Worm Study: Modifier Genes in Sudden Cardiac Death

Worm Study: Identification of Modifier Genes in a Unique Founder Population With Sudden Cardiac Death

Quest for modifier genes associated with ventricular arrhythmias in presence of a cardiac sodium channel gene (SCN5A-delPhe1617) mutation.

Study Overview

• Status: Recruiting
• Conditions: Brugada Syndrome; Long QT Syndrome 3
• Intervention / Treatment: Procedure: Dermal biopsy; Behavioral: Gastro-intestinal questionnaire; Genetic: Whole-exome sequencing

Detailed Description

In a large Dutch SCN5A founder population with malignant ventricular arrhythmias, the investigators aim to identify genetic modifiers by means of whole-exome sequencing and to establish a comprehensive genotype-phenotype correlation, focussing on clinical and cellular electrophysiological characteristics and neurocardiac modulation.

• Study Type: Interventional
• Enrollment (Anticipated): 223
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rachel ter Bekke, M.D.; Phone Number: +31433877098; Email: rachel.ter.bekke@mumc.nl
• Study Contact Backup: Name: Paul Volders, M.D., Ph.D.; Phone Number: +31433877097; Email: p.volders@maastrichtuniversity.nl

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6202 AZ
      • Recruiting
      • Maastricht University Medical Center
      • Contact: ter Bekke; Phone Number: +31433877098; Email: rachel.ter.bekke@mumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria (mutation carrier group):

• Age ≥ 18 years.
• Heterozygous or homozygous carriership of SCN5A-delPhe1617.
• Confirmed kinship to the founder population by haplotype analysis using predefined microsatellite markers.
• Written informed consent.

Inclusion Criteria (non-mutation carrier group):

• Age ≥ 18 years.
• Non SCN5A-delPhe1617 genotype.
• Confirmed kinship to the Founder Group by haplotype analysis using predefined microsatellite marker.
• Written informed consent.

Inclusion criteria Spouse Group

• Age ≥ 18 years.
• Biological parent of SCN5A-delPhe1617 positive subject participating to the Worm Study, and not belonging to study group 1 or 2.
• Written informed consent.

Exclusion Criteria:

• Age ≥ 18 years.
• Biological parent of SCN5A-delPhe1617 positive subject participating to the Worm Study, and not belonging to study group 1 or 2.
• Written informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Mutation Carriers; Whole-exome sequencing (WES) Dermal biopsy Gastro-intestinal questionnaire	Procedure: Dermal biopsy; Skin biopsy; Behavioral: Gastro-intestinal questionnaire; Pagi-Sym, Bristol Stool Chart, gastrointestinal symptom rating scale (GSRS); Genetic: Whole-exome sequencing; Whole-exome sequencing (WES)
Placebo Comparator: Non-Mutation Carriers; Whole-exome sequencing (WES) Gastro-intestinal questionnaire	Behavioral: Gastro-intestinal questionnaire; Pagi-Sym, Bristol Stool Chart, gastrointestinal symptom rating scale (GSRS); Genetic: Whole-exome sequencing; Whole-exome sequencing (WES)
Other: Spouse; Whole-exome sequencing (WES) 12-Lead ECG	Genetic: Whole-exome sequencing; Whole-exome sequencing (WES)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Difference in genetic profile (e.g. modifier genes) between mutation carriers expressing different phenotypes and non-mutation carriers.	two years

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Collaborators: Netherlands Heart Foundation
• Investigators: Study Director: Paul Volders, M.D., Ph.D., Maastricht University Medical Centre

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (Anticipated): April 1, 2025
• Study Completion (Anticipated): April 1, 2025

Study Registration Dates

• First Submitted: December 9, 2013
• First Submitted That Met QC Criteria: December 12, 2013
• First Posted (Estimate): December 19, 2013

Study Record Updates

• Last Update Posted (Estimate): May 14, 2015
• Last Update Submitted That Met QC Criteria: May 13, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Death, Sudden; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Heart Defects, Congenital; Cardiovascular Abnormalities; Heart Arrest; Syndrome; Death; Death, Sudden, Cardiac; Brugada Syndrome; Long QT Syndrome
• Other Study ID Numbers: METC 142060