xml: <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/NCT05974644</url>
    </required_header>
    <id_info>
      <org_study_id>HM20027103</org_study_id>
      <nct_id>NCT05974644</nct_id>
    </id_info>
    <brief_title>Southeastern ATTR Amyloidosis Consortium: SEATTRAC Family Registry</brief_title>
    <official_title>Southeastern ATTR Amyloidosis Consortium: SEATTRAC Family Registry</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Virginia Commonwealth University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Virginia Commonwealth University</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>
        The study design is a prospective registry including asymptomatic and symptomatic patients&#xD;
        who carry a pathogenic TTR mutation. The study will enroll patients who meet the inclusion&#xD;
        criteria and none of the exclusion criteria until 1000 patients are enrolled, at which point&#xD;
        in time the study investigators will evaluate whether further patient accrual is meaningful.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Hereditary transthyretin amyloidosis (hATTR) is an autosomal dominant disorder caused by a&#xD;
        pathogenic mutation of the transthyretin (TTR) gene. The mutated gene destabilizes the TTR&#xD;
        tetramer causing it to dissociate, misfold and accumulate as insoluble extracellular amyloid&#xD;
        fibrils. These fibrils then deposit in various organs and tissues leading to organ&#xD;
        dysfunction and destruction. There are more than 130 known pathogenic mutations of the TTR&#xD;
        gene leading to hATTR with predominantly neurologic or cardiac clinical manifestations.&#xD;
  &#xD;
        The V142I mutation (historically reported as V122I prior to the opening 20-amino acid&#xD;
        sequence being included to the position count) is the most prevalent mutation in the United&#xD;
        States. This mutation is carried by 3-4% of the Black population with a founder variant&#xD;
        originating in West Africa. It was brought to the Western Hemisphere during the Atlantic&#xD;
        slave trade. The presence of the mutation has been associated with increased risk of heart&#xD;
        failure, however with incomplete penetrance of an amyloid cardiomyopathy phenotype. With&#xD;
        improved accessibility to genetic testing and noninvasive techniques with bone scintigraphy&#xD;
        to diagnose TTR deposition in the heart, the identification of disease has dramatically&#xD;
        increased. As a result, genetic counseling and cascade testing has identified a growing pool&#xD;
        of asymptomatic, at-risk family members for whom counseling and surveillance is undefined.&#xD;
  &#xD;
        There is a paucity of data for V142I carriers including poor understanding of disease&#xD;
        penetrance, timing of disease onset as well as onset of extracardiac manifestations. Prior&#xD;
        studies that sought to understand disease penetrance and early clinical predictors of&#xD;
        phenotype presentation were limited due to geographic variation, historical under-recognition&#xD;
        of the disease, poor enrollment of Black V142I patients into clinical studies and missing&#xD;
        data due to retrospective study designs. For example, the often-cited THAOS (Transthyretin&#xD;
        Amyloidosis Outcomes Survey) registry demonstrated enrollment limitations. Of the 740 total&#xD;
        asymptomatic hATTR mutation carriers studied, only 10 asymptomatic subjects had the V142&#xD;
        mutation.&#xD;
  &#xD;
        Better described neuropathic or mixed variants (i.e. T80A [formerly T60A] and V50M [formerly&#xD;
        V30M] are often associated with easily detectable, clinically debilitating and rapidly&#xD;
        progressing disease earlier in life. Conversely the V142I phenotype presents later in life&#xD;
        primarily with a cardiomyopathy that may mimic hypertensive heart disease or heart failure&#xD;
        with preserved ejection fraction. Oftentimes symptoms in the older V142I patient population&#xD;
        are attributed to other comorbidities such as diabetes, hypertension or valve disease. This&#xD;
        contributes to a delay in the diagnosis of hATTR diagnosis or a miss altogether. Identifying&#xD;
        early clinical predictors of disease presentation may offer an opportunity for meaningful&#xD;
        interruption of disease progression with newly available disease modifying therapies.&#xD;
  &#xD;
        In this study, members of the Southeastern ATTR Amyloidosis Consortium (SEATTRAC) will enroll&#xD;
        asymptomatic carriers of pathogenic TTR mutations and hATTR cardiac amyloidosis patients in a&#xD;
        prospective registry. SEATTRAC members include high volume amyloidosis centers that are not&#xD;
        only destination centers for amyloidosis care, but comprehensively serve their local and&#xD;
        regional communities. We anticipate that such a registry will be the first to describe the&#xD;
        clinical course of disease and outcomes for asymptomatic carriers of the V142I mutation, the&#xD;
        hATTR variant that predominantly afflicts Black Americans.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2024</start_date>
    <completion_date type="Anticipated">December 1, 2030</completion_date>
