Clinical trial NCT06943365: Role of Anti-TREK-1 Autoantibodies in SCVF
Official title: Circulating Anti-TREK-1 Autoantibodies as Diagnostic and Prognostic Biomarkers in Short-Coupled Ventricular Fibrillation
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Short-coupled Ventricular Fibrillation
Idiopathic Ventricular Fibrillation
Keywords: SCVF
anti-TREK-1
Lead sponsor: Institut universitaire de cardiologie et de pneumologie de Québec, University Laval
Sponsor class: OTHER
First posted: 2025-04-24
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Cohort study of SCVF probands

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.

Detailed description: Please refer to the uploaded study protocol

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

- SCVF patients \< age 18

Primary outcomes:
measure: Presence of anti-TREK-1 autoantibodies at three different time points
timeFrame: 12 months
Secondary outcomes:
measure: Time-dependent variability of plasma concentrations of anti-TREK-1 autoantibodies
timeFrame: 12 months
measure: Impact of anti-TREK-1 autoantibodies on disease severity
timeFrame: 12 months
Other outcomes:
Locations:
city: Quebec
country: Canada
facility: Institut universitaire de cardiologie et pneumologie de Québec
Study officials:
affiliation: Institut universitaire de cardiologie et de pneumologie de Québec, University Laval
name: Christian Steinberg, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.