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. (FABRY-Image)

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)?

Study Overview

• Status: Unknown
• Conditions: Fabry Disease
• Intervention / Treatment: Diagnostic test: Echocardiography at T0; Diagnostic test: Exercise test; Biological: Biological assays; Device: MRI with contrast agent injection; Diagnostic test: Echocardiography at M24; Device: MRI without contrast agent injection

• Study Type: Observational
• Enrollment (Anticipated): 55

Contacts and Locations

• Study Contact: Name: Réant Patricia, MD; Phone Number: +33 (0)5 57 65 64 85; Email: patricia.reant@chu-bordeaux.fr
• Study Contact Backup: Name: Carpentier Céline; Phone Number: +33 (0)5 57 65 61 68; Email: celine.carpentier@chu-bordeaux.fr

Study Locations

• France
  • Pessac, France, 33604
    • Recruiting
    • CHU de Bordeaux
    • Contact: Réant Patricia, MD; Phone Number: +33 (0)5 57 65 64 85; Email: patricia.reant@chu-bordeaux.fr
    • Contact: Carpentier Céline; Phone Number: +33 (0)5 57 65 61 68; Email: celine.carpentier@chu-bordeaux.fr
    • Principal Investigator: Réant Patricia, MD
    • Sub-Investigator: Lafitte Stéphane, MD PhD
    • Sub-Investigator: Reynaud Amélie, MD
    • Sub-Investigator: Cornolle Claire, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

- The 35 patients will be selected from Dr Réant (Cardiologist) and Dr Rooryck-Thambo's (Genetician) consultations, co-responsible of the Regional Competence Centre in Inherited Cardiomyopathies (Bordeaux, france) and from a medical specialized group following regularly these patients (Dr Valérie de Précigout in Nephrology at Bordeaux Pellegrin Hospital, Pr Cyril Goizet and Pr Didier Lacombe in Genetics at Bordeaux Pellegrin Hospital).

Inclusion will be performed according to current management and follow-up recommendations.

- The 20 healthy volunteers will be recruited form a local database (" HSync Study " of Dr Cornolle). Their consent will be requested at inclusion.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients group; 35 patients	Diagnostic test: Echocardiography at T0; Diagnostic test: Exercise test; Biological: Biological assays; Creatinin, hematocrit and BNP assays; Device: MRI with contrast agent injection; With injection of gadolinium; Diagnostic test: Echocardiography at M24
Healthy volunteers; 20 healthy volunteers	Diagnostic test: Echocardiography at T0; Device: MRI without contrast agent injection; Without injection of gadolinium

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiovascular symptoms	Dyspnea, angor, syncope and lipothymia, palpitations, heart failure signs	Baseline
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
Metabolic exercise test marker : peak of Oxygen uptake (VO2)		Baseline
Metabolic exercise test marker : percentage of expected peak VO2		Baseline
Metabolic exercise test marker : Expiratory volume / carbon dioxide production (VE/VCO2)		Baseline
Biological marker : BNP elevation		Baseline
Electrical markers at ECG and Holter ECG	Measure of conduction troubles; supra-ventricular and ventricular arrhythmias.	Baseline

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 18, 2016
• Primary Completion (ANTICIPATED): April 18, 2020
• Study Completion (ANTICIPATED): April 18, 2020

Study Registration Dates

• First Submitted: April 12, 2017
• First Submitted That Met QC Criteria: April 18, 2017
• First Posted (ACTUAL): April 21, 2017

Study Record Updates

• Last Update Posted (ACTUAL): April 21, 2017
• Last Update Submitted That Met QC Criteria: April 18, 2017
• Last Verified: April 1, 2017

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: CHUBX 2016/08

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