<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/NCT04419987</url>
  </required_header>
  <id_info>
    <org_study_id>2019-30</org_study_id>
    <nct_id>NCT04419987</nct_id>
  </id_info>
  <brief_title>Study of Constitutional Platelet Disease</brief_title>
  <acronym>EVGPP</acronym>
  <official_title>Study of the Functionality of New Genetic Variants at the Origin of Constitutional Platelet Disease.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique Hopitaux De Marseille</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique Hopitaux De Marseille</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>
      Platelets are circulating blood cells. They bind to each other and to the wall of the damaged&#xD;
      vessel to prevent excessive blood loss.&#xD;
&#xD;
      Platelets can be :&#xD;
&#xD;
        -  insufficient in number in the case of thrombocytopenia;&#xD;
&#xD;
        -  or non-functional in the case of thrombopathy. Constitutional thrombopathies and&#xD;
           thrombopenias are rare diseases. Constitutional thrombopenias cause haemorrhage of&#xD;
           variable intensity and are sometimes a sign of more serious haematological pathologies.&#xD;
           The evolutionary risk of some constitutional thrombopenias is the appearance of&#xD;
           myelofibrosis, dysmyelopoiesis or malignant proliferation. While the evolutionary stakes&#xD;
           of some thrombopenias and especially syndromic thrombopenias will be more likely to&#xD;
           affect other organs (kidney, heart, bones, brain, ...), other constitutional&#xD;
           thrombopenias will have few consequences. Their diagnosis will then have the major&#xD;
           challenge of distinguishing them from immunological thrombopenias and avoiding the use&#xD;
           of inappropriate and sometimes severe treatments (corticosteroids, IV immunoglobulins,&#xD;
           immunosuppressants, splenectomy). Mutations in more than forty genes have been&#xD;
           identified to date and are responsible for thrombocytopenia.&#xD;
&#xD;
      Constitutional thrombopathies are heterogeneous and may involve different platelet&#xD;
      constituents. In short, when platelets are stimulated at a lesion site, various soluble or&#xD;
      matrix agonists bind to platelet receptors to induce calcium flow, secretion and platelet&#xD;
      aggregation at a vascular gap to prevent blood loss. Constitutional thrombopathies are&#xD;
      primarily at risk of spontaneous or induced mucocutaneous bleeding. Some thrombopathies are&#xD;
      also part of more complex syndromic patterns. In recent decades, considerable progress has&#xD;
      been made in the understanding of thrombopathies, enabling them to be better identified.&#xD;
      Details have been provided on platelet dysfunctions linked to abnormalities in the processes&#xD;
      of granule biogenesis and secretion, and to signalling defects (in particular surface&#xD;
      receptor deficiency). Currently, more than thirty genes are the site of autosomal dominant,&#xD;
      recessive or X-linked mutations and can be sequenced.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Platelets are circulating blood cells. They bind to each other and to the wall of the damaged&#xD;
      vessel to prevent excessive blood loss.&#xD;
&#xD;
      Platelets can be :&#xD;
&#xD;
        -  insufficient in number in the case of thrombocytopenia;&#xD;
&#xD;
        -  or non-functional in the case of thrombopathy. Constitutional thrombopathies and&#xD;
           thrombopenias are rare diseases. Constitutional thrombopenias cause haemorrhage of&#xD;
           variable intensity and are sometimes a sign of more serious haematological pathologies.&#xD;
           The evolutionary risk of some constitutional thrombopenias is the appearance of&#xD;
           myelofibrosis, dysmyelopoiesis or malignant proliferation. While the evolutionary stakes&#xD;
           of some thrombopenias and especially syndromic thrombopenias will be more likely to&#xD;
           affect other organs (kidney, heart, bones, brain, ...), other constitutional&#xD;
           thrombopenias will have few consequences. Their diagnosis will then have the major&#xD;
           challenge of distinguishing them from immunological thrombopenias and avoiding the use&#xD;
           of inappropriate and sometimes severe treatments (corticosteroids, IV immunoglobulins,&#xD;
           immunosuppressants, splenectomy). Mutations in more than forty genes have been&#xD;
           identified to date and are responsible for thrombocytopenia.&#xD;
&#xD;
      Constitutional thrombopathies are heterogeneous and may involve different platelet&#xD;
      constituents. In short, when platelets are stimulated at a lesion site, various soluble or&#xD;
      matrix agonists bind to platelet receptors to induce calcium flow, secretion and platelet&#xD;
      aggregation at a vascular gap to prevent blood loss. Constitutional thrombopathies are&#xD;
      primarily at risk of spontaneous or induced mucocutaneous bleeding. Some thrombopathies are&#xD;
      also part of more complex syndromic patterns. In recent decades, considerable progress has&#xD;
      been made in the understanding of thrombopathies, enabling them to be better identified.&#xD;
      Details have been provided on platelet dysfunctions linked to abnormalities in the processes&#xD;
      of granule biogenesis and secretion, and to signalling defects (in particular surface&#xD;
      receptor deficiency). Currently, more than thirty genes are the site of autosomal dominant,&#xD;
      recessive or X-linked mutations and can be sequenced.&#xD;
