Treatment of Preclinical Hypertrophic Cardiomyopathy With Diltiazem

This study has been completed.
Sponsor:
Collaborators:
Children's Hospital Boston
Information provided by (Responsible Party):
Carolyn Yung Ho, MD, Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
NCT00319982
First received: April 27, 2006
Last updated: March 24, 2015
Last verified: March 2015
  Purpose

This is a pilot clinical trial 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, and therefore without a clinical diagnosis of HCM.

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, as well as exploratory analyses of a broad range of features reflecting the heart's structure and function.


Condition Intervention Phase
Hypertrophic Cardiomyopathy
Drug: Diltiazem
Drug: Placebo
Phase 2
Phase 3

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: Treatment of Preclinical Hypertrophic Cardiomyopathy With Diltiazem

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Increase, Stability of, or Decrease in the Decline of Diastolic Function as Reflected by the Global Early Myocardial Relaxation (E') Velocity [ Time Frame: Baseline and final study visits ] [ Designated as safety issue: No ]
    The change in E' velocity (difference between final value - baseline value) was compared between participants who received diltiazem and those who received placebo to gauge treatment response. Please note that the total duration on treatment varied between study subjects to maximize time on treatment for the trial. Specifically, subjects that enrolled earliest had the longest duration of treatment; those who enrolled latest had the shortest duration of treatment with a minimum treatment duration of 1 year. All analyses examine the final study visit on treatment to the baseline visit.


Secondary Outcome Measures:
  • Safety and Tolerability of Diltiazem Treatment [ Time Frame: Baseline through final study visits ] [ Designated as safety issue: Yes ]
    Adverse events were compared between participants assigned to diltiazem and those assigned to placebo

  • Impact of Diltiazem on Heart Rate [ Time Frame: Baseline and final study visits ] [ Designated as safety issue: Yes ]
    Change in Value (Difference between Final and Baseline Visits)

  • Left Ventricular Cavity Size [ Time Frame: Baseline and final study visits ] [ Designated as safety issue: No ]
    Change in Left Ventricular End-Diastolic Diameter z-score (Final Value - Baseline Value)

  • Development of Left Ventricular Hypertrophy [ Time Frame: Baseline through final study visits ] [ Designated as safety issue: No ]
    The number of participants who developed overt left ventricular hypertrophy during the duration of the trial was analyzed

  • Adherence to Study Medication [ Time Frame: Duration of the trial ] [ Designated as safety issue: No ]
    Adherence to study medication was assessed by pill count

  • Impact of Diltiazem on Systolic Blood Pressure [ Time Frame: Baseline and final study visits ] [ Designated as safety issue: Yes ]
    Change in Value (Difference between Final and Baseline Visits)


Enrollment: 39
Study Start Date: January 2006
Study Completion Date: December 2013
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: I- Diltiazem
Diltiazem- study medication
Drug: Diltiazem
Sustained release formulation titrated to a target dose of 360 mg daily, or a maximum of 5 mg/kg/day in pediatric subjects for the duration of the study period
Other Name: Diltiazem
Placebo Comparator: II- Placebo
Placebo Comparator
Drug: Placebo
Placebo comparator (double-blind allocation of study medication)
Other Name: Placebo

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Children's Hospital Boston
Investigators
Principal Investigator: Carolyn Y Ho, MD Brigham and Women's Hospital
  More Information

Publications:

Responsible Party: Carolyn Yung Ho, MD, Associate Physician, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT00319982     History of Changes
Other Study ID Numbers: 001936, K23HL078901
Study First Received: April 27, 2006
Results First Received: January 26, 2015
Last Updated: March 24, 2015
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
Cardiomyopathies
Hypertrophy
Aortic Stenosis, Subvalvular
Aortic Valve Stenosis
Cardiovascular Diseases
Heart Diseases
Heart Valve Diseases
Pathological Conditions, Anatomical
Diltiazem
Antihypertensive Agents
Calcium Channel Blockers
Cardiovascular Agents
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on July 01, 2015