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Trial record 35 of 163 for:    Idiopathic Dilated Cardiomyopathy

Effect of Beta-blockers on Structural Remodeling and Gene Expression in the Failing Human Heart (BORG)

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ClinicalTrials.gov Identifier: NCT01798992
Recruitment Status : Completed
First Posted : February 26, 2013
Results First Posted : February 20, 2017
Last Update Posted : August 14, 2018
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
GlaxoSmithKline
AstraZeneca
Information provided by (Responsible Party):
University of Colorado, Denver

Tracking Information
First Submitted Date  ICMJE February 22, 2013
First Posted Date  ICMJE February 26, 2013
Results First Submitted Date  ICMJE June 6, 2016
Results First Posted Date  ICMJE February 20, 2017
Last Update Posted Date August 14, 2018
Study Start Date  ICMJE September 2000
Actual Primary Completion Date March 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 27, 2016)
Improvement in Left Ventricular Ejection Fraction (LVEF) at 12 Months [ Time Frame: 12 months ]
The primary clinical outcome will be LVEF response at 12 months defined as an improvement in LVEF of ≥ 8% at 12 months or if not available, ≥5% at 3 months in the absence of an adverse clinical outcome. Data are not presented for non-failing controls, who only went baseline evaluation and did not undergo treatment, given that they did not have heart failure.
Original Primary Outcome Measures  ICMJE
 (submitted: February 22, 2013)
Improvement in Left Ventricular Ejection Fraction (LVEF) at 12 Months [ Time Frame: 12 months ]
The primary clinical outcome will be LVEF response at 12 months defined as an improvement in LVEF of ≥ 8% at 12 months or if not available, ≥5% at 3 months in the absence of an adverse clinical outcome.
Change History Complete list of historical versions of study NCT01798992 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 27, 2016)
  • Improvement in LVEF at 3 Months [ Time Frame: 3 months ]
    A secondary outcome will be LVEF response at 3 months, defined as an improvement of ≥ 5% Data are not presented for non-failing controls, who only went baseline evaluation and did not undergo treatment, given that they did not have heart failure.
  • Composite of All-cause Mortality, Need for Heart Transplant or Need for Ventricular Assist Device. [ Time Frame: 18 months ]
    Clinical status at 18 months will be assessed at time of study completion, specifically for the composite outcome of all-cause mortality, need for heart transplant, or need for ventricular assist device. Outcomes are not presented for non-failing controls, who only went baseline evaluation and did not undergo treatment, given that they did not have heart failure.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 22, 2013)
  • Improvement in LVEF at 3 Months [ Time Frame: 3 months ]
    A secondary outcome will be LVEF response at 3 months, defined as an improvement of ≥ 5%
  • Composite of all-cause mortality, need for heart transplant or need for ventricular assist device [ Time Frame: 18 months ]
    Clinical status at 18 months will be assessed at time of study completion, specifically for the composite outcome of all-cause mortality, need for heart transplant, or need for ventricular assist device.
Current Other Pre-specified Outcome Measures
 (submitted: December 27, 2016)
  • Change in Myocardial Gene Expression at 3 Months [ Time Frame: 3 months ]
    Changes in myocardial mRNA expression at 3 months compared to baseline using targeted quantitative polymerase chain reaction and genome wide microarray assays. Due to the large number of results genes interrogated (~ 20,000 genes), these results will instead be uploaded to the Gene Expression Omnibus.
  • Change in Myocardial Gene Expression at 12 Months [ Time Frame: 12 months ]
    Changes in myocardial mRNA expression at 12 months compared to baseline using targeted quantitative polymerase chain reaction and Affymetrix genome-wide microarray assays. Data are not presented for non-failing controls, who only went baseline evaluation and did not undergo treatment, given that they did not have heart failure.
  • Change in Myocardial microRNA Expression at 3 Months [ Time Frame: 3 months ]
    Changes in myocardial microRNA expression at 3 months compared to baseline using an Affymetrix microRNA microarray assay. Data are not presented for non-failing controls, who only went baseline evaluation and did not undergo treatment, given that they did not have heart failure.
  • Change in Myocardial microRNA Expression at 12 Months [ Time Frame: 12 months ]
    Changes in myocardial microRNA expression at 12 months compared to baseline using an Affymetrix microRNA microarray assay. Data are not presented for non-failing controls, who only went baseline evaluation and did not undergo treatment, given that they did not have heart failure.
Original Other Pre-specified Outcome Measures
 (submitted: February 22, 2013)
  • Change in Myocardial Gene Expression at 3 Months [ Time Frame: 3 months ]
    Changes in myocardial mRNA expression at 3 months compared to baseline using targeted quantitative polymerase chain reaction and genome wide microarray assays
  • Change in Myocardial Gene Expression at 12 Months [ Time Frame: 12 months ]
    Changes in myocardial mRNA expression at 12 months compared to baseline using targeted quantitative polymerase chain reaction and Affymetrix genome-wide microarray assays
  • Change in Myocardial microRNA Expression at 3 Months [ Time Frame: 3 months ]
    Changes in myocardial microRNA expression at 3 months compared to baseline using an Affymetrix microRNA microarray assay
  • Change in Myocardial microRNA Expression at 12 Months [ Time Frame: 12 months ]
    Changes in myocardial microRNA expression at 12 months compared to baseline using an Affymetrix microRNA microarray assay
 
