Clinical and Therapeutic Implications of Fibrosis in Hypertrophic Cardiomyopathy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00879060
Recruitment Status : Unknown
Verified April 2009 by Tufts Medical Center.
Recruitment status was:  Recruiting
First Posted : April 9, 2009
Last Update Posted : April 9, 2009
Information provided by:
Tufts Medical Center

Brief Summary:

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:

  1. assess serum markers of collagen turnover at baseline and correlate these findings with a variety of clinical and morphologic disease parameters
  2. 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 or disease Intervention/treatment Phase
Myocardial Fibrosis Hypertrophic Cardiomyopathy Drug: spironolactone Phase 4

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 95 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Clinical and Therapeutic Implications of Fibrosis in Hypertrophic
Study Start Date : November 2007
Estimated Primary Completion Date : November 2011
Estimated Study Completion Date : November 2012

Arm Intervention/treatment
Experimental: spironolactone Drug: spironolactone
spironolactone 50mg daily

Primary Outcome Measures :
  1. changes in serum markers of collagen turnover [ Time Frame: one year ]

Secondary Outcome Measures :
  1. measures of diastolic function by echocardiography [ Time Frame: one year ]
  2. cardiac mass and fibrosis by cardiac magnetic resonance imaging (CMR) [ Time Frame: one year ]
  3. exercise tolerance by exercise VO2max and Holter [ Time Frame: one year ]

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  1. Hypertrophic cardiomyopathy
  2. Able to swallow pills
  3. No prior septal reduction therapy
  4. Negative serum or hCG pregnancy test

Exclusion Criteria:

  1. Unable or unwilling to perform treadmill cardiopulmonary exercise test
  2. Prior surgical myectomy or alcohol septal ablation
  3. Known or suspected infiltrative or glycogen storage disease
  4. Significant coronary artery disease, defined as atherosclerotic coronary artery narrowing >70% of the luminal diameter by coronary angiography
  5. Severe obstructive pulmonary disease, defined as forced expiratory volume in 1 second (FEV1) <50% of predicted.
  6. Prior intolerance or adverse reaction to aldosterone receptor antagonist.
  7. History of hyper or hypoaldosteronism
  8. Baseline serum potassium >5.0 mmol/L.
  9. Calculated creatinine clearance <30 ml/min using Cockcroft-Gault formula.
  10. Pregnant or breast feeding
  11. Poorly controlled systemic hypertension, defined as systolic blood pressure ≥150 mmHg or diastolic pressure ≥100 mmHg, during 2 clinic visits.
  12. 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)
  13. Taking drugs known to directly influence collagen metabolism including, amiodorone, ACE or angiotensin II inhibitors, aldosterone antagonists, statins, glucocorticoids and estrogens
  14. Patients with ICDs/pacemakers will be recruited in the study, but will be excluded from the CMR component.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00879060

Contact: Martin S Maron, MD 617 636-8066
Contact: James E Udelson, MD 6176368066

United States, Massachusetts
Tufts Medical Center Recruiting
Boston, Massachusetts, United States, 02111
Contact: Martin S Maron, MD    617-636-8066   
Contact: James E Udelson, MD    6176368066   
Principal Investigator: Martin S Maron, MD         
Sponsors and Collaborators
Tufts Medical Center

Responsible Party: Martin Maron, Tufts Medical Center Identifier: NCT00879060     History of Changes
Other Study ID Numbers: K23HL086745-01A1 ( U.S. NIH Grant/Contract )
First Posted: April 9, 2009    Key Record Dates
Last Update Posted: April 9, 2009
Last Verified: April 2009

Keywords provided by Tufts Medical Center:
Hypertrophic cardiomyopathy
To evaluate the efficacy of spironolactone in decreasing myocardial fibrosis in Hypertrophic cardiomyopathy

Additional relevant MeSH terms:
Cardiomyopathy, Hypertrophic
Pathologic Processes
Heart Diseases
Cardiovascular Diseases
Pathological Conditions, Anatomical
Aortic Stenosis, Subvalvular
Aortic Valve Stenosis
Heart Valve Diseases
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Diuretics, Potassium Sparing
Natriuretic Agents