Role of Anti-TREK-1 Autoantibodies in SCVF

NCT06943365 | Recruiting

• 1 other identifier: MP-10-2025-4338
• Study Type: observational
• Target: 300
• Locations: 2 countries
• Sites: 5

Brief Summary

Short-coupled ventricular fibrillation (SCVF) is a lethal, primary electrical disorder and an important cause of unexplained cardiac arrest.1 Recent work from our group suggests that a substantial proportion of SCVF cases is associated to circulating autoantibodies targeting TREK-1, a cardiac potassium channel, resulting in an abnormal gain-of-function which is the prerequisite for the SCVF phenotype.2 This proposal is a translational multicenter study to validate anti-TREK-1 autoantibodies as a diagnostic and prognostic biomarker in a large, diversified cohort of SCVF patients (Figure 1). Functional, cellular experiments in patient-derived hiPSC cardiomyocytes and Purkinje cells will be performed to explore the cell type-specific role of TREK-1 in arrhythmogenesis, while single-nuclear RNA sequencing (snRNA-seq) will allow us to establish the transcriptomic profile (Figure 1). These results will identify the cellular substrate for SCVF.

Conditions

Short-coupled Ventricular Fibrillation; Idiopathic Ventricular Fibrillation

Keywords

SCVF; anti-TREK-1 antibodies; IVF

Outcome Measures

Primary Outcomes (1)

• Presence of anti-TREK-1 autoantibodies at three different time points

  Plasma concentrations of anti-TREK-1 autoantibodies (semiquantitative measure using a peptide microarray at three predefined time points

  12 months

Secondary Outcomes (2)

• Time-dependent variability of plasma concentrations of anti-TREK-1 autoantibodies

  12 months

• Impact of anti-TREK-1 autoantibodies on disease severity

  12 months

Study Arms (3)

SCVF

Probands with diagnosis of SCVF

Other: Repeat plasma screening for the presence or absence of anti-TREK-1 autoantibodies; Genetic: DPP6 risk haplotype

IVF

Otherwise unexplained idiopathic ventricular fibrillation

Other: Repeat plasma screening for the presence or absence of anti-TREK-1 autoantibodies; Genetic: DPP6 risk haplotype

Control group

Unaffected healthy individuals matched for age, sex and ethnicity

Other: Repeat plasma screening for the presence or absence of anti-TREK-1 autoantibodies

Interventions

Repeat plasma screening for the presence or absence of anti-TREK-1 autoantibodies OTHER

Semiquantitative measure of circulating anti-TREK-1 autoantibodies in plasma of study participants using a peptid microarray

Control group; IVF; SCVF

DPP6 risk haplotype GENETIC

Systematic genetic screening for the Dutch DPP6 risk haplotype in all study participants and correlation of results with the presence or absence of anti-TREK-1 autoantibodies

IVF; SCVF

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Cohort study of SCVF probands

You may qualify if:

• Age ≥ 18 years
• Diagnosis of SCVF as per current criteria
• Willingness to provide written informed consent

You may not qualify if:

• \- SCVF patients \< age 18

Sponsors & Collaborators

• Institut universitaire de cardiologie et de pneumologie de Québec, University Laval: lead

Study Sites (5)

St-Paul's Hospital - University of British Columbia

Vancouver, British Columbia, Canada

NOT YET RECRUITING

PHRI

Hamilton, Ontario, Canada

ACTIVE NOT RECRUITING

Ottawa Heart Center

Ottawa, Ontario, Canada

NOT YET RECRUITING

Institut universitaire de cardiologie et pneumologie de Québec

Québec, Quebec, G1V4G5, Canada

RECRUITING

Amsterdam University Medical Center

Amsterdam, Netherlands

ACTIVE NOT RECRUITING

Related Publications (3)

• Steinberg C. Short-Coupled Ventricular Fibrillation. Card Electrophysiol Clin. 2023 Sep;15(3):331-341. doi: 10.1016/j.ccep.2023.05.004. Epub 2023 Jun 18.

  PMID: 37558303 BACKGROUND

• Steinberg C, Davies B, Mellor G, Tadros R, Laksman ZW, Roberts JD, Green M, Alqarawi W, Angaran P, Healey J, Sanatani S, Leather R, Seifer C, Fournier A, Duff H, Gardner M, McIntyre C, Hamilton R, Simpson CS, Krahn AD. Short-coupled ventricular fibrillation represents a distinct phenotype among latent causes of unexplained cardiac arrest: a report from the CASPER registry. Eur Heart J. 2021 Jul 31;42(29):2827-2838. doi: 10.1093/eurheartj/ehab275.

  PMID: 34010395 BACKGROUND

• Li J, Janin A, Patoughi M, Gaudreault N, Kis L, Moha Ou Maati H, Bosse Y, Steinberg C. Circulating Autoantibodies Targeting TREK-1 in Patients With Short-Coupled Ventricular Fibrillation. Circulation. 2024 Dec 10;150(24):1944-1954. doi: 10.1161/CIRCULATIONAHA.124.070284. Epub 2024 Sep 24.

  PMID: 39315453 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Repeat plasma samples

MeSH Terms

Conditions

Paroxysmal ventricular fibrillation

Study Officials

• Christian Steinberg, MD

  Institut universitaire de cardiologie et de pneumologie de Québec, University Laval

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marina Sanchez, PhD

CONTACT

+14186568711; marina.sanchez@criucpq.ulaval.ca

Paule Banville, Study coordinator

CONTACT

+14186568711; paule.banville@criucpq.ulaval.ca

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 24 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: April 6, 2025
• First Posted: April 24, 2025
• Study Start: May 1, 2025
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: June 16, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (4); NL (1)