Descriptive Information
Brief Title  ICMJE Effect of Beta-blockers on Structural Remodeling and Gene Expression in the Failing Human Heart
Official Title  ICMJE Beta-blocker Effect on Structural Remodeling and Gene Expression in the Failing Human Heart
Brief Summary

The primary goal of the study is to measure in the intact human heart, the alterations in gene expression over time that are associated with reverse remodeling in response to β-blockade. The second goal is to investigate the signaling mechanisms which in turn are responsible for these changes in gene expression, and the third goal is to determine the relationship between intrinsic systolic dysfunction and remodeling of the left ventricle. This will be accomplished by measuring ventricular size, function, and gene expression in myocardial tissue samples obtained by percutaneous biopsy prior to initiation of β-blockade and at 3 and 12 months after start of therapy. The specific Aims and Hypotheses to be tested are:

  1. Aim: Determine the changes in gene expression associated with changes in intrinsic systolic function and with functional decompensation in the intact, failing human heart.

    a. Hypothesis: Changes in the expression of select genes precede or accompany changes in left ventricular systolic function in humans with idiopathic dilated cardiomyopathy (IDC).

  2. Aim: Identify signaling mechanisms responsible for alterations in expression of key genes involved in mediation of ventricular hypertrophy or contractile dysfunction.

    a. Hypothesis: Myocardial-failure-associated regulation of select messenger ribonucleic acids and proteins are related to left ventricular wall stress and neurohormonal signaling.

  3. Aim: In the relationship between contractile dysfunction and dilatation/remodeling, determine the relationship between contractile dysfunction and structural remodeling.

