Long Duration Holter ECG in Fabry Disease

Natural History of Cardiac Rhythm and Conduction Disorders in Patients With Fabry Disease Evaluated by Long-Term Implantable Holter ECG

The main objective is to assess the occurrence of cardiac arrhythmias and conduction disorders during a three-year follow-up using implantable Holter ECG monitoring in 40 patients with Fabry disease. The secondary objectives are to analyze the correlations of these anomalies with changes in cardiac MRI and echocardiographic parameters as biological parameters and overall severity of the disease assessed by MSSI.

Study Overview

• Status: Not yet recruiting
• Conditions: Fabry Disease
• Intervention / Treatment: Diagnostic test: Implantation (subcutaneous) of a marketed miniaturized Holter ECG recording device

Detailed Description

The main objective of this non-blinded, monocentric non-randomized study is to assess the occurrence of cardiac arrhythmias and conduction disorders (sinus dysfunction, branch block [BB], atrioventricular block [BAV], sustained [TVS] or non-supported [TVNS] ventricular tachycardias, atrial fibrillation [AF] during a three-year follow-up in 40 patients with Fabry disease (half with left ventricular hypertrophy) using an implantable Holter ECG device (Medtronic Reveal-LINQ™). The secondary objectives are to analyze the correlations (at 1, 2 and 3 years) of these anomalies with the modifications of :

• cardiac MRI [Magnetic Resonance Imaging] data at inclusion [M0] and at 36 months [M36] (left ventricular hypertrophy [HVG], amplitude of the T1 signal, extent of fibrosis); MRIs will be performed before implantation and after removal of the Holter to avoid the reading artifacts linked to the device.
• echocardiographic measurements of the left ventricle (overall longitudinal strain systolic [SGL] and ejection fraction [FE])
• biological parameters (BNP or NT-proBNP, ultra-sensitive troponin and Lyso-Gb3)
• the overall severity of the disease assessed by MSSI (Mainz Severity Score Index), DFG and proteinuria

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male patient
• Age greater than or equal to 18 years on the day of inclusion
• Presence of a morbid mutation for MF
• Signature of the informed consent form
• Absence of significant valve disease, verified on medical file (absence stenosis or regurgitation <2+ in color Doppler on a scale 1 to 4+ by extension of the jet)
• No history of known or documented myocardial infarction nor CAD
• No pacemaker or ICD
• no history of AF, NSVT, high-degree AV block
• Correct echogenicity
• No treatment by corticosteroid or immunosuppressive drugs
• creatinine clearance >/= 30 Ml/mn
• LVEF ≥ 50% by ultrasound and / or MRI
• No contraindication to MRI (or claustrophobia) and gadolinium injection
• Affiliation to the French social security insurance

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: ONE; One single group of patients	Diagnostic test: Implantation (subcutaneous) of a marketed miniaturized Holter ECG recording device; Subcutaneously implanted under local anesthesia of the device on the presternal or subclavicular region

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Occurrence of cardiac arrhythmias and conduction disorders	3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Correlations between electrical disorders and changes in MRI/ultrasonic data (LV mass, T1 signal, fibrosis extent , systolic strain, ejection fraction), concentrations of BNP, troponin, Lyso-Gb3, MSSI score and renal function	3 years

Collaborators and Investigators

• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2020
• Primary Completion (Anticipated): September 1, 2025
• Study Completion (Anticipated): September 1, 2025

Study Registration Dates

• First Submitted: June 12, 2020
• First Submitted That Met QC Criteria: June 18, 2020
• First Posted (Actual): June 19, 2020

Study Record Updates

• Last Update Posted (Actual): June 19, 2020
• Last Update Submitted That Met QC Criteria: June 18, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Cerebral Small Vessel Diseases; Lipidoses; Lipid Metabolism, Inborn Errors; Fabry Disease
• Other Study ID Numbers: C19-57

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