Treatment of Preclinical Hypertrophic Cardiomyopathy With Diltiazem - Full Text View

Sponsor:	Brigham and Women's Hospital
Collaborators:	National Heart, Lung, and Blood Institute (NHLBI) Children's Hospital Boston
Information provided by:	Brigham and Women's Hospital
ClinicalTrials.gov Identifier:	NCT00319982

Purpose

This is a pilot clinical study to assess whether the administration of diltiazem may be able to decrease the development or progression of hypertrophic cardiomyopathy (HCM). Diltiazem is a commonly used medication for the treatment of high blood pressure and studies on animals with HCM suggest that diltiazem decreases disease development. This study specifically targets individuals in the "prehypertrophic" phase of HCM-- those with documented sarcomere gene mutations without echocardiographic or EKG evidence of LVH.

The hypothesis of this study is that starting diltiazem administration early in life (in the prehypertrophic phase) will decrease the progression of HCM in individuals with sarcomere gene mutations. This will be assessed by looking at an improvement in the heart's ability to relax using echocardiography.

Condition	Intervention	Phase
Hypertrophic Cardiomyopathy	Drug: Diltiazem Drug: Placebo	Phase II Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Treatment of Preclinical Hypertrophic Cardiomyopathy With Diltiazem

Resource links provided by NLM:

MedlinePlus related topics: Cardiomyopathy

Drug Information available for: Verapamil Diltiazem hydrochloride Dexverapamil Diltiazem Diltiazem malate Verapamil hydrochloride

U.S. FDA Resources

Further study details as provided by Brigham and Women's Hospital:

Primary Outcome Measures:

Improvement, stability of, or decrease in the decline of diastolic function as reflected by the averaged early myocardial relaxation (Ea) velocity compared to baseline [ Time Frame: 6, and 18 months, annually and at study end ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Improvement of Ea velocities [ Time Frame: 6, and 18 months, annually and at study end ] [ Designated as safety issue: No ]
Stability of Ea velocities [ Time Frame: 6, and 18 months, annually and at study end ] [ Designated as safety issue: No ]
Attenuation of the decline of Ea velocities [ Time Frame: 6, and 18 months, annually and at study end ] [ Designated as safety issue: No ]
Delayed or Attenuated development of left ventricular hypertrophy [ Time Frame: 6, and 18 months, annually and at study end ] [ Designated as safety issue: No ]
Improvement in, stability of, or attenuation of increase in serum biomarkers (ANP, BNP, and markers of mechanical stress and collagen turnover) [ Time Frame: Annual visits ] [ Designated as safety issue: No ]
Improvement in, stability of or attenuation of increase in MRI evidence of myocardial fibrosis [ Time Frame: Study end ] [ Designated as safety issue: No ]
Safety: no excess of all cause death, CV death (including sudden death), heart failure requiring medication or hospitalization [ Time Frame: Biannually ] [ Designated as safety issue: Yes ]
Tolerability: no excess need to reduce or withdraw study medication [ Time Frame: Biannually ] [ Designated as safety issue: No ]

Estimated Enrollment:	50
Study Start Date:	January 2006
Estimated Study Completion Date:	December 2013
Estimated Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: I	Drug: Diltiazem Titrated to a target dose of 360 mg daily (sustained release formulation) for the duration of the study period
Placebo Comparator: II Placebo Comparator	Drug: Placebo Placebo comparator (double-blind allocation of study medication)

Show Detailed Description

Eligibility

Ages Eligible for Study:	5 Years to 39 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Preclinical HCM (identified sarcomere mutation with no clinical evidence of left ventricular hypertrophy)
Able to provide informed consent (or parental consent)

Exclusion Criteria:

Contraindication to diltiazem administration
Impaired hepatic or renal function
Age < 5 years
Pregnant or breastfeeding women

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00319982

Locations

United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Children's Hospital
Boston, Massachusetts, United States, 02115

Sponsors and Collaborators

Brigham and Women's Hospital

National Heart, Lung, and Blood Institute (NHLBI)

Children's Hospital Boston

Investigators

Principal Investigator:

Carolyn Y Ho, MD

Brigham and Women's Hospital

More Information

Publications:

Fatkin D, McConnell BK, Mudd JO, Semsarian C, Moskowitz IG, Schoen FJ, Giewat M, Seidman CE, Seidman JG. An abnormal Ca(2+) response in mutant sarcomere protein-mediated familial hypertrophic cardiomyopathy. J Clin Invest. 2000 Dec;106(11):1351-9.

Semsarian C, Ahmad I, Giewat M, Georgakopoulos D, Schmitt JP, McConnell BK, Reiken S, Mende U, Marks AR, Kass DA, Seidman CE, Seidman JG. The L-type calcium channel inhibitor diltiazem prevents cardiomyopathy in a mouse model. J Clin Invest. 2002 Apr;109(8):1013-20.

Ho CY, Sweitzer NK, McDonough B, Maron BJ, Casey SA, Seidman JG, Seidman CE, Solomon SD. Assessment of diastolic function with Doppler tissue imaging to predict genotype in preclinical hypertrophic cardiomyopathy. Circulation. 2002 Jun 25;105(25):2992-7.

Ho CY, Seidman CE. A contemporary approach to hypertrophic cardiomyopathy. Circulation. 2006 Jun 20;113(24):e858-62. Review. No abstract available.

Nagueh SF, McFalls J, Meyer D, Hill R, Zoghbi WA, Tam JW, Quinones MA, Roberts R, Marian AJ. Tissue Doppler imaging predicts the development of hypertrophic cardiomyopathy in subjects with subclinical disease. Circulation. 2003 Jul 29;108(4):395-8. Epub 2003 Jul 14.

Responsible Party:	Carolyn Ho, MD, Brigham and Women's Hospital
ClinicalTrials.gov Identifier:	NCT00319982 History of Changes
Other Study ID Numbers:	001936
Study First Received:	April 27, 2006
Last Updated:	June 22, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Brigham and Women's Hospital:

Hypertrophic Cardiomyopathy
Left ventricular hypertrophy
Diltiazem

Additional relevant MeSH terms:

Cardiomyopathy, Hypertrophic
Hypertrophy
Cardiomyopathies
Heart Diseases
Cardiovascular Diseases
Aortic Stenosis, Subvalvular
Aortic Valve Stenosis
Heart Valve Diseases
Pathological Conditions, Anatomical
Diltiazem

Verapamil
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Antihypertensive Agents
Vasodilator Agents
Anti-Arrhythmia Agents

ClinicalTrials.gov processed this record on February 12, 2012