DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more

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

Information source: University of Colorado, Denver
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Idiopathic Dilated Cardiomyopathy

Intervention: Carvedilol (Drug); Metoprolol succinate (Drug); Metoprolol succinate + doxazosin (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: University of Colorado, Denver

Official(s) and/or principal investigator(s):
Michael R Bristow, MD PhD, Principal Investigator, Affiliation: University of Colorado School of Medicine


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.

Clinical Details

Official title: Beta-blocker Effect on Structural Remodeling and Gene Expression in the Failing Human Heart

Study design: Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Primary outcome: Improvement in left ventricular ejection fraction (LVEF) at 12 months

Secondary outcome:

Improvement in LVEF at 3 months

Composite of all-cause mortality, need for heart transplant or need for ventricular assist device


Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.


Inclusion Criteria:

- Idiopathic dilated cardiomyopathy with New York Heart Association Class II-IV


- 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


- 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


- Patient is unable to go magnetic resonance imaging procedures

- Patient has demonstrated non-compliance with previous medical regimens

Locations and Contacts

University of Colorado Hospital, Denver, Colorado 80220, United States

University of Utah Medical Center, Salt Lake City, Utah 84132, United States

Additional Information

Starting date: September 2000
Last updated: May 1, 2013

Page last updated: August 23, 2015

-- advertisement -- The American Red Cross
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017