    <primary_completion_date type="Anticipated">December 1, 2030</primary_completion_date>
    <study_type>Observational [Patient Registry]</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>
    <target_duration>3 Years</target_duration>
    <primary_outcome>
      <measure>The predictors and incidence of amyloidosis</measure>
      <time_frame>15 years</time_frame>
      <description>For those enrolled as asymptomatic carriers, it will be assessed if they develop cardiac or extra cardiac amyloidosis</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Mortality and/or need for heart transplant</measure>
      <time_frame>10 years</time_frame>
      <description>For those with cardiac hereditary transthyretin amyloidosis (hATTR), it will be assessed how many participants die due to disease or require a heart transplant</description>
    </primary_outcome>
    <number_of_groups>2</number_of_groups>
    <enrollment type="Anticipated">1000</enrollment>
    <condition>Amyloidosis, Hereditary</condition>
    <arm_group>
      <arm_group_label>Asymptomatic carriers</arm_group_label>
    </arm_group>
    <arm_group>
      <arm_group_label>Patients with cardiac hereditary transthyretin amyloidosis (hATTR)</arm_group_label>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Registry</intervention_name>
      <description>The purpose of this registry is to collect and store health information from people who are carriers of the gene known to cause hereditary amyloidosis and those with a confirmed diagnosis of the disease.</description>
      <arm_group_label>Asymptomatic carriers</arm_group_label>
      <arm_group_label>Patients with cardiac hereditary transthyretin amyloidosis (hATTR)</arm_group_label>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          Any carriers of a pathogenic TTR mutation known to cause hATTR amyloidosis will be&#xD;
          recruited to the registry.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Over the age of 18 years&#xD;
  &#xD;
            -  Carrier of a pathogenic hATTR mutation confirmed on whole blood gene testing or mass&#xD;
               spectrometry&#xD;
  &#xD;
            -  Willing to return for required follow-up visits&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Patient having undergone heart transplantation or implantation of mechanical&#xD;
               circulatory support&#xD;
  &#xD;
            -  Patients unable to provide informed consent&#xD;
  &#xD;
            -  Patients having undergone liver transplantation&#xD;
  &#xD;
            -  Patients have evidence of light chain amyloidosis&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Keyur Shah, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Virginia Commonwealth University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Keyur Shah, MD</last_name>
      <phone>804-828-4571</phone>
      <email>keyur.shah@vcuhealth.org</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Sarah Paciulli, NP</last_name>
      <phone>804-828-4571</phone>
      <email>sarah.paciulli@vcuhealth.org</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Virginia Commonwealth University</name>
        <address>
          <city>Richmond</city>
          <state>Virginia</state>
          <zip>23298</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Keyur Shah, MD</last_name>
        <phone>804-828-4571</phone>
        <email>keyur.shah@vcuhealth.org</email>
      </contact>
      <investigator>
        <last_name>Keyur Shah, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 14, 2023</study_first_submitted>
    <study_first_submitted_qc>July 25, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 3, 2023</study_first_posted>
    <last_update_submitted>July 25, 2023</last_update_submitted>
    <last_update_submitted_qc>July 25, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 3, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Amyloidosis, Familial</mesh_term>
      <mesh_term>Amyloidosis</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>Deidentified data will be provided to the other investigators as a limited data set if requested.</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_time_frame>Duration of the registry</ipd_time_frame>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05974644
  org study id: HM20027103
  nct id: NCT05974644
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The study design is a prospective registry including asymptomatic and symptomatic patients
        who carry a pathogenic TTR mutation. The study will enroll patients who meet the inclusion
        criteria and none of the exclusion criteria until 1000 patients are enrolled, at which point
        in time the study investigators will evaluate whether further patient accrual is meaningful.
  Hereditary transthyretin amyloidosis (hATTR) is an autosomal dominant disorder caused by a
        pathogenic mutation of the transthyretin (TTR) gene. The mutated gene destabilizes the TTR
        tetramer causing it to dissociate, misfold and accumulate as insoluble extracellular amyloid
        fibrils. These fibrils then deposit in various organs and tissues leading to organ
        dysfunction and destruction. There are more than 130 known pathogenic mutations of the TTR
        gene leading to hATTR with predominantly neurologic or cardiac clinical manifestations.
