Study of the Prevalence of Fabry Disease in French Dialysis Patients (FABRYDIAL)

Fabry Disease (FD) is a rare genetic lysosomal storage disease including an X-linked mutation and characterized by an alpha-galactosidase A (GLA) deficiency. It causes globotriaosylceramide (GB3) accumulation within blood vessels, tissues and organs. This accumulation leads to multisystemic deficiency, such as progressive kidney insufficiency. Due to its low prevalence and non-specific symptoms, FD is under-diagnosed. Its estimated incidence is ranged from 1/40,000 to 1/120,000 live births. A review of the international literature suggests a higher prevalence among dialysis patients. Its diagnosis could lead to an enzyme replacement therapy, in order to avoid the occurrence or aggravation of other organs irreversible lesions, and to enhance the familial screening.

We aim to conduct a multicentric cross-sectional prevalence study in 5 areas (Rhône-Alpes-Auvergne, Ile de France, Aquitaine, Picardie and department of Gard), involving biologic collection and genetic diagnosis test. Our objective is to measure the prevalence of FD among dialysis patients. Eligible patients will be included after signing the informed consent.

In the five participating areas, all of the dialysis centers will be asked for involvement. Nominative data of the French renal epidemiology and information network (REIN) registry will enable first patients screening for eligibility among prevalent dialysis patients. If needed (insufficient or absent data in the REIN registry), data will be completed with medical files.

A blood drop will be collected during a hemodialysis session (or the monthly test for peritoneal dialysis treated patients) and deposited on an anonymized blotting paper. For the diagnosis of FD, men will have a measure of the alpha-galactosidase activity, whereas screening in women will be established on the association of alpha-galactosidase activity and lyso-GB3 analysis. If results are compatible with FD, genetic mutation will be search in order to confirm the diagnosis for women, and, for all, to offer familial testing. Results will be transmitted to the nephrologist within the next 2 to 9 weeks. Patients diagnosed with FD will be managed in accordance with the guidelines of the French National Authority for Health (F.N.A.H.).

Study Overview

• Status: Unknown
• Conditions: End Stage Renal Disease; Fabry Disease; Renal Dialysis
• Intervention / Treatment: Biological: Dried blood spot (DBS) sampling

• Study Type: Observational
• Enrollment (Anticipated): 6000

Contacts and Locations

Study Locations

• France
  • Aquitaine
    • Bordeaux, Aquitaine, France, 33000
      • Recruiting
      • Hôpital Pellegrin Tripode, Service de néphrologie-Dialyse, place Amélie Rabat Léon
      • Contact: Valérie De PRECIGOUT, MD; Phone Number: +33 (0)556 795 831; Email: valerie.deprecigout@chu-bordeaux.fr
  • Gard
    • Nîmes, Gard, France, 30029
      • Recruiting
      • Hôpital Universitaire Carémeau, Service de Néphrologie, Place du Pr R. Debré
      • Contact: Olivier MORANNE, Pr; Phone Number: +33 (0)466 683 256; Email: olivier.moranne@chu-nimes.fr
  • Ile de France
    • Paris, Ile de France, France, 75015
      • Recruiting
      • Hôpital Necker, APHP Paris, Service de néphrologie-dialyse, 149 rue de Sèvres
      • Contact: Bertrand KNEBELMANN, Pr; Phone Number: +33 (0)144 495 241; Email: bertrand.knebelmann@nck.aphp.fr
  • Nord Picardie
    • Amiens, Nord Picardie, France, 80054
      • Recruiting
      • CHU d'Amiens, Site Sud, Service de néphrologie, D408
      • Contact: Gabriel CHOUKROUN, Pr; Phone Number: +33 (0)322 455 860; Email: choukroun.gabriel@chu-amiens.fr
  • Rhones Alpes
    • Lyon, Rhones Alpes, France, 69437
      • Recruiting
      • Hospices Civils de Lyon, Hôpital E Herriot, Service de néphrologie, 5 place d'Arsonval
      • Contact: Laurent JUILLARD, Pr; Phone Number: +33 (0)472 110 159; Email: Laurent.juillard@univ-lyon1.fr
      • Contact: Laure GUITTARD; Phone Number: +33 (0)472 112 801; Email: Laure.guittard@chu-lyon.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Population of adult patients undergoing chronic renal dialysis for end stage kidney disease in 5 French areas (Rhône-Alpes-Auvergne, Ile de France, Aquitaine, Picardie and department of Gard)

Description

Inclusion Criteria:

• Woman or men
• Age between 18 to 70 years
• Patient undergoing chronic renal dialysis with a confirmed diagnosis of FD or a diagnosis of nephropathy according to the French renal epidemiology and information network (REIN) registry classification :
• Primitive glomerulonephritis
• Hypertension
• Diabetic nephropathy with non type 1 diabetes
• Vascular nephropathy
• Pyelonephritis
• Unknown or other
• Informed consent signed

Exclusion Criteria:

• IgA nephropathy confirmed by renal biopsy
• Diabetic nephropathy with type 1 diabetes
• Autosomal dominant polycystic kidney disease
• Law-protected patient
• Patient who doesn't belong to the national social security system, or similar system
• Pregnant or lactating woman

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Population of adult patients undergoing chronic renal dialysis; Population of adult patients undergoing chronic renal dialysis for end stage kidney disease in 5 French areas (Rhône-Alpes-Auvergne, Ile de France, Aquitaine, Picardie and department of Gard)

Biological: Dried blood spot (DBS) sampling; DBS be collected during a hemodialysis session and deposited on an anonymized blotting paper. Laboratory ARCHIMED Life Science GmbH, based in Austria will perform all the biological analysis. For the diagnosis, men will have a measure of the alpha-galactosidase activity level, whereas screening in women will be established on the association of alpha-galactosidase activity and lyso-GB3 analyses. If results are compatible, genetic mutation will be searches in order to confirm the diagnosis for women.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of Fabry disease	Analysis for the diagnostic of FD will be performed on blood drops: For men : alpha galactosidase A enzyme activity (positive test if < 1,2µmol/L/h); For women : alpha galactosidase A enzyme activity (positive test if < 1,2µmol/L/h) and lyso-GB3 (positive test if > 6 ng/mL) analysis. If results are compatible, GLA mutation will be confirmed by genotyping.	during a hemodialysis session (Day 1)

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Laurent JUILLARD, Pr, Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start: May 1, 2016
• Primary Completion (ANTICIPATED): May 1, 2017
• Study Completion (ANTICIPATED): May 1, 2017

Study Registration Dates

• First Submitted: July 21, 2016
• First Submitted That Met QC Criteria: July 21, 2016
• First Posted (ESTIMATE): July 25, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): July 25, 2016
• Last Update Submitted That Met QC Criteria: July 21, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Prevalence; End Stage Renal Disease; Fabry disease; chronic dialysis; alpha galactosidase A; Lyso-GB3; GLA mutation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Urologic Diseases; Renal Insufficiency; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Renal Insufficiency, Chronic; 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; Kidney Diseases; Kidney Failure, Chronic; Fabry Disease
• Other Study ID Numbers: 69HCL16_0271