International CRDS Registry

NCT06508164 | Recruiting

• 1 other identifier: 16861
• Study Type: observational
• Target: 500
• Locations: 8 countries
• Sites: 16

Brief Summary

Calcium Release Deficiency Syndrome (CRDS) is a newly discovered genetic arrhythmia syndrome that confers a risk of life-threatening arrhythmias secondary to RYR2 loss-of-function. The International CRDS registry has been designed to facilitate large-scale evaluation of CRDS, including its phenotypic spectrum, approaches to risk stratification, and optimal treatment strategies.

Conditions

Calcium Release Deficiency Syndrome

Outcome Measures

Primary Outcomes (1)

• Malignant Ventricular Arrhythmia

  Composite of malignant syncope, ICD shock, cardiac arrest, and sudden cardiac death

  5 years

Study Arms (3)

CRDS

Possesses a rare RYR2 variant characterized to be loss-of-function based on in vitro testing consistent with a CRDS diagnosis

Carrier of an RYR2 truncating variant or large copy number variant

Possesses a rare RYR2 truncating variant and/or large copy number variant involving the RYR2 gene.

Carrier of a non-functional RYR2 rare variant

Possesses a rare RYR2 variant that is NOT loss-of-function based on in vitro testing and has a clinical phenotype that was considered compatible with CRDS

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The registry will enrol 3 separate cohorts. The primary cohort consists of CRDS cases. A CRDS case is defined as an individual that possesses a rare RYR2 variant proven to be loss-of-function on in vitro analysis. A second cohort consists of individuals that possess a rare RYR2 truncating variant or large copy number variant. The third cohort involves individuals suspected of having CRDS, however in vitro analysis revealed that their rare RYR2 variant did not impact function.

CRDS Cohort Inclusion Criterion: \- Presence of a rare\* RYR2 variant that is characterized to be loss-of-function based on in vitro testing# RYR2 Truncating and Large CNV Cohort Inclusion Criterion: \- Presence of a rare\* RYR2 truncating variant and/or large copy number variant involving the RYR2 gene. Carriers of a Non-Functional RYR2 variant Inclusion Criterion: \- Presence of a rare\* RYR2 variant that is characterized to be neither loss- nor gain-of-function based on in vitro testing# \*rare defined as gnomAD prevalence \< 0.1% #RYR2 in vitro functional testing will be performed in the laboratory of Dr. Wayne Chen (University of Calgary)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Population Health Research Institute: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (16)

University of California

San Francisco, California, 94143, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

Duke University

Durham, North Carolina, 27710, United States

RECRUITING

Garvan Institute of Medical Research

Darlinghurst, New South Wales, 2010, Australia

RECRUITING

Antwerp University Hospital

Edegem, Antwerp, 2650, Belgium

RECRUITING

Universitair Ziekenhuis Brussel

Brussels, 1090, Belgium

RECRUITING

University of Calgary

Calgary, Alberta, T2N 1N4, Canada

RECRUITING

Children's & Women's Health Centre of British Columbia

Vancouver, British Columbia, V6H 3N1, Canada

RECRUITING

Hamilton General Hospital

Hamilton, Ontario, L8L 2X2, Canada

RECRUITING

London Health Sciences Centre - University Hospital

London, Ontario, N6A 5A5, Canada

RECRUITING

Montréal Heart Institute

Montreal, Quebec, H1T 1C8, Canada

RECRUITING

Institut Universitaire de Cardiologie et de Pneumologie de Québec-Université Laval

Québec, Quebec, Canada

RECRUITING

Aarhus University Hospital

Aarhus, DK-8200 N, Denmark

RECRUITING

CHU de Bordeaux

Bordeaux, Nouvelle-Aquitaine, 33404, France

RECRUITING

Shaare Zedek Medical Center

Jerusalem, 9103102, Israel

RECRUITING

City St George's, University of London

London, EC1V 0HB, United Kingdom

RECRUITING

Related Publications (6)

• Sun B, Yao J, Ni M, Wei J, Zhong X, Guo W, Zhang L, Wang R, Belke D, Chen YX, Lieve KVV, Broendberg AK, Roston TM, Blankoff I, Kammeraad JA, von Alvensleben JC, Lazarte J, Vallmitjana A, Bohne LJ, Rose RA, Benitez R, Hove-Madsen L, Napolitano C, Hegele RA, Fill M, Sanatani S, Wilde AAM, Roberts JD, Priori SG, Jensen HK, Chen SRW. Cardiac ryanodine receptor calcium release deficiency syndrome. Sci Transl Med. 2021 Feb 3;13(579):eaba7287. doi: 10.1126/scitranslmed.aba7287.