  
        The V142I mutation (historically reported as V122I prior to the opening 20-amino acid
        sequence being included to the position count) is the most prevalent mutation in the United
        States. This mutation is carried by 3-4% of the Black population with a founder variant
        originating in West Africa. It was brought to the Western Hemisphere during the Atlantic
        slave trade. The presence of the mutation has been associated with increased risk of heart
        failure, however with incomplete penetrance of an amyloid cardiomyopathy phenotype. With
        improved accessibility to genetic testing and noninvasive techniques with bone scintigraphy
        to diagnose TTR deposition in the heart, the identification of disease has dramatically
        increased. As a result, genetic counseling and cascade testing has identified a growing pool
        of asymptomatic, at-risk family members for whom counseling and surveillance is undefined.
  
        There is a paucity of data for V142I carriers including poor understanding of disease
        penetrance, timing of disease onset as well as onset of extracardiac manifestations. Prior
        studies that sought to understand disease penetrance and early clinical predictors of
        phenotype presentation were limited due to geographic variation, historical under-recognition
        of the disease, poor enrollment of Black V142I patients into clinical studies and missing
        data due to retrospective study designs. For example, the often-cited THAOS (Transthyretin
        Amyloidosis Outcomes Survey) registry demonstrated enrollment limitations. Of the 740 total
        asymptomatic hATTR mutation carriers studied, only 10 asymptomatic subjects had the V142
        mutation.
  
        Better described neuropathic or mixed variants (i.e. T80A [formerly T60A] and V50M [formerly
        V30M] are often associated with easily detectable, clinically debilitating and rapidly
        progressing disease earlier in life. Conversely the V142I phenotype presents later in life
        primarily with a cardiomyopathy that may mimic hypertensive heart disease or heart failure
        with preserved ejection fraction. Oftentimes symptoms in the older V142I patient population
        are attributed to other comorbidities such as diabetes, hypertension or valve disease. This
        contributes to a delay in the diagnosis of hATTR diagnosis or a miss altogether. Identifying
        early clinical predictors of disease presentation may offer an opportunity for meaningful
        interruption of disease progression with newly available disease modifying therapies.
  
        In this study, members of the Southeastern ATTR Amyloidosis Consortium (SEATTRAC) will enroll
        asymptomatic carriers of pathogenic TTR mutations and hATTR cardiac amyloidosis patients in a
        prospective registry. SEATTRAC members include high volume amyloidosis centers that are not
        only destination centers for amyloidosis care, but comprehensively serve their local and
        regional communities. We anticipate that such a registry will be the first to describe the
        clinical course of disease and outcomes for asymptomatic carriers of the V142I mutation, the
        hATTR variant that predominantly afflicts Black Americans.
  observational model: Cohort
  time perspective: Prospective
  measure: The predictors and incidence of amyloidosis
  time frame: 15 years
  description: For those enrolled as asymptomatic carriers, it will be assessed if they develop cardiac or extra cardiac amyloidosis
  measure: Mortality and/or need for heart transplant
  time frame: 10 years
  description: For those with cardiac hereditary transthyretin amyloidosis (hATTR), it will be assessed how many participants die due to disease or require a heart transplant
  arm group label: Asymptomatic carriers
  arm group label: Patients with cardiac hereditary transthyretin amyloidosis (hATTR)
  intervention type: Other
  intervention name: Registry
  description: The purpose of this registry is to collect and store health information from people who are carriers of the gene known to cause hereditary amyloidosis and those with a confirmed diagnosis of the disease.
  arm group label: Asymptomatic carriers
  arm group label: Patients with cardiac hereditary transthyretin amyloidosis (hATTR)
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Keyur Shah, MD
  role: Principal Investigator
  affiliation: Virginia Commonwealth University
  last name: Keyur Shah, MD
  phone: 804-828-4571
  email: keyur.shah@vcuhealth.org
  last name: Sarah Paciulli, NP
  phone: 804-828-4571
  email: sarah.paciulli@vcuhealth.org
  facility: 
  contact: 
  investigator: 
  country: United States
  responsible party type: Sponsor
  mesh term: Amyloidosis, Familial
  mesh term: Amyloidosis
  sharing ipd: Yes
  ipd description: Deidentified data will be provided to the other investigators as a limited data set if requested.
  ipd info type: Study Protocol
  ipd time frame: Duration of the registry