&#xD;
      A national organisation has been set up for the molecular diagnosis of these pathologies. DNA&#xD;
      samples from patients meeting strict criteria (familial nature, chronic pathology, associated&#xD;
      signs) are sent to the molecular biology departments. A panel of 80 genes is then sequenced&#xD;
      in order to identify genetic variations potentially responsible for the pathology. In 40% of&#xD;
      cases, a diagnosis of certainty will be made. For the remaining 60%, the analysis will remain&#xD;
      non-informative for several reasons:&#xD;
&#xD;
        -  Either it is a question of revealing a variation in a known gene but not yet described&#xD;
           in the literature, the deleterious nature of which must be confirmed;&#xD;
&#xD;
        -  or no gene has been identified and there will be an indication of a broader sequencing&#xD;
           involving all exons in the genome. This strategy has already enabled the coordinating&#xD;
           site to identify several new genes of particular importance;&#xD;
&#xD;
        -  either they are individuals for which the constitutional character was not sufficiently&#xD;
           documented, a diagnostic reorientation will then be necessary.&#xD;
&#xD;
      This project will consist of proving the deleterious nature of new genetic variations using&#xD;
      cellular and molecular biology methods. These variations will be either those identified on a&#xD;
      known gene in the context of diagnosis (sequencing of a panel of genes) or those identified&#xD;
      by sequencing exons on a gene not yet known to be involved in constitutional platelet&#xD;
      pathologies. The sequencing of exons is an integral part of the project.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">July 20, 2020</start_date>
  <completion_date type="Anticipated">June 1, 2025</completion_date>
  <primary_completion_date type="Anticipated">December 20, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Adhesion</measure>
    <time_frame>5 years</time_frame>
    <description>Isolated wafers are deposited on substrate coated plates, the wafers adhere to the substrate. Then the number of adherent wafers will be counted by cell imaging. Several substrates will be tested.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Study of platelet protein expression</measure>
    <time_frame>5 years</time_frame>
    <description>A western blot will be made from the platelet lysate, allowing the detection of specific proteins with the help of antibodies directed against the proteins of interest.&#xD;
A semi-quantitative analysis of these proteins will be performed by chemiluminescence.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">600</enrollment>
  <condition>Blood Platelet Disease</condition>
  <arm_group>
    <arm_group_label>constitutional platelet patholog</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patient and relatives having a constitutional platelet pathology</description>
  </arm_group>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>draw blood</intervention_name>
    <description>search for new genetic variations (when the diagnostic exploration will have been non informative) by sequencing exons.</description>
    <arm_group_label>constitutional platelet patholog</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult or minor over 7 years old.&#xD;
&#xD;
          -  Patient and relatives with a constitutional platelet pathology (familial&#xD;
             thrombocytopenia resulting in a platelet count &lt; 150 G.L-1 in several family members&#xD;
             and/or familial thrombopathy resulting in platelet dysfunction in several members of a&#xD;
             family) for which a genetic variation has been demonstrated but whose deleterious&#xD;
             nature remains to be confirmed.&#xD;
&#xD;
          -  Patient and relatives having a constitutional platelet pathology (familial&#xD;
             thrombocytopenia resulting in a platelet count &lt; 150 G.L-1 in several members of the&#xD;
             family and/or familial thrombopathy resulting in platelet dysfunction in several&#xD;
             members of a family) for which the genetic diagnosis has not revealed any variation&#xD;
             potentially implicated in the pathology.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Minor under 7 years of age.&#xD;
&#xD;
          -  Patient with no platelet pathology.&#xD;
&#xD;
          -  Patient with platelet disease: non-chronic, non-familial.&#xD;
&#xD;
          -  Patient with a familial platelet disease with a known deleterious mutation.obviously&#xD;
             acquired.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>7 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Marie-Christine ALESSI</last_name>
    <phone>4 91 32 45 06</phone>
    <phone_ext>+33</phone_ext>
    <email>marie-christine.alessi@univ-amu.fr</email>
  </overall_contact>
  <verification_date>April 2020</verification_date>
  <study_first_submitted>May 3, 2020</study_first_submitted>
  <study_first_submitted_qc>June 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>July 7, 2020</last_update_submitted>
  <last_update_submitted_qc>July 7, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 9, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <!-- 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/NCT04419987
org study id: 2019-30
nct id: NCT04419987
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Platelets are circulating blood cells. They bind to each other and to the wall of the damaged
      vessel to prevent excessive blood loss.

