<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/NCT03234127</url>
  </required_header>
  <id_info>
    <org_study_id>RC17_0244</org_study_id>
    <nct_id>NCT03234127</nct_id>
  </id_info>
  <brief_title>Study of cardiovAscular Contrasted Phenotypes in Patients With FamIliaI hypercholesteRolemia</brief_title>
  <acronym>SAFIR</acronym>
  <official_title>Study of cardiovAscular Contrasted Phenotypes in Patients With FamIliaI hypercholesteRolemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nantes University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Nantes University Hospital</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 main objective of SAFIR is to identify the atherosclerotic genetic factors in these&#xD;
      patients, which will identify new therapeutic targets for the treatment of CV and Familial&#xD;
      Hypercholesterolemia diseases. In addition, SAFIR will allow the identification of new CV&#xD;
      protection biomarkers, which will be useful tools for the development of a personalized&#xD;
      medicine for the management of dyslipidemias.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The objective of the SAFIR study is to perform non-invasive coronary vascular phenotyping of&#xD;
      familial hypercholesterolemia (FH) families by performing a coronary calcium score and then&#xD;
      to detect protective genetic factors in patients who do not have a significant atheroma&#xD;
      despite a perturbed biological phenotype.&#xD;
&#xD;
      The investigators will also conduct biochemical, lipidemic and metabolomic analyzes to&#xD;
      identify a signature of biomarkers protective of cardiovascular risk in FH patients.&#xD;
&#xD;
      The investigators will use the French FH register, which already includes 3889 patients, to&#xD;
      identify these &quot;protected&quot; FH families within the main reference centers for the management&#xD;
      of FH for inclusion and follow-up of patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 6, 2017</start_date>
  <completion_date type="Actual">May 6, 2021</completion_date>
  <primary_completion_date type="Actual">May 6, 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Identification of genes associated with the resistance to development of coronary atherosclerosis in subjects with heterozygous familial hypercholesterolemia</measure>
    <time_frame>3 years</time_frame>
    <description>Identification of functional genetic variants by a Whole Genome Sequencing (WGS) approach in case-control analysis (FH without and with advanced coronary atherosclerosis) and/or family analysis (protected and affected relatives)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Identification of new biochemical, lipidemic, metabolomic and metagenomic biomarkers associated with cardiovascular protection in FH patients.</measure>
    <time_frame>3 years</time_frame>
    <description>Lipidic panel, phosphocalcic panel, Ceramides, Alipoproteins, Lp(a), lipidomic, LDL size, Phospholipids, TMAO, Carnitin, Cholin, microbiota, metabolomic, LDL Ox, Sterols, Isoprostan, oxidation, inflammation, cytokins, oxidative stress.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Association of arterial stiffness (reflected by the pulse wave velocity) with the development of coronary atherosclerosis in FH patients</measure>
    <time_frame>3 years</time_frame>
    <description>Measurement of arterial stiffness measured by popmeter® (pulse wave velocity)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Association of atherosclerosis of supra-aortic trunks (AST) with the development of coronary atherosclerosis in FH patients</measure>
    <time_frame>3 years</time_frame>
    <description>Measurement of ASD through arterial Doppler ultrasonography (Intra-media thickness (IMT), degree of stenosis (ESCT), plaque)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Association of atherosclerosis of the lower limbs with the development of coronary atherosclerosis (PAD) in FH patients</measure>
    <time_frame>3 years</time_frame>
    <description>Measurement of lower extremity involvement by arterial doppler ultrasonography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Association between aortic valvular score and development of coronary atherosclerosis in FH patients</measure>
    <time_frame>3 years</time_frame>
    <description>Measurement of coronary calcium score and aortic valvular score (optional) by a thoracic CT scan</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Association between coronary calcium score and aortic valvular score in HF patients</measure>
    <time_frame>3 years</time_frame>
    <description>Measurement of coronary calcium score and aortic valvular score (optional) by a thoracic CT scan</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">562</enrollment>
  <condition>Homozygous Familial Hypercholesterolemia</condition>
  <arm_group>
    <arm_group_label>Atherosclerosis- resistance</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>FH Patient without atherosclerosis</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>FH patient with atheroclerosis</description>
  </arm_group>
  <arm_group>
    <arm_group_label>the related population without familial hypercholesterolemia</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>No FH patient</description>
  </arm_group>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>Whole Genome Sequencing</intervention_name>
    <description>Whole Genome Sequencing Biomarkers analyses</description>
