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Clinical and Therapeutic Implications of Fibrosis in Hypertrophic Cardiomyopathy

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2009 by Tufts Medical Center.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Tufts Medical Center
ClinicalTrials.gov Identifier:
NCT00879060
First received: April 8, 2009
Last updated: NA
Last verified: April 2009
History: No changes posted
  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:

  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 Intervention Phase
Myocardial Fibrosis
Hypertrophic Cardiomyopathy
 Drug: spironolactone
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Clinical and Therapeutic Implications of Fibrosis in Hypertrophic

Resource links provided by NLM:

MedlinePlus related topics: Cardiomyopathy
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
Experimental: spironolactone 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:

  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.
  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: Martin Maron, Tufts Medical Center
ClinicalTrials.gov Identifier: NCT00879060     History of Changes
Other Study ID Numbers: K23 HL086745-01A1
Study First Received: April 8, 2009
Last Updated: April 8, 2009
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:
Cardiomyopathy, Hypertrophic
Fibrosis
Hypertrophy
Cardiomyopathies
Heart Diseases
Cardiovascular Diseases
Aortic Stenosis, Subvalvular
Aortic Valve Stenosis
Heart Valve Diseases
Pathologic Processes
Pathological Conditions, Anatomical
 Spironolactone
Aldosterone Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Diuretics
Natriuretic Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on June 18, 2013