Role of Anti-TREK-1 Autoantibodies in SCVF (TRACK-VF)

Circulating Anti-TREK-1 Autoantibodies as Diagnostic and Prognostic Biomarkers in Short-Coupled Ventricular Fibrillation

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Idiopathic Ventricular Fibrillation; Short-coupled Ventricular Fibrillation
• Intervention / Treatment: Other: Repeat plasma screening for the presence or absence of anti-TREK-1 autoantibodies; Genetic: DPP6 risk haplotype

Detailed Description

Please refer to the uploaded study protocol

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V4G5
    • Institut Universitaire de Cardiologie et Pneumologie de Quebec

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Cohort study of SCVF probands

Description

Inclusion Criteria:

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

Exclusion Criteria:

- SCVF patients < age 18

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

SCVF; Probands with diagnosis of SCVF

Other: Repeat plasma screening for the presence or absence of anti-TREK-1 autoantibodies; Semiquantitative measure of circulating anti-TREK-1 autoantibodies in plasma of study participants using a peptid microarray; Genetic: DPP6 risk haplotype; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-dependent variability of plasma concentrations of anti-TREK-1 autoantibodies	Repeat plasma sampling to assess the presence/absence of anti-TREK-1 autoantibodies and time-dependent variability of antibody expression	12 months
Impact of anti-TREK-1 autoantibodies on disease severity	Correlation of the presence (plasma concentration) of anti-TREK-1 autoantibodies with recurrent VF, electrical storm and appropriate ICD therapies	12 months

Collaborators and Investigators

• Sponsor: Institut universitaire de cardiologie et de pneumologie de Québec, University Laval
• Investigators: Principal Investigator: Christian Steinberg, MD, Institut universitaire de cardiologie et de pneumologie de Québec, University Laval

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2025
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: April 6, 2025
• First Submitted That Met QC Criteria: April 16, 2025
• First Posted (Actual): April 24, 2025

Study Record Updates

• Last Update Posted (Actual): April 24, 2025
• Last Update Submitted That Met QC Criteria: April 16, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: SCVF; anti-TREK-1
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Ventricular Fibrillation; Immunologic Factors; Physiological Effects of Drugs; Autoantibodies
• Other Study ID Numbers: MP-10-2025-4338

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No