Clinical and Therapeutic Implications of Fibrosis in Hypertrophic Cardiomyopathy - Full Text View

Sponsor:	Tufts Medical Center
Information provided by:	Tufts Medical Center
ClinicalTrials.gov Identifier:	NCT00879060

Purpose

Hypertrophic Cardiomyopathy (HCM) is the most common genetic cardiomyopathy and remains the leading cause of sudden cardiac death in young people and an important cause of heart failure symptoms and death at any age. In HCM, pathological remodeling of the left ventricle involving myocardial fibrosis is likely a major contributor to cardiac dysfunction and also a nidus for the generation of ventricular arrhythmias. Serum markers of collagen turnover have been shown to reliably reflect the magnitude of myocardial fibrosis in a variety of cardiovascular diseases. In addition, aldosterone antagonist drugs have been shown to decrease fibrous tissue formation in the myocardium in certain pathologic cardiovascular states in which aldosterone production is increased. In HCM, aldosterone production is up-regulated and has been implicated in the formation of myocardial fibrosis.

Therefore, the specific aims of this proposal are to:

assess serum markers of collagen turnover at baseline and correlate these findings with a variety of clinical and morphologic disease parameters
examine the effects of a 12-month treatment with the aldosterone antagonist spironolactone on magnitude of fibrosis as measured by serum markers of collagen turnover as well as changes in clinical and morphologic disease parameters.

The results of this proposal will offer important insights into the clinical significance of myocardial fibrosis in this primary genetic cardiomyopathy. The demonstration that spironolactone decreases fibrosis and improves clinical course would provide the rational for a larger multicenter clinical trial evaluating this novel therapy for improving clinical outcome in patients with HCM.

Condition	Intervention	Phase
Myocardial Fibrosis Hypertrophic Cardiomyopathy	Drug: spironolactone	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Clinical and Therapeutic Implications of Fibrosis in Hypertrophic

Resource links provided by NLM:

MedlinePlus related topics: Cardiomyopathy

Drug Information available for: Spironolactone

U.S. FDA Resources

Further study details as provided by Tufts Medical Center:

Primary Outcome Measures:

changes in serum markers of collagen turnover [ Time Frame: one year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

measures of diastolic function by echocardiography [ Time Frame: one year ] [ Designated as safety issue: No ]
cardiac mass and fibrosis by cardiac magnetic resonance imaging (CMR) [ Time Frame: one year ] [ Designated as safety issue: No ]
exercise tolerance by exercise VO2max and Holter [ Time Frame: one year ] [ Designated as safety issue: No ]

Estimated Enrollment:	95
Study Start Date:	November 2007
Estimated Study Completion Date:	November 2012
Estimated Primary Completion Date:	November 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
spironolactone: Experimental	Drug: spironolactone spironolactone 50mg daily

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Hypertrophic cardiomyopathy
Able to swallow pills
No prior septal reduction therapy
Negative serum or hCG pregnancy test

Exclusion Criteria:

Unable or unwilling to perform treadmill cardiopulmonary exercise test
Prior surgical myectomy or alcohol septal ablation
Known or suspected infiltrative or glycogen storage disease
Significant coronary artery disease, defined as atherosclerotic coronary artery narrowing >70% of the luminal diameter by coronary angiography
Severe obstructive pulmonary disease, defined as forced expiratory volume in 1 second (FEV1) <50% of predicted.
Prior intolerance or adverse reaction to aldosterone receptor antagonist.
History of hyper or hypoaldosteronism
Baseline serum potassium >5.0 mmol/L.
Calculated creatinine clearance <30 ml/min using Cockcroft-Gault formula.
Pregnant or breast feeding
Poorly controlled systemic hypertension, defined as systolic blood pressure ≥150 mmHg or diastolic pressure ≥100 mmHg, during 2 clinic visits.
Known conditions associated with elevated serum concentrations of PIIINP (e.g., chronic liver disease, diabetes mellitus, tumors, pulmonary fibrosis, bone and rheumatoid diseases, extensive wounds) or PINP (e.g., alcoholic liver disease, metabolic bone disease, thyroid disorders), including recent trauma (≤2 weeks) or surgery (≤6 months)
Taking drugs known to directly influence collagen metabolism including, amiodorone, ACE or angiotensin II inhibitors, aldosterone antagonists, statins, glucocorticoids and estrogens
Patients with ICDs/pacemakers will be recruited in the study, but will be excluded from the CMR component.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00879060

Contacts

Contact: Martin S Maron, MD	617 636-8066	mmaron@tuftsmedicalcenter.org
Contact: James E Udelson, MD	6176368066	judelson@tuftsmedicalcenter.org

Locations

United States, Massachusetts
Tufts Medical Center	Recruiting
Boston, Massachusetts, United States, 02111
Contact: Martin S Maron, MD 617-636-8066 mmaron@tuftsmedicalcenter.org
Contact: James E Udelson, MD 6176368066 judelson@tuftsmedicalcenter.org
Principal Investigator: Martin S Maron, MD

Sponsors and Collaborators

Tufts Medical Center

More Information

No publications provided

Responsible Party:	Tufts Medical Center ( Martin Maron )
Study ID Numbers:	K23 HL086745-01A1
Study First Received:	April 8, 2009
Last Updated:	April 8, 2009
ClinicalTrials.gov Identifier:	NCT00879060 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Tufts Medical Center:

Fibrosis
Hypertrophic cardiomyopathy
MRI
To evaluate the efficacy of spironolactone in decreasing myocardial fibrosis in Hypertrophic cardiomyopathy

Additional relevant MeSH terms:

Pathological Conditions, Anatomical
Heart Diseases
Fibrosis
Hormone Antagonists
Physiological Effects of Drugs
Diuretics
Hormones, Hormone Substitutes, and Hormone Antagonists
Cardiovascular Agents
Cardiomyopathies
Pharmacologic Actions
Heart Valve Diseases

Spironolactone
Hypertrophy
Aortic Stenosis, Subvalvular
Pathologic Processes
Aldosterone Antagonists
Natriuretic Agents
Therapeutic Uses
Cardiomyopathy, Hypertrophic
Cardiovascular Diseases
Aortic Valve Stenosis

ClinicalTrials.gov processed this record on February 08, 2010