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The Leiden Nonischemic Cardiomyopathy Study

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by Leiden University Medical Center
Sponsor:
Information provided by (Responsible Party):
Katja Zeppenfeld, Leiden University Medical Center
ClinicalTrials.gov Identifier:
NCT01940081
First received: August 29, 2013
Last updated: September 7, 2013
Last verified: September 2013
  Purpose

Rationale: Sudden cardiac death, mainly caused by ventricular arrhythmias (VA), is a major cause of morbidity and mortality in non-ischemic cardiomyopathy (NICM). Therapies that effectively prevent VA are lacking. Improved understanding of the substrate and mechanisms of VA in NICM may allow more effective, individualized and substrate-based therapies to be developed. In addition, risk stratification in NICM needs to be improved so that therapies can be allocated more efficiently.

Objectives: 1) To improve our understanding of the underlying pro-arrhythmic substrate and electrophysiologic mechanisms of VA in NICM, and to develop individualized treatment for VA based on the identified substrate. 2) To improve risk stratification for VA and sudden cardiac death in NICM based on substrate characteristics. 3) to evaluate disease progression in NICM.

Hypothesis: Improved understanding of the substrate and mechanisms of VA in NICM may allow more effective, individualized and substrate-based therapies to be developed.

Study design: A prospective cohort study.

Study population: The study population will consist of three groups (A, B and C): NICM patients with documented VA, suspected VA or intermediate to high risk for VA (according to established criteria) who are not referred for cardiac surgery (group A), NICM patients with documented VA, suspected VA or a high risk for VA who are referred for cardiac surgery (group B) and a control group consisting of patients without NICM who are referred for cardiac surgery (group C).

Evaluation: All patients will be evaluated according to current standards for patients with NICM. Evaluation will include 24h-Holter, echocardiography, coronary angiogram and contrast-enhanced MRI (CE-MRI). If CE-MRI is performed in another hospital, additional recordings will be performed in our hospital. Additionally, blood samples (arterial, cardiac venous and peripheral venous) for collagen turnover markers will be taken from all patients. 123-iodine metaiodobenzylguanidine (123-I MIBG) imaging, electrophysiologic study and endomyocardial biopsy will be performed in group A and B. Intra-operative biopsy will be performed in group B and C.

Intervention: In group B, intra-operative mapping and cryo-ablation and postoperative electrophysiologic study will be performed in patients with subepicardial late enhancement on MRI or induced VA suspected for an subepicardial origin.

Main study parameters/endpoints: The main study parameters are extent, location and pattern of fibrosis on imaging and in biopsy specimens. The main study endpoints are inducibility of VA, type of induced VA, spontaneous VA and type of spontaneous VA.


Condition Intervention
Cardiomyopathy, Dilated
Tachycardia, Ventricular
Ventricular Fibrillation
Other: Transthoracic echocardiography
Other: Exercise test
Other: 24-hour Holter electrocardiogram
Other: Contrast-enhanced magnetic resonance imaging
Other: 123-iodine metaiodobenzylguanidine imaging
Other: Blood samples
Genetic: Genetic analysis
Procedure: Invasive electrophysiological study
Procedure: Endomyocardial biopsy
Procedure: Intraoperative biopsy
Procedure: Intraoperative mapping and/or ablation

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Leiden Nonischemic Cardiomyopathy Study

Resource links provided by NLM:


Further study details as provided by Leiden University Medical Center:

Primary Outcome Measures:
  • Inducibility of ventricular arrhythmias [ Time Frame: Baseline electrophysiological study ] [ Designated as safety issue: No ]
  • Type of induced ventricular arrhythmias [ Time Frame: Baseline electrophysiological study ] [ Designated as safety issue: No ]
  • Spontaneous ventricular arrhythmias [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  • Type of spontaneous ventricular arrhythmias [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Hospital admissions for heart failure [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  • Cardiac mortality [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  • All-cause mortality [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  • LV function/dimensions/compact fibrosis deterioration as assessed by 123-I MIBG imaging and/or CE-MRI [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Per patient:

Blood samples (40 mL) Ventricular biopsies


Estimated Enrollment: 220
Study Start Date: October 2011
Estimated Study Completion Date: October 2021
Estimated Primary Completion Date: October 2021 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Group A: Nonischemic cardiomyopathy - not admitted for surgery

Patients with nonischemic cardiomyopathy with:

  • documented ventricular arrhythmia or
  • suspected ventricular arrhythmia (e.g. because of out-of-hospital cardiac arrest, palpitations or syncope) or
  • high risk for ventricular arrhythmia (LVEF ≤ 35%) or
  • intermediate risk for ventricular arrhythmia (LVEF ≤ 50% and late enhancement on contrast-enhanced MRI)

who are not admitted for cardiac surgery

Other: Transthoracic echocardiography Other: Exercise test Other: 24-hour Holter electrocardiogram Other: Contrast-enhanced magnetic resonance imaging Other: 123-iodine metaiodobenzylguanidine imaging Other: Blood samples Genetic: Genetic analysis Procedure: Invasive electrophysiological study Procedure: Endomyocardial biopsy
Group B: Nonischemic cardiomyopathy -admitted for surgery