    b. Hypothesis: the contractile dysfunction is primary and structural remodeling secondary.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Idiopathic Dilated Cardiomyopathy
Intervention  ICMJE
  • Drug: Carvedilol
    Other Name: Coreg
  • Drug: Metoprolol succinate
    Other Name: Toprol XL
  • Drug: Metoprolol succinate + doxazosin
    Other Names:
    • Toprol XL
    • Cardura
    • Carduran
Study Arms  ICMJE
  • No Intervention: Non-failing control
    Patients with normal ejection fraction who underwent a single myocardial biopsy and received no β-blocker therapy
  • Active Comparator: Metoprolol succinate
    Idiopathic dilated cardiomyopathy patients randomized to metoprolol succinate titrated to a goal of 200 mg by mouth daily for 18 months
    Intervention: Drug: Metoprolol succinate
  • Active Comparator: Metoprolol succinate + doxazosin
    Idiopathic dilated cardiomyopathy patients who were randomized to receive metoprolol succinate and doxazosin titrated to a goal of 200 mg and 8 mg by mouth daily for 18 months
    Intervention: Drug: Metoprolol succinate + doxazosin
  • Active Comparator: Carvedilol
    Idiopathic dilated cardiomyopathy patients who were randomized to receive carvedilol titrated to a goal of 25 mg by mouth twice daily for 18 months
    Intervention: Drug: Carvedilol
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 27, 2016)
56
Original Actual Enrollment  ICMJE
 (submitted: February 22, 2013)
51
Actual Study Completion Date  ICMJE March 2009
Actual Primary Completion Date March 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Idiopathic dilated cardiomyopathy with New York Heart Association Class II-IV symptoms
  • No evidence of coronary artery disease by angiography within 2 years of randomization
  • If female, patient is (a) surgically sterile or (b) practices an accepted method of birth control and has negative serum pregnancy test
  • Patient has been on other conventional cardiac heart failure(CHF) therapy at least 3 weeks prior to baseline assessments (includes angiotensin converting enzyme inhibitors, digoxin, diuretics, and/or vasodilators)
  • Patient has left ventricular ejection fraction < 40% by radionuclide ventriculography within 60 days of randomization
  • Patient must demonstrate mental and physical ability and willingness to follow all study-specific instructions
  • Patient must voluntarily sign Institutional Review Board (IRB)-approved informed consent form prior to any study-specific procedure

Exclusion Criteria:

  • Patient has heart failure due to or associated with uncorrected primary valvular disease, uncorrected thyroid disease, obstructive/hypertrophic cardiomyopathy, pericardial disease, amyloidosis, active myocarditis, or malfunctioning artificial heart valve.
  • Patient is actively on heart transplant list or anticipated to be within 6 months of randomization
  • Patient is receiving any of the following medicines:

    1. Calcium channel blockers
    2. Theophylline
    3. Tricyclic antidepressants
    4. Monoamine oxidase inhibitors
    5. β-agonists
    6. β-adrenergic blocking agent (oral)
    7. Any investigational cardiovascular medication or involvement in another investigational trial
    8. Flecainide, encainide, propafenone, sotalol, disopyramide, or amiodarone
  • Patient has a contraindication to β-blockade (eg asthma)
  • Patient has another life-threatening disease with life expectancy < 2 years due to other illness
  • Patient has active hepatic, renal, hematologic, gastrointestinal, immunologic, endocrine, metabolic, or central nervous system disease which may adversely affect the safety and efficacy of the study drug or life span of the patient
  • Unstable decompensated heart failure (evidence of hypoperfusion, acute pulmonary edema, or hypotension with SBP < 80 mm Hg)
  • Patient is actively abusing ethanol or illicit drugs within 3 months of randomization
  • Patient has an automatic implantable cardiac defibrillator that has fired within 3 months of randomization
  • Patient has an asymptomatic waking, resting heart rate < 50 bpm or symptomatic bradycardia < 60 bpm.
  • Patient has uncontrolled insulin-dependent diabetes mellitus with a history of frequent hypoglycemia episodes
  • Patient has a high degree atrioventricular block (Mobitz Type II or complete heart block)
  • Patient is unable to tolerate magnetic resonance imaging procedures
  • Patient has demonstrated non-compliance with previous medical regimens
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01798992
Other Study ID Numbers  ICMJE 00-0242
2R01HL048013 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Colorado, Denver
Study Sponsor  ICMJE University of Colorado, Denver
Collaborators  ICMJE
  • National Heart, Lung, and Blood Institute (NHLBI)
  • GlaxoSmithKline
  • AstraZeneca
Investigators  ICMJE
Principal Investigator: Michael R Bristow, MD PhD University of Colorado School of Medicine
PRS Account University of Colorado, Denver
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP