Idiopathic Dilated CardiomyopathyPhase 4BORGNCT01798992
Effect of Beta-blockers on Structural Remodeling and Gene Expression in the Failing Human Heart
A Phase 4 study testing Carvedilol, Metoprolol succinate and Metoprolol succinate + doxazosin in people with Idiopathic Dilated Cardiomyopathy, run by University of Colorado, Denver at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Idiopathic Dilated Cardiomyopathy
- What is being tested?
- Carvedilol, Metoprolol succinate and Metoprolol succinate + doxazosin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2000to Mar 2009
- 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
- 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
Who cannot join
- 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:
- Calcium channel blockers
- Theophylline
- Tricyclic antidepressants
Show all 22Show fewer
- Monoamine oxidase inhibitors
- β-agonists
- β-adrenergic blocking agent (oral)
- Any investigational cardiovascular medication or involvement in another investigational trial
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Colorado Hospital
Denver, Colorado, 80220
University of Utah Medical Center
Salt Lake City, Utah, 84132
About this study
Official title: Beta-blocker Effect on Structural Remodeling and Gene Expression in the Failing Human Heart
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:
- Aim: Determine the changes in gene expression associated with changes in intrinsic systolic function and with functional decompensation in the intact, failing human heart.
- Hypothesis: Changes in the expression of select genes precede or accompany changes in left ventricular systolic function in humans with idiopathic dilated cardiomyopathy (IDC).
- Aim: Identify signaling mechanisms responsible for alterations in expression of key genes involved in mediation of ventricular hypertrophy or contractile dysfunction.
- Hypothesis: Myocardial-failure-associated regulation of select messenger ribonucleic acids and proteins are related to left ventricular wall stress and neurohormonal signaling.
- Aim: In the relationship between contractile dysfunction and dilatation/remodeling, determine the relationship between contractile dysfunction and structural remodeling.
- Hypothesis: the contractile dysfunction is primary and structural remodeling secondary.
- Conditions
- Idiopathic Dilated Cardiomyopathy
- Being tested
- Carvedilol, Metoprolol succinate, Metoprolol succinate + doxazosin
- Keywords
- ejection fraction, beta-blocker, carvedilol, metoprolol, myocardial gene expression, human heart, ventricular remodeling, wall stress, adrenergic signaling, myosin heavy chain
- Medical subject headings
- Cardiomyopathy, Dilated, Ventricular Remodeling
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarvedilolDrug
Also called Coreg
Metoprolol succinateDrug
Also called Toprol XL
Metoprolol succinate + doxazosinDrug
Also called Toprol XL, Cardura, Carduran
| Study group | Role | What they receive |
|---|---|---|
| Non-failing control | No intervention | Patients with normal ejection fraction who underwent a single myocardial biopsy and received no β-blocker therapy |
| Metoprolol succinate | Active comparator | Idiopathic dilated cardiomyopathy patients randomized to metoprolol succinate titrated to a goal of 200 mg by mouth daily for 18 months Receives: Drug: Metoprolol succinate |
| Metoprolol succinate + doxazosin | Active comparator | 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 Receives: Drug: Metoprolol succinate + doxazosin |
| Carvedilol | Active comparator | Idiopathic dilated cardiomyopathy patients who were randomized to receive carvedilol titrated to a goal of 25 mg by mouth twice daily for 18 months Receives: Drug: Carvedilol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement in Left Ventricular Ejection Fraction (LVEF) at 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.
Measured: 12 months
Secondary outcomes (2)
Improvement in LVEF at 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.
Measured: 3 months
Composite of All-cause Mortality, Need for Heart Transplant or Need for Ventricular Assist Device.
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.
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2013 (estimated)
- Study startSep 2000
- Primary completionMar 2009
- Study completionMar 2009
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 (2)Papers the sponsor has linked to this study.
- Other trials for Idiopathic Dilated CardiomyopathyStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michael R Bristow, MD PhD, Principal investigator, University of Colorado School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01798992
- Sponsor's protocol ID
- 00-0242
- Other IDs
- 2R01HL048013
- Acronym
- BORG
- Status last verified
- Nov 2023
- First submitted
- 22 Feb 2013
- Last updated
- 29 Nov 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Sucharov CC, Kao DP, Port JD, Karimpour-Fard A, Quaife RA, Minobe W, Nunley K, Lowes BD, Gilbert EM, Bristow MR. Myocardial microRNAs associated with reverse remodeling in human heart failure. JCI Insight. 2017 Jan 26;2(2):e89169. doi: 10.1172/jci.insight.89169.
PubMed 28138556Kao DP, Lowes BD, Gilbert EM, Minobe W, Epperson LE, Meyer LK, Ferguson DA, Volkman AK, Zolty R, Borg CD, Quaife RA, Bristow MR. Therapeutic Molecular Phenotype of beta-Blocker-Associated Reverse-Remodeling in Nonischemic Dilated Cardiomyopathy. Circ Cardiovasc Genet. 2015 Apr;8(2):270-83. doi: 10.1161/CIRCGENETICS.114.000767. Epub 2015 Jan 30.
