Recruiting

CRDSEvaluation of A Clinical Diagnostic Test for CRDS

Sponsor:

Population Health Research Institute

Code:

NCT06188689

Conditions

Calcium Release Deficiency Syndrome (CRDS)

Eligibility Criteria

Sex: All

Age: 0+

Healthy Volunteers: Not accepted

Interventions

Pacing

Study Details

Brief summary:

Calcium Release Deficiency Syndrome (CRDS) is a novel inherited arrhythmia syndrome secondary to RyR2 loss-of-function that confers a risk of sudden cardiac death. Diagnosis of CRDS presently requires cellular-based in vitro confirmation that an RyR2 variant causes loss-of-function. We hypothesize that CRDS can be diagnosed clinically through evaluation of the repolarization response to brief tachycardia, mediated by cardiac pacing, and a subsequent pause.

Conditions

Calcium Release Deficiency Syndrome (CRDS)

Study ID

NCT06188689

Start date

Feb 2, 2023

Status verified date

May, 2026

Completion date

Mar, 2028

Anticipated

Primary completion date

Dec, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 0+

Healthy Volunteers: Not accepted

Cohort 1: Calcium Release Deficiency Syndrome (CRDS) Cases

Inclusion criteria:

• Presence of an RyR2 variant confirmed to be loss-of-function on in vitro testing

Exclusion criteria:

• Unable to provide informed consent

Cohort 2: Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) Cases

Inclusion criteria:

Satisfy a clinical phenotype consistent with the Expert Consensus Statement
Presence of a confirmed or presumed pathogenic gain-of-function RyR2 variant OR homozygous or compound heterozygous for likely pathogenic/pathogenic CASQ2 variants

Exclusion criteria:

Unable to provide informed consent
Use of a QT prolonging medication, aside from flecainide, at the time of the burst pacing maneuvers

Cohort 3: Survivors of Unexplained Cardiac Arrest (UCA)

Inclusion criteria:

Cardiac arrest requiring cardioversion or defibrillation that remains unexplained following an ECG, echocardiogram, coronary assessment, cardiac MRI, and exercise treadmill test
Undergone genetic testing that includes screening of RyR2\*

Exclusion criteria:

Unable to provide informed consent
Use of a QT prolonging medication at the time of the burst pacing maneuvers

Among survivors of UCA that possess a rare RyR2 variant in the absence of a CPVT phenotype, in vitro functional testing will be performed in order to confirm it is not loss- or gain-of-function (and will be arranged through the laboratory of Dr. Wayne Chen at the University of Calgary).

Cohort 4: SVT controls

Inclusion criteria:

• Undergoing an invasive electrophysiology study

Exclusion criteria:

Ventricular cardiomyopathy
Ventricular pre-excitation
Long QT syndrome
Use of a QT prolonging medication at the time of the EP study
Use of a Class I or Class III anti-arrhythmic drug at the time of the EP study
Known obstructive coronary artery disease (existing coronary stenosis >50%)
Unable to provide informed consent

Study Design

Enrollment

400 participants

Anticipated

Intervention Model

Single group

Primary purpose

Diagnostic

Interventions and Outcome Measures

Arms

experimental: Pacing

Separate ventricular and atrial pacing trains will be administered at different cycle lengths and the ventricular repolarization response on the first sinus beat following the subsequent pause will be evaluated.

Interventions

Pacing

1. Ventricular 10 beat burst at 500ms (120bpm)
2. Ventricular 10 beat burst at 400ms (150bpm)
3. Atrial 10 beat burst at 500ms (120bpm)
4. Atrial 10 beat burst at 400ms (150bpm).

Primary outcome measure

ΔT-wave amplitude value [ Time Frame: At time of pacing maneuver ]
ΔQT value [ Time Frame: At time of pacing maneuver ]

Central Contacts and Locations

Central contacts

Jason Roberts, MD MAS

905-297-3479 jason.roberts@phri.ca

Locations

University of California

Recruiting

San Francisco, California, United States, 94143

Contacts

Project Manager

905-521-2100 crds@phri.ca

Principal Investigator:

Vasanth Vedantham, MD, PhD

Boston Children's Hospital

Recruiting

Boston, Massachusetts, United States, 02115

Contacts

Project Manager

905-521-2100 crds@phri.ca

Principal Investigator:

Dominic Abrams, MBBS, MD, MBA

Mayo Clinic

Recruiting

Rochester, Minnesota, United States, 55905

Contacts

Project Manager

905-521-2100 crds@phri.ca

Principal Investigator:

John Giudicessi, MD, PhD

University of Washington

Recruiting

Seattle, Washington, United States, 98195

Contacts

Project Manager

905-521-2100 crds@phri.ca

Principal Investigator:

Uyanga Batnyam, MD

University of Calgary

Recruiting

Calgary, Alberta, Canada, T2N 1N4

Contacts

Project Manager

905-521-2100 crds@phri.ca

Principal Investigator:

Erkan Ilhan, MD

Alberta Health Services

Recruiting

Edmonton, Alberta, Canada, T6G 2C8

Contacts

Project Manager

905-521-2100 crds@phri.ca

Principal Investigator:

Joseph Atallah, MD CM, MSc

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

Recruiting

Vancouver, British Columbia, Canada, V6H 3N1

Contacts

Project Manager

905-521-2100 crds@phri.ca

Principal Investigator:

Shubhayan Sanatani, MD

The University of British Columbia

Recruiting

Vancouver, British Columbia, Canada, V6T 1Z3

Contacts

Project Manager

905-521-2100 crds@phri.ca

Principal Investigator:

Thomas M Roston, MD

Hamilton General Hospital

Recruiting

Hamilton, Ontario, Canada, L8L 2X2

Contacts

Project Manager

905-521-2100 crds@phri.ca

Principal Investigator:

Jason D Roberts, MD MAS

London Health Sciences Centre - University Hospital

Recruiting

London, Ontario, Canada, N6A 5A5

Contacts

Project Manager

905-521-2100 crds@phri.ca

Principal Investigator:

Habib R Khan, MD

Ottawa Heart Institute

Recruiting

Ottawa, Ontario, Canada, K1Y 4W7

Contacts

Project Manager

905-521-2100 crds@phri.ca

Principal Investigator:

Simon Hansom, MD

Toronto General Hospital

Recruiting

Toronto, Ontario, Canada, M5G 2C4

Contacts

Project Manager

905-521-2100 crds@phri.ca

Principal Investigator:

Michael H. Gollob, MD, FRCP(C)

Montréal Heart Institute

Recruiting

Montreal, Quebec, Canada, H1T 1C8

Contacts

Project Manager

905-521-2100 crds@phri.ca

Principal Investigator:

Rafik Tadros, MD PhD

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

Recruiting

Québec, Quebec, Canada, G1V 4G5

Contacts

Project Manager

905-521-2100 crds@phri.ca

Principal Investigator:

Christian Steinberg, MD

More Information

Sponsor

Population Health Research Institute

Last update posted

Jul 22, 2026

Last verified

May, 2026

Keywords

cardiac arrhythmia, sudden cardiac death, cardiac ryanodine receptor, unexplained cardiac arrest

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Population Health Research Institute on 2026-07-22.