<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/NCT01705626</url>
  </required_header>
  <id_info>
    <org_study_id>TRAP 08-2012</org_study_id>
    <nct_id>NCT01705626</nct_id>
  </id_info>
  <brief_title>Screening for the Transthyretin-Related Familial Amyloidotic Polyneuropathy (TTR FAP)</brief_title>
  <acronym>TRAP2-1</acronym>
  <official_title>Screening for the Transthyretin-Related Familial Amyloidotic Polyneuropathy (TTR-FAP): An International, Multicenter, Epidemiological Protocol</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>CENTOGENE GmbH Rostock</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>CENTOGENE GmbH Rostock</source>
  <oversight_info>
    <has_dmc>Yes</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>
      An International, multicenter, epidemiological observational study investigating the&#xD;
      prevalence of Transthyretin-Related Familial Amyloidotic Polyneuropathy (TTR-FAP) in&#xD;
      participants with small fiber polyneuropathy of no obvious etiology.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Transthyretin-related Familial Amyloid Polyneuropathy (TTR-FAP) is an autosomal dominant,&#xD;
      progressive neurodegenerative disease, with fatal outcome occurring within ten years after&#xD;
      onset. Familial amyloid polyneuropathy (FAP) associated with mutations in the transthyretin&#xD;
      (TTR) gene is the most common form of genetic amyloidosis. It accounts several thousand cases&#xD;
      worldwide, with Val30Met mutation identified in most patients and with endemic foci in&#xD;
      Portugal, Sweden and Japan.&#xD;
&#xD;
      TTR FAP is caused by the systemic deposition of amyloidogenic variants of the transthyretin&#xD;
      protein ((Ttr) in the extra-cellular space of tissues and result in disruption of organ&#xD;
      function.The typical presentation of TTR-FAP is a progressive sensory-motor polyneuropathy,&#xD;
      which usually begins with loss of thermal and pain sensation in the feet, slowly ascends up&#xD;
      the limbs and is associated with variable autonomic disturbances and extra-neurological&#xD;
      manifestations (especially a cardiomyopathy).&#xD;
&#xD;
      The goal of the TRAP2.1 Study is to investigate the prevalence of Transthyretin-Related&#xD;
      Familial Amyloidotic Polyneuropathy (TTR-FAP) in a cohort of 500 subjects with small fiber&#xD;
      polyneuropathy of no obvious etiology, based on the subject's clinical presentation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 2016</start_date>
  <completion_date type="Actual">May 27, 2022</completion_date>
  <primary_completion_date type="Actual">May 27, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Epidemiological analysis of prevalence of the TTR FAP in participants with small fiber polyneuropathy of no obvious etiology.</measure>
    <time_frame>3 years</time_frame>
    <description>Dry Blood Spot (DBS) samples will be genetically validated via combination of Next-Generation Sequencing (the mutation will be confirmed by Sanger sequencing) and the Multiplex ligation-dependent probe amplification (MLPA) of TTR gene</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Establishment of a biomarker in TTR-positive cohort</measure>
    <time_frame>3 years</time_frame>
    <description>Samples carrying a mutation in the TTR gene will be biochemically analyzed via liquid chromatography multiple reaction monitoring MS and compared with a merged control cohort, in order to establish TTR mutation-specific biomarker/s.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">500</enrollment>
  <condition>Polyneuropathy, Amyloid</condition>
  <condition>Neuropathic Pain</condition>
  <condition>Cardiac Failure</condition>
  <condition>Orthostatic Hypotension</condition>
  <condition>Gastrointestinal Disorders</condition>
  <arm_group>
    <arm_group_label>Participants diagnosed with small fiber polyneuropathy no obvious etiology</arm_group_label>
    <description>Participants aged between 18 and 85 years, diagnosed with small fiber polyneuropathy of no obvious etiology, without diagnosis of alcoholism and not undergoing chemotherapy for cancer</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood sample applied on the Dry Blood Spot (DBS) Filtercard (Centocard®)&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Participants diagnosed with small fiber polyneuropathy of no obvious etiology.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Informed consent is obtained from the participant&#xD;
&#xD;
          -  The participant is aged between 18 and 85 years of age&#xD;
&#xD;
          -  The participant is diagnosed with small fiber polyneuropathy of no obvious etiology&#xD;
&#xD;
          -  The participant has no diagnosis of alcoholism, according to International Guidelines&#xD;
&#xD;
          -  The participant has not undergone chemotherapy for carcinoma&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inability to provide informed consent&#xD;
&#xD;
          -  The participant is younger than 18 years or older than 85 years of age&#xD;
&#xD;
          -  The etiology of the small fiber polyneuropathy is clearly determined&#xD;
&#xD;
          -  The participant has a diagnosis of alcoholism, according to International Guidelines&#xD;
&#xD;
          -  The participant has undergone chemotherapy for carcinoma&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Peter Bauer, Prof.</last_name>
    <role>Study Chair</role>
    <affiliation>Centogene GmgH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Klinikum Wels-Grieskirchen GmbH, Abteilung für Neurologie</name>
      <address>
        <city>Wels</city>
        <zip>4600</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pécs, Department of Neurology</name>
      <address>
        <city>Pécs</city>
        <zip>7624</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Szeged, Department of Neurology</name>
      <address>
        <city>Szeged</city>
        <zip>6725</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Skopje, Department of Neurology</name>
      <address>
        <city>Skopje</city>
        <zip>1000</zip>