PubMed 25637602
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Beta-blocker Effect on Structural Remodeling and Gene Expression in the Failing Human Heart
- ClinicalTrials.gov ID
- NCT01798992
- Acronym / sponsor ID
- BORG / 00-0242
- Conditions
- Idiopathic Dilated Cardiomyopathy
- Keywords
- ejection fraction, beta-blocker, carvedilol, metoprolol, myocardial gene expression, human heart, ventricular remodeling, wall stress
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), GlaxoSmithKline, AstraZeneca
- Study start
- Sep 2000
- Primary completion
- Mar 2009 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 26 Feb 2013 (estimated)
- Results
- Posted 20 Feb 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Aim: Determine the changes in gene expression associated with changes in intrinsic systolic function and with functional decompensation in the intact, failing human heart.
- Hypothesis: Changes in the expression of select genes precede or accompany changes in left ventricular systolic function in humans with idiopathic dilated cardiomyopathy (IDC).
- Aim: Identify signaling mechanisms responsible for alterations in expression of key genes involved in mediation of ventricular hypertrophy or contractile dysfunction.
- Hypothesis: Myocardial-failure-associated regulation of select messenger ribonucleic acids and proteins are related to left ventricular wall stress and neurohormonal signaling.
- Aim: In the relationship between contractile dysfunction and dilatation/remodeling, determine the relationship between contractile dysfunction and structural remodeling.
- Hypothesis: the contractile dysfunction is primary and structural remodeling secondary.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Non-failing control | No intervention | –Patients with normal ejection fraction who underwent a single myocardial biopsy and received no β-blocker therapy |
| Metoprolol succinate | Active comparator | Drug: Metoprolol succinateIdiopathic dilated cardiomyopathy patients randomized to metoprolol succinate titrated to a goal of 200 mg by mouth daily for 18 months |
| Metoprolol succinate + doxazosin | Active comparator | Drug: Metoprolol succinate + doxazosinIdiopathic 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 |
| Carvedilol | Active comparator | Drug: CarvedilolIdiopathic dilated cardiomyopathy patients who were randomized to receive carvedilol titrated to a goal of 25 mg by mouth twice daily for 18 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (22 listed)
- 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:
- Patient has a contraindication to β-blockade (eg asthma)
- Patient has another life-threatening disease with life expectancy < 2 years due to other illness
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 |
|---|---|---|
| CarvedilolAlso: Coreg | Drug | Carvedilol |
| Metoprolol succinateAlso: Toprol XL | Drug | Metoprolol succinate |
| Metoprolol succinate + doxazosinAlso: Toprol XL, Cardura, Carduran | Drug | Metoprolol succinate + doxazosin |
Primary outcome
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.
2 secondary outcomes
Improvement in LVEF at 3 Months
Time frame: 3 months
Composite of All-cause Mortality, Need for Heart Transplant or Need for Ventricular Assist Device.
Time frame: 18 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28138556Sucharov CC, Kao DP, Port JD, Karimpour-Fard A, Quaife RA, Minobe W, Nunley K, Lowes BD, Gilbert EM, Bristow MR. Myocardial microRNAs associated with reverse remodeling in human heart failure. JCI Insight. 2017 Jan 26;2(2):e89169. doi: 10.1172/jci.insight.89169.
- Derived from this study: PubMed 25637602Kao DP, Lowes BD, Gilbert EM, Minobe W, Epperson LE, Meyer LK, Ferguson DA, Volkman AK, Zolty R, Borg CD, Quaife RA, Bristow MR. Therapeutic Molecular Phenotype of beta-Blocker-Associated Reverse-Remodeling in Nonischemic Dilated Cardiomyopathy. Circ Cardiovasc Genet. 2015 Apr;8(2):270-83. doi: 10.1161/CIRCGENETICS.114.000767. Epub 2015 Jan 30.
Related trials for Idiopathic Dilated Cardiomyopathy
RecruitingPhase 1/2
An AAV Gene Therapy Trial of AFTX-201 in Adults With BAG3-Associated Dilated Cardiomyopathy (DCM)
Dilated Cardiomyopathy (DCM), BAG3 Mutation Associated Dilated Cardiomyopathy
Active, not recruiting
Microvascular Dysfunction Assessment to Predict Left Ventricular Reverse Remodeling
Heart Failure, Left Ventricular Dysfunction
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
RecruitingPhase 1/2
Endocardial Delivery for Myocardial Regeneration Using Allogeneic iPSC-derived Cardiomyocyte Spheroids for HF With Systolic Dysfunction (EMERALD Study)
Heart Failure, Ischemic Heart Failure
RecruitingObservational study
Observational Study of Natural History of BAG3 Gene Mutation-Associated Dilated Cardiomyopathy in Chinese Adults
Dilated Cardiomyopathy
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.
Michael R Bristow, MD PhD principal investigator
University of Colorado School of Medicine
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Carvedilol, Metoprolol succinate and Metoprolol succinate + doxazosin in people with Idiopathic Dilated Cardiomyopathy, run by University of Colorado, Denver at 2 sites 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 7 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 29 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 20 Feb 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 Left Ventricular Ejection Fraction (LVEF) at 12 Months (time frame: 12 months). 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 NCT01798992, which also lists 2 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 29 Nov 2023.