  PMID: 33536282 BACKGROUND

• Roston TM, Wei J, Guo W, Li Y, Zhong X, Wang R, Estillore JP, Peltenburg PJ, Noguer FRI, Till J, Eckhardt LL, Orland KM, Hamilton R, LaPage MJ, Krahn AD, Tadros R, Vinocur JM, Kallas D, Franciosi S, Roberts JD, Wilde AAM, Jensen HK, Sanatani S, Chen SRW. Clinical and Functional Characterization of Ryanodine Receptor 2 Variants Implicated in Calcium-Release Deficiency Syndrome. JAMA Cardiol. 2022 Jan 1;7(1):84-92. doi: 10.1001/jamacardio.2021.4458.

  PMID: 34730774 BACKGROUND

• Li Y, Wei J, Guo W, Sun B, Estillore JP, Wang R, Yoruk A, Roston TM, Sanatani S, Wilde AAM, Gollob MH, Roberts JD, Tseng ZH, Jensen HK, Chen SRW. Human RyR2 (Ryanodine Receptor 2) Loss-of-Function Mutations: Clinical Phenotypes and In Vitro Characterization. Circ Arrhythm Electrophysiol. 2021 Sep;14(9):e010013. doi: 10.1161/CIRCEP.121.010013. Epub 2021 Sep 1.

  PMID: 34546788 BACKGROUND

• Ormerod JOM, Ormondroyd E, Li Y, Taylor J, Wei J, Guo W, Wang R, Sarton CNS, McGuire K, Dreau HMP, Taylor JC, Ginks MR, Rajappan K, Chen SRW, Watkins H. Provocation Testing and Therapeutic Response in a Newly Described Channelopathy: RyR2 Calcium Release Deficiency Syndrome. Circ Genom Precis Med. 2022 Feb;15(1):e003589. doi: 10.1161/CIRCGEN.121.003589. Epub 2021 Dec 24.

  PMID: 34949103 BACKGROUND

• Ni M, Li Y, Wei J, Song Z, Wang H, Yao J, Chen YX, Belke D, Estillore JP, Wang R, Vallmitjana A, Benitez R, Hove-Madsen L, Feng W, Chen J, Roston TM, Sanatani S, Lehman A, Chen SRW. Increased Ca2+ Transient Underlies RyR2-Related Left Ventricular Noncompaction. Circ Res. 2023 Jul 7;133(2):177-192. doi: 10.1161/CIRCRESAHA.123.322504. Epub 2023 Jun 16.

  PMID: 37325910 BACKGROUND

• Ni M, Dadon Z, Ormerod JOM, Saenen J, Hoeksema WF, Antiperovitch P, Tadros R, Christiansen MK, Steinberg C, Arnaud M, Tian S, Sun B, Estillore JP, Wang R, Khan HR, Roston TM, Mazzanti A, Giudicessi JR, Siontis KC, Alak A, Acosta JG, Divakara Menon SM, Tan NS, van der Werf C, Nazer B, Vivekanantham H, Pandya T, Cunningham J, Gula LJ, Wong JA, Amit G, Scheinman MM, Krahn AD, Ackerman MJ, Priori SG, Gollob MH, Healey JS, Sacher F, Nof E, Glikson M, Wilde AAM, Watkins H, Jensen HK, Postema PG, Belhassen B, Chen SRW, Roberts JD. A Clinical Diagnostic Test for Calcium Release Deficiency Syndrome. JAMA. 2024 Jul 16;332(3):204-213. doi: 10.1001/jama.2024.8599.

  PMID: 38900490 BACKGROUND

Study Officials

• Thomas M Roston, MD, PhD

  University of British Columbia

  STUDY CHAIR

• Jason D Roberts, MD MAS

  McMaster University

  PRINCIPAL INVESTIGATOR

• SR Wayne Chen, PhD

  University of Calgary

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jason D Roberts, MD MAS

CONTACT

905-297-3479; crds@phri.ca

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 26 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2024
• First Posted: July 18, 2024
• Study Start: November 21, 2024
• Primary Completion (Estimated): December 31, 2050
• Study Completion (Estimated): December 31, 2050
• Last Updated: February 5, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (3); BE (2); AU (1); DK (1); GB (1); IL (1); FR (1); CA (6)