Sodium Channel Splicing in Heart Failure Trial

NCT01185587 | Completed

• 1 other identifier: 2009-1187
• Study Type: observational
• Target: 147
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this research is to see if investigators can detect truncated mRNA splice variants of the cardiac voltage-gated sodium (Na+) channel gene, SCN5A, in patients with a weak heart (Heart Failure) with or without an implantable cardioverter-defibrillator (ICD) and compare them to patients with a normal heart. Hypothesis:

1. 1.Patients with reduced left ventricular ejection fraction have increased abundances truncated mRNA splice variants of the SCN5A gene, which portends to sodium channel dysfunction and an increased risk for sudden cardiac death.
2. 2.Patients with implantable cardioverter-defibrillator devices (ICDs) who have experienced shock therapy have increased abundances of truncated mRNA splice variants of the SCN5A gene compared to similar congestive heart failure patients who have not experienced shock therapy.

Conditions

Atrial Fibrillation; Atrial Flutter; Heart Failure

Keywords

SCN5A protein; voltage-gated Na+ channel

Outcome Measures

Primary Outcomes (1)

• Amount of sodium channel splice variants

  We will correlate the amount of white cell Na+ channel splice variants with ejection fraction in patients with an without heart failure and with the number of shocks in the patients with ICDs.

  At enrollment

Secondary Outcomes (3)

• ACE mRNA

  At enrollment

• Ang II mRNA

  At enrollment

• HIF-1α mRNA

  At enrollment

Study Arms (4)

healthy patients with a normal heart

patients with HF without an lCD

patients with HF and an ICD without shock

patients with HF and an ICD with shock

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Heart Failure and Device Clinics

You may qualify if:

• All patients must be greater than 18 years of age
• Patients with reduced left ventricular function (i.e., heart failure patients) must have acquired heart failure and an ejection fraction less than 35% documented in the last two years by any methodology
• Control population patients must be free of heart failure symptoms, diastolic dysfunction, and left ventricular systolic dysfunction documented by any methodology within 1 year of study enrollment
• Patients with an ICD in place for more than 1 year and evidence of ICD events
• Patients with an ICD in place for more than 1 year and no evidence of ICD events
• All patients must be able to give informed consent

You may not qualify if:

• Patients less than 18 years of age.
• History of congenital heart disease as cause of impaired left ventricular function.
• Control patients with impaired left ventricular systolic function or the presence of diastolic dysfunction.
• Control or Study group patients with a history of congenital electrophysiological disorders like the long-QT syndrome or Brugada disease will not be included.
• Control or Study group patients who require antiarrhythmic drugs other than Vaughn-Williams Class II and IV agents.
• Control patients with a history of significant illness that may otherwise impair cardiac function within 12 months of study enrollment. These conditions include: myocardial infarction, cardiac hospitalization, cardiac arrhythmia, infection, or cancer.
• ICD patients suffering from any other terminal or chronic inflammatory illness.
• Patients taking immunosuppressive medications, have chronic infection, or have an acute or chronic inflammatory illness that might alter white cell mRNA expression.
• Patients with any illness expected to result in death within 18 months of enrollment.
• Patients with white blood cell dyscrasia or cancers.
• Current illicit drug use.
• Inability to give informed consent.

Sponsors & Collaborators

• University of Illinois at Chicago: lead
• Jesse Brown VA Medical Center: collaborator

Study Sites (2)

Jesse Brown VA Medical Center

Chicago, Illinois, 60612, United States

Location

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location

Related Publications (1)

• Gao G, Brahmanandam V, Raicu M, Gu L, Zhou L, Kasturirangan S, Shah A, Negi SI, Wood MR, Desai AA, Tatooles A, Schwartz A, Dudley SC Jr. Enhanced risk profiling of implanted defibrillator shocks with circulating SCN5A mRNA splicing variants: a pilot trial. J Am Coll Cardiol. 2014 Jun 3;63(21):2261-9. doi: 10.1016/j.jacc.2014.02.588. Epub 2014 Apr 2.

  PMID: 24703920 RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

Whole blood

MeSH Terms

Conditions

Atrial Fibrillation; Atrial Flutter; Heart Failure

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Samuel C. Dudley, Jr., MD, PhD

  University of Illinois at Chicago

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 17, 2010
• First Posted: August 20, 2010
• Study Start: February 1, 2010
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: April 23, 2014

Record last verified: 2014-04

Locations

US (2)