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Prevalence and Characteristics of Fabry Disease (FD) in Patients With Stroke or Small Fiber Neuropathy (FABRY)

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ClinicalTrials.gov Identifier: NCT03230149
Recruitment Status : Recruiting
First Posted : July 26, 2017
Last Update Posted : March 29, 2018
Sponsor:
Collaborator:
Shire International GmbH
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:

FD is pan-ethnic. Its reported annual incidence of 1 in 100,000 may underestimate the true prevalence of the disease. Indeed, recently, in addition with affected males FD developing a "classic" phenotype, " cardiac variant " and " renal variant " have been reported for FD patients with predominant or exclusive cardiac or renal involvement. " Neurologic variant " could exist.

Nervous system can be affect by FD leading to cerebrovascular diseases (ischemic or haemorrhagic strokes, TIA (Transient Ischemic Attacks) or peripheral neuropathy (acroparesthesias and pain).

Aims will be to determine the prevalence of Fabry disease in patients with stroke or small fiber neuropathy, and their characteristics


Condition or disease Intervention/treatment
Fabry Disease Diagnostic Test: Measurements of the alpha-GAL enzyme activity

Detailed Description:

FD is pan-ethnic. Its reported annual incidence of 1 in 100,000 may underestimate the true prevalence of the disease. Indeed, recently, in addition with affected males FD developing a "classic" phenotype, " cardiac variant " and " renal variant " have been reported for FD patients with predominant or exclusive cardiac or renal involvement. " Neurologic variant " could exist.

Nervous system can be affect by FD leading to cerebrovascular diseases (ischemic or haemorrhagic strokes, TIA (Transient Ischemic Attacks) or peripheral neuropathy (acroparesthesias and pain).

  1. Considering strokes, they are the third leading cause of death in France, with more than 140,000 people presenting a stroke per year. Stroke incidence is 1-2/1000 people per year. If the mean age of stroke patient is 72 yo, 25% of them are under 55 yo. The etiology of stroke in young patients remains undetermined in up to half of the cases. Data on prevalence of FD in people with cryptogenic ischaemic stroke are limited and controversial. In addition to cryptogenic strokes, FD can lead to stroke from arterial or heart diseases (secondary to high blood pressure, renal insufficiency, cardiomyopathy, rate variability, arrhythmias, valvular insufficiency).

    The investigators aimed to evaluate the frequency of FD in a cohort of stroke patients in tertiary stroke centers in consecutively recruited patients under 60 yo. The investigators will include patients with so-called cryptogenic stroke but also stroke patients due to large artery atherosclerosis, cardioembolism, and small-vessel occlusion. The investigators will also study the clinical and radiological characteristic of stroke patients due to FD, and will compare these data with those from patients without FD, supported by biochemical and genetic findings.

  2. Considering peripheral nervous system, Small fiber neuropathy (SFN) is a subgroup of peripheral neuropathy which is characterized by an affection of the thin myelinated A-δ and unmyelinated C-fibers. SFN patients present with sensory symptoms and pain. SFN are not a rare condition; recent study showed a minimum prevalence of 50/100.000. The most commonly etiology reported for SFN is diabetes mellitus ; Other possible etiologies include connective tissue disease, celiac disease, thyroid dysfunction, vitamin B12 deficiency, monoclonal gammopathy, HIV and hepatitis C infections, amyloidosis, toxicity due to alcohol or drugs, and hereditary neuropathies including FD, suspected to be underdiagnosed.

In SFN patients,the investigators aimed to screen for FD in our tertiary national center for peripheral neuropathies, in addition to others diseases or affections, to evaluate the frequency of FD in a large cohort of SFN patients, and describe the clinical phenotype of SFN in FD patients compared to other ones.


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Study Type : Observational
Estimated Enrollment : 1100 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Prevalence and Characteristics of Fabry Disease (FD) in Patients With Stroke or Small Fiber Neuropathy
Actual Study Start Date : March 12, 2018
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : March 2020


Group/Cohort Intervention/treatment
Molecular and genetic tests
Measurements of the alpha-GAL enzyme activity will be performed knowing that for male patients with alpha-GAL activities below the cut-off value and all female patients, a blood sampling for full genetic sequencing of all seven exons including promotors of the a-GAL gene will be done
Diagnostic Test: Measurements of the alpha-GAL enzyme activity
Blotting paper blood tests in order to highlight an enzyme deficiency for hemizygous males with DBS kits in order to detect Fabry disease, with genetic confirmation if an abnormality is detected. For women genotyping is mandatory.




Primary Outcome Measures :
  1. frequency of FD in a cohort of stroke patients [ Time Frame: at the end of the study (an average of 2 years) ]
    number of patients with fabry disease in the cohort of stroke patients (1000 patients)


Secondary Outcome Measures :
  1. frequency of FD in a cohort of Small fiber neuropathy (SFN) patients [ Time Frame: at the end of the study (an average of 2 years) ]
    number of patients with fabry disease in the cohort of small fiber neuropathy patients (100 patients)



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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients between 18 and 60 years old diagnosed with a TIA/ strocke or a SFN
Criteria

Inclusion Criteria:

  • patient over 18 yo and under 60 yo
  • diagnosed with a TIA / stroke (ischemic and haemorrhagic strokes) based on clinical evaluation and MRI
  • diagnosed with small fibers neuropathy (SFN) with normal nerve conduction studies in conventional electrophysiology

Exclusion Criteria:

  • patients over 60 yo

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03230149


Contacts
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Contact: Christian DENIER, Pr +33145212618 christian.denier@aphp.fr
Contact: Didier SMADJA, Pr +331 61 69 52 00 didier.smadja@ch-sud-francilien.fr

Locations
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France
CHU de Bicêtre, UNSIV (neurovascular stroke unit) Recruiting
Le Kremlin Bicêtre, France, 94270
Contact: Christan DENIER, Pr    +33145212618    christian.denier@aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Shire International GmbH

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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT03230149     History of Changes
Other Study ID Numbers: HAO16026
First Posted: July 26, 2017    Key Record Dates
Last Update Posted: March 29, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Fabry
Stroke
Cerebrovascular Accident
small fiber neuropathy

Additional relevant MeSH terms:
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Fabry Disease
Small Fiber Neuropathy
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
Metabolism, Inborn Errors
Lipidoses
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders
Peripheral Nervous System Diseases
Neuromuscular Diseases