    <arm_group_label>Atherosclerosis- resistance</arm_group_label>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>the related population without familial hypercholesterolemia</arm_group_label>
    <other_name>Biological analyzes</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient agreeing to sign the consent of the study and the consent of biocollection&#xD;
&#xD;
          -  Patient suffering from a familial hypercholesterolemia with a clinically-biologic&#xD;
             score DLCN (Dutch Lipid Clinic Network, Annex 2)&gt; 8 and / or a causative mutation&#xD;
             identified in the LDL receptor genes, apolipoprotein B100 or Of PCSK9.&#xD;
&#xD;
          -  Men ≥ 40 years of age; Female ≥ 50 years&#xD;
&#xD;
          -  Patient affiliated to an existing social insurance&#xD;
&#xD;
        The inclusion criteria to be met in the population with known coronary atheroma:&#xD;
&#xD;
          -  Subject in secondary prevention of an atheromatous disease: coronary event or ischemic&#xD;
             heart disease, irrespective of the result of the coronary calcium score; Ischemic&#xD;
             stroke with proven carotid atheromatosis; revascularization (angioplasty, bypass&#xD;
             surgery) or amputation in PAD&#xD;
&#xD;
          -  Primary prevention topic CV with calcium score ≥ 400 Agatston units&#xD;
&#xD;
        Inclusion criteria to be met in the population without cardiovascular risk:&#xD;
&#xD;
        - No cardiovascular event (including MI, coronary revascularization, angina, stroke &amp;,&#xD;
        Transiant ischemic attack of atheromatous origin, PAD) with: For women between 50 and 65&#xD;
        years, a nil calcium score * For women between 65 and 75 years of age, a calcium score** ≤&#xD;
        10 Agatston units For women over 75 years of age, a calcium score** ≤ 20 Agatston units For&#xD;
        men between 40 and 55 years of age, a nil calcium score* for men For men between 55 and 70&#xD;
        years of age, a calcium score** ≤ 10 Agatston units For men over 70 years of age, a calcium&#xD;
        score** ≤ 20 Agatston units&#xD;
&#xD;
          -  40 year old men and 50 year old women: less than 6 months old&#xD;
&#xD;
          -  41 year old men and 51 year old women: under 1 year old&#xD;
&#xD;
          -  42 year old men and 52 year old women: under 2 years old&#xD;
&#xD;
          -  43 year old men and 53 year old women: under 3 years old&#xD;
&#xD;
          -  44 year old men and 54 year old women: under 4 years old&#xD;
&#xD;
               -  Less than 5 years&#xD;
&#xD;
        Inclusion criteria to be met in the related population with familial hypercholesterolemia :&#xD;
&#xD;
          -  Patient agreeing to sign the consent of the study and the consent of biocollection&#xD;
&#xD;
          -  Patient suffering from a familial hypercholesterolemia with a clinically-biologic&#xD;
             score DLCN (Dutch Lipid Clinic Network, Annex 2)&gt; 8 and / or a causative mutation&#xD;
             identified in the LDL receptor genes, apolipoprotein B100 or Of PCSK9.&#xD;
&#xD;
          -  Men or Female ≥ 30 years&#xD;
&#xD;
          -  Patient affiliated to an existing social insurance&#xD;
&#xD;
        Inclusion criteria to be met in the related population without familial&#xD;
        hypercholesterolemia :&#xD;
&#xD;
          -  Patient agreeing to sign the consent of the study and the consent of biocollection&#xD;
&#xD;
          -  Patient not suffering from a familial hypercholesterolemia related to one of the&#xD;
             members of the population suffering from familial hypercholesterolemia without&#xD;
             cardiovascular risk&#xD;
&#xD;
          -  Men or Female ≥ 18 years&#xD;
&#xD;
          -  Patient affiliated to an existing social insurance&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subject suffering from active cancer or progressive neoplasia&#xD;
&#xD;
          -  Subject treated with recent corticosteroid therapy&#xD;
&#xD;
          -  Subjects with unsubstituted or poorly controlled hypothyroidism (TSH&gt; normal)&#xD;
&#xD;
          -  Subject receiving immunosuppressive or anti-cancer treatment&#xD;
&#xD;
          -  Subject refusing to participate&#xD;
&#xD;
          -  Subjects under tutelage, curatorship or a safeguard of justice or without social&#xD;
             insurance&#xD;
&#xD;
        The exclusion criterion for all populations except the related population without familial&#xD;
        hypercholesterolemia:&#xD;
&#xD;
        - Subject with no &quot;definite&quot; familial hypercholesterolemia according to the DLCN score&#xD;
        (≤8), after auction. The purpose of the auction will be to rule on the causal nature of an&#xD;
        identified mutation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Le Bocage Hospital</name>
      <address>
        <city>Dijon</city>
        <zip>29079</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHRU de Lille</name>
      <address>
        <city>Lille</city>
        <zip>59037</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Louis Pradel Cardiovascular Hospital</name>
      <address>
        <city>Lyon</city>
        <zip>69677</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>La Conception Hospital</name>
      <address>
        <city>Marseille</city>
        <zip>13285</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nantes University Hospital</name>
      <address>
        <city>Nantes</city>
