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.

NCT03123523 | Unknown

• 1 other identifier: CHUBX 2016/08
• Study Type: observational
• Target: 55
• Locations: 1 country
• Sites: 1

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)?

Conditions

Fabry Disease

Outcome Measures

Primary Outcomes (9)

• 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

Study Arms (2)

Patients group

35 patients

Diagnostic Test: Echocardiography at T0; Diagnostic Test: Exercise test; Biological: Biological assays; Device: MRI with contrast agent injection; Diagnostic Test: Echocardiography at M24

Healthy volunteers

20 healthy volunteers

Diagnostic Test: Echocardiography at T0; Device: MRI without contrast agent injection

Interventions

Echocardiography at T0 DIAGNOSTIC_TEST

Healthy volunteers; Patients group

Exercise test DIAGNOSTIC_TEST

Patients group

Biological assays BIOLOGICAL

Creatinin, hematocrit and BNP assays

Patients group

MRI with contrast agent injection DEVICE

With injection of gadolinium

Patients group

MRI without contrast agent injection DEVICE

Without injection of gadolinium

Healthy volunteers

Echocardiography at M24 DIAGNOSTIC_TEST

Patients group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospital, Bordeaux: lead

Study Sites (1)

CHU de Bordeaux

Pessac, 33604, France

RECRUITING

MeSH Terms

Conditions

Fabry Disease

Interventions

Exercise Test; Biological Assay

Condition Hierarchy (Ancestors)

Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Intervention Hierarchy (Ancestors)

Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Respiratory Function Tests; Diagnostic Techniques, Respiratory System; Ergometry; Investigative Techniques

Central Study Contacts

Réant patricia, MD

CONTACT

(0)5 57 65 64 85; patricia.reant@chu-bordeaux.fr

Carpentier Céline

CONTACT

(0)5 57 65 61 68; celine.carpentier@chu-bordeaux.fr

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2017
• First Posted: April 21, 2017
• Study Start: October 18, 2016
• Primary Completion: April 18, 2020
• Study Completion: April 18, 2020
• Last Updated: April 21, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)