NCT02045043

Brief Summary

Arrhythmias remain a major health problem, causing at least 250,000 deaths annually in the United States. Pharmacological treatments often do more harm than good, and device therapies are limited by high cost and effects on quality of life. Ion channel mutations cause rare inherited arrhythmopathies, but account for only a small fraction of patients with life- threatening arrhythmias and sudden death. Most arrhythmias occur during myocardial ischemia, following myocardial infarction, and in patients with poor left ventricular (LV) function of any etiology. Aside from ejection fraction (EF), few clinically useful indicators to stratify the risk of sudden death have been identified. The role of subtle difference in ion channel expression and/or structure in predisposing patients to arrhythmias and modulating the risk of sudden death is unknown. In this study, we are prospectively testing whether polymorphisms in ion channels and ion channel modifying genes are associated with arrhythmias in a population with internal cardioverter-defibrillators (ICDs) and poor LV function. We will test the hypothesis that functional polymorphisms in the coding sequences and promoter regions of cardiac genes (e.g. ion channels, beta-adrenergic receptors) predispose individuals to arrhythmias and /or heart failure progression. We hope to identify genetic predictors for the common forms of sudden cardiac death. This would allow the identification of a subpopulation of heart failure patients that would benefit most from ICD placement.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,807

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Mar 2002

Longer than P75 for all trials

Geographic Reach
1 country

6 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2002

Completed
10.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2012

Completed
1.6 years until next milestone

First Submitted

Initial submission to the registry

January 22, 2014

Completed
2 days until next milestone

First Posted

Study publicly available on registry

January 24, 2014

Completed
Last Updated

January 24, 2014

Status Verified

January 1, 2014

Enrollment Period

10.3 years

First QC Date

January 22, 2014

Last Update Submit

January 22, 2014

Conditions

Sudden Cardiac DeathArrhythmiasCongestive Heart FailureCardiomyopathy

Keywords

Sudden Cardiac DeathArrhythmiasCongestive Heart FailureCardiomyopathySingle Nucleotide PolymorphismsGenomics

Outcome Measures

Primary Outcomes (1)

  • Shock-Free Survival

    Time to first appropriate shock from an Implantable Cardioverter-Defibrillator

    Up to 5 years

Secondary Outcomes (3)

  • Survival

    Up to 5 years

  • Transplant- and VAD-Free Survival

    Up to 5 years

  • Appropriate Shock Frequency

    Up to 5 years

Study Arms (1)

Cardiomyopathy patients with ICDs

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Subjects 18 years of age and over with a cardiomyopathy, an ejection fraction less than or equal to 30%, and an implantable cardioverter defibrillator

You may qualify if:

  • An ICD placed during the last 5 years, or a planned ICD within 1 month
  • Age 18 or older
  • Left Ventricular Ejection fraction \< or = 30%
  • Ability to give informed consent

You may not qualify if:

  • Patient refuses or is unable to give consent
  • A life expectancy \<6 months from a non-cardiac life threatening disease
  • Ongoing Class IV heart failure symptoms despite treatment
  • History of cardiac transplant or left ventricular assist device

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

Emory University

Atlanta, Georgia, 30322, United States

Location

Massuchetts General Hospital

Boston, Massachusetts, 02114, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Mid Ohio Cardiology

Columbus, Ohio, 43214, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

VA Pittsburgh Healthcare System

Pittsburgh, Pennsylvania, 15240, United States

Location

Related Publications (5)

  • Refaat MM, Lubitz SA, Makino S, Islam Z, Frangiskakis JM, Mehdi H, Gutmann R, Zhang ML, Bloom HL, MacRae CA, Dudley SC, Shalaby AA, Weiss R, McNamara DM, London B, Ellinor PT. Genetic variation in the alternative splicing regulator RBM20 is associated with dilated cardiomyopathy. Heart Rhythm. 2012 Mar;9(3):390-6. doi: 10.1016/j.hrthm.2011.10.016. Epub 2011 Oct 17.

    PMID: 22004663BACKGROUND

  • Blanco RR, Austin H, Vest RN 3rd, Valadri R, Li W, Lassegue B, Song Q, London B, Dudley SC, Bloom HL, Searles CD, Zafari AM. Angiotensin receptor type 1 single nucleotide polymorphism 1166A/C is associated with malignant arrhythmias and altered circulating miR-155 levels in patients with chronic heart failure. J Card Fail. 2012 Sep;18(9):717-23. doi: 10.1016/j.cardfail.2012.06.531. Epub 2012 Aug 9.

    PMID: 22939041RESULT

  • Bloom HL, Shukrullah I, Veledar E, Gutmann R, London B, Dudley SC. Statins Decrease Oxidative Stress and ICD Therapies. Cardiol Res Pract. 2010;2010:253803. doi: 10.4061/2010/253803. Epub 2010 Mar 25.

    PMID: 20369058RESULT

  • Aleong RG, Mulvahill MJ, Halder I, Carlson NE, Singh M, Bloom HL, Dudley SC, Ellinor PT, Shalaby A, Weiss R, Gutmann R, Sauer WH, Narayanan K, Chugh SS, Saba S, London B. Left Ventricular Dilatation Increases the Risk of Ventricular Arrhythmias in Patients With Reduced Systolic Function. J Am Heart Assoc. 2015 Jul 31;4(8):e001566. doi: 10.1161/JAHA.114.001566.

    PMID: 26231842DERIVED

  • AlJaroudi WA, Refaat MM, Habib RH, Al-Shaar L, Singh M, Gutmann R, Bloom HL, Dudley SC, Ellinor PT, Saba SF, Shalaby AA, Weiss R, McNamara DM, Halder I, London B; Genetic Risk Assessment of Defibrillator Events Investigators. Effect of angiotensin-converting enzyme inhibitors and receptor blockers on appropriate implantable cardiac defibrillator shock in patients with severe systolic heart failure (from the GRADE Multicenter Study). Am J Cardiol. 2015 Apr 1;115(7):924-31. doi: 10.1016/j.amjcard.2015.01.020. Epub 2015 Jan 15.

    PMID: 25682436DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Blood was obtained for DNA (all subjects) and serum (subgroup of subjects)

MeSH Terms

Conditions

Death, Sudden, CardiacArrhythmias, CardiacHeart FailureCardiomyopathies

Condition Hierarchy (Ancestors)

Heart ArrestHeart DiseasesCardiovascular DiseasesDeath, SuddenDeathPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Barry London, MD PhD

    University of Iowa

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Director, Division of Cardiovascular Medicine

Study Record Dates

First Submitted

January 22, 2014

First Posted

January 24, 2014

Study Start

March 1, 2002

Primary Completion

June 1, 2012

Study Completion

June 1, 2012

Last Updated

January 24, 2014

Record last verified: 2014-01

Locations

US(6)