        <zip>44093</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint-Antoine Hospital</name>
      <address>
        <city>Paris</city>
        <zip>75012</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pitié-Salpêtrière Hospital</name>
      <address>
        <city>Paris</city>
        <zip>75013</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rennes University Hospital</name>
      <address>
        <city>Rennes</city>
        <zip>35033</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Toulouse Hospital</name>
      <address>
        <city>Toulouse</city>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>July 26, 2017</study_first_submitted>
  <study_first_submitted_qc>July 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 31, 2017</study_first_posted>
  <last_update_submitted>May 21, 2021</last_update_submitted>
  <last_update_submitted_qc>May 21, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 24, 2021</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>Hyperlipoproteinemia Type II</mesh_term>
    <mesh_term>Homozygous Familial Hypercholesterolemia</mesh_term>
    <mesh_term>Hypercholesterolemia</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/NCT03234127
org study id: RC17_0244
nct id: NCT03234127
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The main objective of SAFIR is to identify the atherosclerotic genetic factors in these
      patients, which will identify new therapeutic targets for the treatment of CV and Familial
      Hypercholesterolemia diseases. In addition, SAFIR will allow the identification of new CV
      protection biomarkers, which will be useful tools for the development of a personalized
      medicine for the management of dyslipidemias.
The objective of the SAFIR study is to perform non-invasive coronary vascular phenotyping of
      familial hypercholesterolemia (FH) families by performing a coronary calcium score and then
      to detect protective genetic factors in patients who do not have a significant atheroma
      despite a perturbed biological phenotype.

      The investigators will also conduct biochemical, lipidemic and metabolomic analyzes to
      identify a signature of biomarkers protective of cardiovascular risk in FH patients.

      The investigators will use the French FH register, which already includes 3889 patients, to
      identify these "protected" FH families within the main reference centers for the management
      of FH for inclusion and follow-up of patients.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: None (Open Label)
measure: Identification of genes associated with the resistance to development of coronary atherosclerosis in subjects with heterozygous familial hypercholesterolemia
time frame: 3 years
description: Identification of functional genetic variants by a Whole Genome Sequencing (WGS) approach in case-control analysis (FH without and with advanced coronary atherosclerosis) and/or family analysis (protected and affected relatives)
measure: Identification of new biochemical, lipidemic, metabolomic and metagenomic biomarkers associated with cardiovascular protection in FH patients.
time frame: 3 years
description: Lipidic panel, phosphocalcic panel, Ceramides, Alipoproteins, Lp(a), lipidomic, LDL size, Phospholipids, TMAO, Carnitin, Cholin, microbiota, metabolomic, LDL Ox, Sterols, Isoprostan, oxidation, inflammation, cytokins, oxidative stress.
measure: Association of arterial stiffness (reflected by the pulse wave velocity) with the development of coronary atherosclerosis in FH patients
time frame: 3 years
description: Measurement of arterial stiffness measured by popmeter® (pulse wave velocity)
measure: Association of atherosclerosis of supra-aortic trunks (AST) with the development of coronary atherosclerosis in FH patients
time frame: 3 years
description: Measurement of ASD through arterial Doppler ultrasonography (Intra-media thickness (IMT), degree of stenosis (ESCT), plaque)
measure: Association of atherosclerosis of the lower limbs with the development of coronary atherosclerosis (PAD) in FH patients
time frame: 3 years
description: Measurement of lower extremity involvement by arterial doppler ultrasonography
measure: Association between aortic valvular score and development of coronary atherosclerosis in FH patients
time frame: 3 years
description: Measurement of coronary calcium score and aortic valvular score (optional) by a thoracic CT scan
measure: Association between coronary calcium score and aortic valvular score in HF patients
time frame: 3 years
description: Measurement of coronary calcium score and aortic valvular score (optional) by a thoracic CT scan
arm group label: Atherosclerosis- resistance
arm group type: Other
description: FH Patient without atherosclerosis
arm group label: Control
arm group type: Other
description: FH patient with atheroclerosis
arm group label: the related population without familial hypercholesterolemia
arm group type: Other
description: No FH patient
intervention type: Genetic
intervention name: Whole Genome Sequencing
description: Whole Genome Sequencing Biomarkers analyses
arm group label: Atherosclerosis- resistance
arm group label: Control
arm group label: the related population without familial hypercholesterolemia
other name: Biological analyzes
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: France
responsible party type: Sponsor
mesh term: Hyperlipoproteinemia Type II
mesh term: Homozygous Familial Hypercholesterolemia
mesh term: Hypercholesterolemia
sharing ipd: Undecided