        <country>North Macedonia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jagiellonian University Medical College, Department of Neurology</name>
      <address>
        <city>Kraków</city>
        <zip>31-503</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Belgrade, Clinical Center of Serbia, Neurology Clinic, Neuropathy Center</name>
      <address>
        <city>Belgrade</city>
        <zip>11000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Hospital Center Zvezdara, Department of Neurology</name>
      <address>
        <city>Belgrad</city>
        <zip>11000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Center Niš, Department of Neurology</name>
      <address>
        <city>Niš</city>
        <zip>18000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>General Hospital &quot;Dr. Djordje Joanović&quot;</name>
      <address>
        <city>Zrenjanin</city>
        <zip>23000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Infanta Leonor</name>
      <address>
        <city>Madrid</city>
        <zip>28031</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Donostia</name>
      <address>
        <city>San Sebastián</city>
        <zip>20700</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
    <country>Hungary</country>
    <country>North Macedonia</country>
    <country>Poland</country>
    <country>Serbia</country>
    <country>Spain</country>
  </location_countries>
  <removed_countries>
    <country>Germany</country>
  </removed_countries>
  <link>
    <url>https://www.centogene.com/clinical-studies/transthyretin-related-familial-amyloidotic-small-fiber-polyneuropathy.html</url>
    <description>Related info</description>
  </link>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>October 9, 2012</study_first_submitted>
  <study_first_submitted_qc>October 11, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 12, 2012</study_first_posted>
  <last_update_submitted>June 2, 2022</last_update_submitted>
  <last_update_submitted_qc>June 2, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 6, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Transthyretin-Related (ATTR) Familial Amyloid Polyneuropathy</keyword>
  <keyword>TTR FAP</keyword>
  <keyword>Biomarker</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gastrointestinal Diseases</mesh_term>
    <mesh_term>Digestive System Diseases</mesh_term>
    <mesh_term>Neuralgia</mesh_term>
    <mesh_term>Polyneuropathies</mesh_term>
    <mesh_term>Hypotension, Orthostatic</mesh_term>
    <mesh_term>Amyloid Neuropathies</mesh_term>
    <mesh_term>Hypotension</mesh_term>
    <mesh_term>Heart Failure</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT01705626
org study id: TRAP 08-2012
nct id: NCT01705626
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
An International, multicenter, epidemiological observational study investigating the
      prevalence of Transthyretin-Related Familial Amyloidotic Polyneuropathy (TTR-FAP) in
      participants with small fiber polyneuropathy of no obvious etiology.
Transthyretin-related Familial Amyloid Polyneuropathy (TTR-FAP) is an autosomal dominant,
      progressive neurodegenerative disease, with fatal outcome occurring within ten years after
      onset. Familial amyloid polyneuropathy (FAP) associated with mutations in the transthyretin
      (TTR) gene is the most common form of genetic amyloidosis. It accounts several thousand cases
      worldwide, with Val30Met mutation identified in most patients and with endemic foci in
      Portugal, Sweden and Japan.

      TTR FAP is caused by the systemic deposition of amyloidogenic variants of the transthyretin
      protein ((Ttr) in the extra-cellular space of tissues and result in disruption of organ
      function.The typical presentation of TTR-FAP is a progressive sensory-motor polyneuropathy,
      which usually begins with loss of thermal and pain sensation in the feet, slowly ascends up
      the limbs and is associated with variable autonomic disturbances and extra-neurological
      manifestations (especially a cardiomyopathy).

      The goal of the TRAP2.1 Study is to investigate the prevalence of Transthyretin-Related
      Familial Amyloidotic Polyneuropathy (TTR-FAP) in a cohort of 500 subjects with small fiber
      polyneuropathy of no obvious etiology, based on the subject's clinical presentation.
observational model: Cohort
time perspective: Prospective
measure: Epidemiological analysis of prevalence of the TTR FAP in participants with small fiber polyneuropathy of no obvious etiology.
time frame: 3 years
description: Dry Blood Spot (DBS) samples will be genetically validated via combination of Next-Generation Sequencing (the mutation will be confirmed by Sanger sequencing) and the Multiplex ligation-dependent probe amplification (MLPA) of TTR gene
measure: Establishment of a biomarker in TTR-positive cohort
time frame: 3 years
description: Samples carrying a mutation in the TTR gene will be biochemically analyzed via liquid chromatography multiple reaction monitoring MS and compared with a merged control cohort, in order to establish TTR mutation-specific biomarker/s.
arm group label: Participants diagnosed with small fiber polyneuropathy no obvious etiology
description: Participants aged between 18 and 85 years, diagnosed with small fiber polyneuropathy of no obvious etiology, without diagnosis of alcoholism and not undergoing chemotherapy for cancer
Blood sample applied on the Dry Blood Spot (DBS) Filtercard (Centocard®)
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Peter Bauer, Prof.
role: Study Chair
affiliation: Centogene GmgH
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Austria
country: Hungary
country: North Macedonia
country: Poland
country: Serbia
country: Spain
country: Germany
url: https://www.centogene.com/clinical-studies/transthyretin-related-familial-amyloidotic-small-fiber-polyneuropathy.html
description: Related info
responsible party type: Sponsor
mesh term: Gastrointestinal Diseases
mesh term: Digestive System Diseases
mesh term: Neuralgia
mesh term: Polyneuropathies
mesh term: Hypotension, Orthostatic
mesh term: Amyloid Neuropathies
mesh term: Hypotension
mesh term: Heart Failure
sharing ipd: Undecided