Study of the Relation Between Lipid Myocardial Overload Evaluated by Cardiac Magnetic Resonance Imaging (MRI), Alteration of Longitudinal Myocardial Deformations by Echocardiography, and Clinical Achievements (Functional, Biological and Electrical) in Fabry Disease, and Its Outcomes.

• Conditions: Fabry Disease
• Interventions: Diagnostic Test: Echocardiography at T0; Diagnostic Test: Exercise test; Device: MRI without contrast agent injection; Biological: Biological assays; Device: MRI with contrast agent injection; Diagnostic Test: Echocardiography at M24

• Registration Number: NCT03123523
• Lead Sponsor: University Hospital, Bordeaux

Brief Summary

Anderson-Fabry disease is a genetic lysosomal storage disease, linked to chromosome X (gene GLA), responsible of enzyme synthesis deficit in α-galactosidase A with intracellular sphingolipids accumulation and multiorganic achievement.

If renal complication is principally responsible of the pejorative evolution of the disease, it may also exist a cardiac achievement, symptomatic or not (heart failure symptoms including dyspnea, conduction abnormalities, supra-ventricular and ventricular arrhythmias), with or without left ventricular hypertrophy (LVH).

Administration of agalsidase-α or ß, a genetic engineering synthetic equivalent of the deficient enzyme, should significantly slow disease evolution indeed reduce LVH.

Some patients with Fabry disease without LVH should present, compared to healthy subjects, indirect early markers of intramyocyte lipid overload:

* in echocardiography, longitudinal myocardial deformation (strain) should be altered while ejection fraction is preserved, and

* in cardiac MRI, T1 mapping should be reduced1. This was also previously demonstrated in Fabry patients with LVH2. However, are these abnormalities of longitudinal deformation in echocardiography and of T1 mapping in MRI correlated to the presence of pejorative cardiac markers (such as clinical and functional tolerances, Brain Natriuretic Peptide (BNP) level and electrical complications)?

Detailed Description

Not available

Study Timeline

• Study Start: 2016-10-18
• Status Verified: 2017-04
• Study First Submitted: 2017-04-12
• Study First Submitted QC: 2017-04-18
• Last Update Submitted: 2017-04-18
• Study First Posted: 2017-04-21
• Last Update Posted: 2017-04-21
• Primary Completion: 2020-04-18
• Study Completion: 2020-04-18

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 55

Inclusion Criteria

Patients group :

• Adults (age ≥18 years), male and female.
• Patients diagnosed genetically having Fabry disease, with or without clinical cardiac symptoms and with different evolution stades of the disease.
• For female in age of procreation, efficient contraception will be required and a negative pregnancy test.
• Oral agreement of the patient after having read information note.
• Patient affiliated to social national Security registry.

Healthy volunteers group:

• Adults (age ≥18 years), male and female.
• Unscathed of cardiovascular pathologies and cardiovascular risk factors.
• For female in age of procreation, efficient contraception will be required and a negative pregnancy test.
• Oral agreement of the patient after having read information note.
• Patient affiliated to social national Security registry.

Exclusion Criteria

For the 2 groups :

• Extracardiac pathology limiting life expectancy <1 year (cancer).
• Pregnant or breastfeeding female.
• Claustrophobia.
• Mechanical prosthetic valve.
• Severe obesity > 140 kg
• Patients with intracardiac device (implantable cardiac defibrillator, pace maker, resynchronisation), surgical clips not MRI compatible, neurosensorial stimulators, cochlear implants, ferromagnetic foreign bodies (ocular, cerebral), neurosurgical derivation valves)
• Impossibility to provide consent or refusal to sign the consent form.

For the patients:

• Previous history of hypersensitivity to gadolinium.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients group	Echocardiography at T0	35 patients
Patients group	Echocardiography at M24	35 patients
Healthy volunteers	Echocardiography at T0	20 healthy volunteers
Patients group	Biological assays	35 patients
Patients group	MRI with contrast agent injection	35 patients
Patients group	Exercise test	35 patients
Healthy volunteers	MRI without contrast agent injection	20 healthy volunteers

Primary Outcome Measures

Name	Time	Method
Metabolic exercise test marker : poor blood pressure adaptation to exercise	Baseline
Metabolic exercise test marker: max level achieved	Baseline
Metabolic exercise test marker : percentage of theoretical maximal heart rate	Baseline
Cardiovascular symptoms	Baseline	Dyspnea, angor, syncope and lipothymia, palpitations, heart failure signs
Biological marker : BNP elevation	Baseline
Metabolic exercise test marker : peak of Oxygen uptake (VO2)	Baseline
Electrical markers at ECG and Holter ECG	Baseline	Measure of conduction troubles; supra-ventricular and ventricular arrhythmias.
Metabolic exercise test marker : percentage of expected peak VO2	Baseline
Metabolic exercise test marker : Expiratory volume / carbon dioxide production (VE/VCO2)	Baseline

Trial Locations

Locations (1)

CHU de Bordeaux; 🇫🇷 Pessac, France