<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03230149</url>
  </required_header>
  <id_info>
    <org_study_id>HAO16026</org_study_id>
    <nct_id>NCT03230149</nct_id>
  </id_info>
  <brief_title>Prevalence and Characteristics of Fabry Disease (FD) in Patients With Stroke or Small Fiber Neuropathy</brief_title>
  <acronym>FABRY</acronym>
  <official_title>Prevalence and Characteristics of Fabry Disease (FD) in Patients With Stroke or Small Fiber Neuropathy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Shire International GmbH</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      FD is pan-ethnic. Its reported annual incidence of 1 in 100,000 may underestimate the true&#xD;
      prevalence of the disease. Indeed, recently, in addition with affected males FD developing a&#xD;
      &quot;classic&quot; phenotype, &quot; cardiac variant &quot; and &quot; renal variant &quot; have been reported for FD&#xD;
      patients with predominant or exclusive cardiac or renal involvement. &quot; Neurologic variant &quot;&#xD;
      could exist.&#xD;
&#xD;
      Nervous system can be affect by FD leading to cerebrovascular diseases (ischemic or&#xD;
      haemorrhagic strokes, TIA (Transient Ischemic Attacks) or peripheral neuropathy&#xD;
      (acroparesthesias and pain).&#xD;
&#xD;
      Aims will be to determine the prevalence of Fabry disease in patients with stroke or small&#xD;
      fiber neuropathy, and their characteristics&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      FD is pan-ethnic. Its reported annual incidence of 1 in 100,000 may underestimate the true&#xD;
      prevalence of the disease. Indeed, recently, in addition with affected males FD developing a&#xD;
      &quot;classic&quot; phenotype, &quot; cardiac variant &quot; and &quot; renal variant &quot; have been reported for FD&#xD;
      patients with predominant or exclusive cardiac or renal involvement. &quot; Neurologic variant &quot;&#xD;
      could exist.&#xD;
&#xD;
      Nervous system can be affect by FD leading to cerebrovascular diseases (ischemic or&#xD;
      haemorrhagic strokes, TIA (Transient Ischemic Attacks) or peripheral neuropathy&#xD;
      (acroparesthesias and pain).&#xD;
&#xD;
        1. Considering strokes, they are the third leading cause of death in France, with more than&#xD;
           140,000 people presenting a stroke per year. Stroke incidence is 1-2/1000 people per&#xD;
           year. If the mean age of stroke patient is 72 yo, 25% of them are under 55 yo. The&#xD;
           etiology of stroke in young patients remains undetermined in up to half of the cases.&#xD;
           Data on prevalence of FD in people with cryptogenic ischaemic stroke are limited and&#xD;
           controversial. In addition to cryptogenic strokes, FD can lead to stroke from arterial&#xD;
           or heart diseases (secondary to high blood pressure, renal insufficiency,&#xD;
           cardiomyopathy, rate variability, arrhythmias, valvular insufficiency).&#xD;
&#xD;
           The investigators aimed to evaluate the frequency of FD in a cohort of stroke patients&#xD;
           in tertiary stroke centers in consecutively recruited patients under 60 yo. The&#xD;
           investigators will include patients with so-called cryptogenic stroke but also stroke&#xD;
           patients due to large artery atherosclerosis, cardioembolism, and small-vessel&#xD;
           occlusion. The investigators will also study the clinical and radiological&#xD;
           characteristic of stroke patients due to FD, and will compare these data with those from&#xD;
           patients without FD, supported by biochemical and genetic findings.&#xD;
&#xD;
        2. Considering peripheral nervous system, Small fiber neuropathy (SFN) is a subgroup of&#xD;
           peripheral neuropathy which is characterized by an affection of the thin myelinated A-δ&#xD;
           and unmyelinated C-fibers. SFN patients present with sensory symptoms and pain. SFN are&#xD;
           not a rare condition; recent study showed a minimum prevalence of 50/100.000. The most&#xD;
           commonly etiology reported for SFN is diabetes mellitus ; Other possible etiologies&#xD;
           include connective tissue disease, celiac disease, thyroid dysfunction, vitamin B12&#xD;
           deficiency, monoclonal gammopathy, HIV and hepatitis C infections, amyloidosis, toxicity&#xD;
           due to alcohol or drugs, and hereditary neuropathies including FD, suspected to be&#xD;
           underdiagnosed.&#xD;
&#xD;
      In SFN patients,the investigators aimed to screen for FD in our tertiary national center for&#xD;
      peripheral neuropathies, in addition to others diseases or affections, to evaluate the&#xD;
      frequency of FD in a large cohort of SFN patients, and describe the clinical phenotype of SFN&#xD;
      in FD patients compared to other ones.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 12, 2018</start_date>
  <completion_date type="Actual">December 24, 2021</completion_date>
  <primary_completion_date type="Actual">December 24, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>frequency of FD in a cohort of stroke patients</measure>
    <time_frame>at the end of the study (an average of 2 years)</time_frame>
    <description>number of patients with fabry disease in the cohort of stroke patients (1000 patients)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>frequency of FD in a cohort of Small fiber neuropathy (SFN) patients</measure>
    <time_frame>at the end of the study (an average of 2 years)</time_frame>
    <description>number of patients with fabry disease in the cohort of small fiber neuropathy patients (100 patients)</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">379</enrollment>
  <condition>Fabry Disease</condition>
  <arm_group>
    <arm_group_label>Molecular and genetic tests</arm_group_label>
    <description>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</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Measurements of the alpha-GAL enzyme activity</intervention_name>
    <description>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.</description>
    <arm_group_label>Molecular and genetic tests</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients between 18 and 60 years old diagnosed with a TIA/ strocke or a SFN&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  patient over 18 yo and under 60 yo&#xD;
&#xD;
          -  diagnosed with a TIA / stroke (ischemic and haemorrhagic strokes) based on clinical&#xD;
             evaluation and MRI&#xD;
&#xD;
          -  diagnosed with small fibers neuropathy (SFN) with normal nerve conduction studies in&#xD;
             conventional electrophysiology&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  patients over 60 yo&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>CHU de Bicêtre, UNSIV (neurovascular stroke unit)</name>
      <address>
        <city>Le Kremlin Bicêtre</city>
        <zip>94270</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>July 24, 2017</study_first_submitted>
  <study_first_submitted_qc>July 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 26, 2017</study_first_posted>
  <last_update_submitted>September 6, 2022</last_update_submitted>
  <last_update_submitted_qc>September 6, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 7, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Fabry</keyword>
  <keyword>Stroke</keyword>
  <keyword>Cerebrovascular Accident</keyword>
  <keyword>small fiber neuropathy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fabry Disease</mesh_term>
    <mesh_term>Small Fiber Neuropathy</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03230149
org study id: HAO16026
nct id: NCT03230149
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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
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.
observational model: Case-Only
time perspective: Prospective
measure: frequency of FD in a cohort of stroke patients
time frame: at the end of the study (an average of 2 years)
description: number of patients with fabry disease in the cohort of stroke patients (1000 patients)
measure: 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)
description: number of patients with fabry disease in the cohort of small fiber neuropathy patients (100 patients)
arm group label: Molecular and genetic tests
description: 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
intervention type: Diagnostic Test
intervention name: Measurements of the alpha-GAL enzyme activity
description: 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.
arm group label: Molecular and genetic tests
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
facility: 
country: France
responsible party type: Sponsor
mesh term: Fabry Disease
mesh term: Small Fiber Neuropathy
sharing ipd: No