Patients with nonischemic cardiomyopathy with:

  • documented ventricular arrhythmia or
  • suspected ventricular arrhythmia (e.g. because of out-of-hospital cardiac arrest, palpitations or syncope) or
  • high risk for ventricular arrhythmia (LVEF ≤ 35%)

who are admitted for cardiac surgery (e.g., mitral valve annuloplasty or CorCap)

Other: Transthoracic echocardiography Other: Exercise test Other: 24-hour Holter electrocardiogram Other: Contrast-enhanced magnetic resonance imaging Other: 123-iodine metaiodobenzylguanidine imaging Other: Blood samples Genetic: Genetic analysis Procedure: Invasive electrophysiological study Procedure: Intraoperative biopsy Procedure: Intraoperative mapping and/or ablation
Group C: Controls

Patients without nonischemic cardiomyopathy (controls) who are admitted for:

  • Coronary artery bypass graft surgery and who do not have prior myocardial infarction
  • Aortic valve replacement
Other: Transthoracic echocardiography Other: Exercise test Other: 24-hour Holter electrocardiogram Other: Contrast-enhanced magnetic resonance imaging Other: Blood samples Procedure: Intraoperative biopsy

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Patients with nonischemic cardiomyopathy and controls who are admitted to the hospital

Criteria

Inclusion criteria, group A:

  • Nonischemic cardiomyopathy
  • Documented ventricular arrhythmia, suspected ventricular arrhythmia (e.g. because of out-of-hospital cardiac arrest, palpitations or syncope) or high risk for ventricular arrhythmias (LVEF ≤ 35%) or intermediate risk for ventricular arrhythmias (LVEF ≤ 50% and late enhancement on contrast-enhanced MRI)
  • Admission not for cardiac surgery

Inclusion criteria, group B:

  • Nonischemic cardiomyopathy
  • Documented ventricular arrhythmia or suspected ventricular arrhythmia (e.g. because of out-of-hospital cardiac arrest, palpitations or syncope) or high risk for ventricular arrhythmia (LVEF ≤ 35%)
  • Admission for cardiac surgery (e.g., mitral valve annuloplasty or CorCap)

Inclusion criteria, group C:

- Patients undergoing aortic valve replacement or coronary artery bypass graft surgery

Exclusion criteria, all groups:

  • Age < 18 years or > 80 years
  • Inadequate patient competence
  • Pregnancy
  • Inability to comply with the protocol due to haemodynamic instability

Exclusion Criteria, groups A and B:

- Other cardiomyopathy (e.g., prior myocardial infarction, infiltrative cardiac disease such as sarcoidosis, amyloidosis or Chagas cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy/dysplasia, hypertrophic cardiomyopathy, non-compaction cardiomyopathy and congenital heart disease)

Exclusion criteria, group C:

  • Nonischemic cardiomyopathy
  • Prior myocardial infarction
  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: NCT01940081

Locations
Netherlands
Dept. of Cardiology, Leiden University Medical Center Recruiting
Leiden, Netherlands
Contact: K Zeppenfeld, MD, PhD    0031715266933    k.zeppenfeld@lumc.nl   
Principal Investigator: Katja Zeppenfeld, MD, PhD         
Sub-Investigator: Sebastiaan Piers, MD         
Sponsors and Collaborators
Leiden University Medical Center
  More Information

No publications provided

Responsible Party: Katja Zeppenfeld, Prof. dr., Leiden University Medical Center
ClinicalTrials.gov Identifier: NCT01940081     History of Changes
Other Study ID Numbers: Cardiomyopathy study
Study First Received: August 29, 2013
Last Updated: September 7, 2013
Health Authority: Netherlands: Medical Ethics Review Committee (METC)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Leiden University Medical Center:
Genetic Testing
Cardiomyopathy, Dilated
Tachycardia, Ventricular
Ventricular Fibrillation
Arrhythmias, Cardiac/etiology
Arrhythmias, Cardiac/physiopathology
Magnetic Resonance Imaging
3-Iodobenzylguanidine/diagnostic use
Sympathetic Nervous System/radionuclide imaging
Electrophysiologic Techniques, Cardiac
Biopsy
Echocardiography
Electrocardiography, Ambulatory
Exercise Test

Additional relevant MeSH terms:
Cardiomyopathies
Cardiomyopathy, Dilated
Tachycardia
Tachycardia, Ventricular
Ventricular Fibrillation
Arrhythmias, Cardiac
Cardiomegaly
Cardiovascular Diseases
Heart Diseases
Pathologic Processes
3-Iodobenzylguanidine
Antineoplastic Agents
Diagnostic Uses of Chemicals
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Radiopharmaceuticals
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014