months

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
Time Frame
pro-brain natriuretic peptide (proBNP)
Time Frame: 6 months
6 months
matrix metalloproteinase-2 (MMP-2)
Time Frame: 6 months
6 months
matrix metalloproteinase-9 (MMP-9), etc.
Time Frame: 6 months
6 months
carboxy-terminal telopeptide of collagen I(ICTP)
Time Frame: 6 months
6 months
procollagen type III amino-terminal propeptide (PIIINP)
Time Frame: 6 months
6 months
soluble ST2 receptor (sST2)
Time Frame: 6 months
6 months

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.
National Taiwan University Hospital

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.
  • Principal Investigator: Wang Yi Chih, MD, PhD, NTUH

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, 2010

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.
December 1, 2010

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.
December 1, 2011

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 4, 2013

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 12, 2013

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 17, 2013

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.
September 17, 2013

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.
September 12, 2013

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.
September 1, 2013

More Information

Terms related to this study

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.
  • 200912097M

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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