      Platelets can be :

        -  insufficient in number in the case of thrombocytopenia;

        -  or non-functional in the case of thrombopathy. Constitutional thrombopathies and
           thrombopenias are rare diseases. Constitutional thrombopenias cause haemorrhage of
           variable intensity and are sometimes a sign of more serious haematological pathologies.
           The evolutionary risk of some constitutional thrombopenias is the appearance of
           myelofibrosis, dysmyelopoiesis or malignant proliferation. While the evolutionary stakes
           of some thrombopenias and especially syndromic thrombopenias will be more likely to
           affect other organs (kidney, heart, bones, brain, ...), other constitutional
           thrombopenias will have few consequences. Their diagnosis will then have the major
           challenge of distinguishing them from immunological thrombopenias and avoiding the use
           of inappropriate and sometimes severe treatments (corticosteroids, IV immunoglobulins,
           immunosuppressants, splenectomy). Mutations in more than forty genes have been
           identified to date and are responsible for thrombocytopenia.

      Constitutional thrombopathies are heterogeneous and may involve different platelet
      constituents. In short, when platelets are stimulated at a lesion site, various soluble or
      matrix agonists bind to platelet receptors to induce calcium flow, secretion and platelet
      aggregation at a vascular gap to prevent blood loss. Constitutional thrombopathies are
      primarily at risk of spontaneous or induced mucocutaneous bleeding. Some thrombopathies are
      also part of more complex syndromic patterns. In recent decades, considerable progress has
      been made in the understanding of thrombopathies, enabling them to be better identified.
      Details have been provided on platelet dysfunctions linked to abnormalities in the processes
      of granule biogenesis and secretion, and to signalling defects (in particular surface
      receptor deficiency). Currently, more than thirty genes are the site of autosomal dominant,
      recessive or X-linked mutations and can be sequenced.
Platelets are circulating blood cells. They bind to each other and to the wall of the damaged
      vessel to prevent excessive blood loss.

      Platelets can be :

        -  insufficient in number in the case of thrombocytopenia;

        -  or non-functional in the case of thrombopathy. Constitutional thrombopathies and
           thrombopenias are rare diseases. Constitutional thrombopenias cause haemorrhage of
           variable intensity and are sometimes a sign of more serious haematological pathologies.
           The evolutionary risk of some constitutional thrombopenias is the appearance of
           myelofibrosis, dysmyelopoiesis or malignant proliferation. While the evolutionary stakes
           of some thrombopenias and especially syndromic thrombopenias will be more likely to
           affect other organs (kidney, heart, bones, brain, ...), other constitutional
           thrombopenias will have few consequences. Their diagnosis will then have the major
           challenge of distinguishing them from immunological thrombopenias and avoiding the use
           of inappropriate and sometimes severe treatments (corticosteroids, IV immunoglobulins,
           immunosuppressants, splenectomy). Mutations in more than forty genes have been
           identified to date and are responsible for thrombocytopenia.

      Constitutional thrombopathies are heterogeneous and may involve different platelet
      constituents. In short, when platelets are stimulated at a lesion site, various soluble or
      matrix agonists bind to platelet receptors to induce calcium flow, secretion and platelet
      aggregation at a vascular gap to prevent blood loss. Constitutional thrombopathies are
      primarily at risk of spontaneous or induced mucocutaneous bleeding. Some thrombopathies are
      also part of more complex syndromic patterns. In recent decades, considerable progress has
      been made in the understanding of thrombopathies, enabling them to be better identified.
      Details have been provided on platelet dysfunctions linked to abnormalities in the processes
      of granule biogenesis and secretion, and to signalling defects (in particular surface
      receptor deficiency). Currently, more than thirty genes are the site of autosomal dominant,
      recessive or X-linked mutations and can be sequenced.

      A national organisation has been set up for the molecular diagnosis of these pathologies. DNA
      samples from patients meeting strict criteria (familial nature, chronic pathology, associated
      signs) are sent to the molecular biology departments. A panel of 80 genes is then sequenced
      in order to identify genetic variations potentially responsible for the pathology. In 40% of
      cases, a diagnosis of certainty will be made. For the remaining 60%, the analysis will remain
      non-informative for several reasons:

        -  Either it is a question of revealing a variation in a known gene but not yet described
           in the literature, the deleterious nature of which must be confirmed;

        -  or no gene has been identified and there will be an indication of a broader sequencing
           involving all exons in the genome. This strategy has already enabled the coordinating
           site to identify several new genes of particular importance;

        -  either they are individuals for which the constitutional character was not sufficiently
           documented, a diagnostic reorientation will then be necessary.

      This project will consist of proving the deleterious nature of new genetic variations using
      cellular and molecular biology methods. These variations will be either those identified on a
      known gene in the context of diagnosis (sequencing of a panel of genes) or those identified
      by sequencing exons on a gene not yet known to be involved in constitutional platelet
      pathologies. The sequencing of exons is an integral part of the project.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Adhesion
time frame: 5 years
description: Isolated wafers are deposited on substrate coated plates, the wafers adhere to the substrate. Then the number of adherent wafers will be counted by cell imaging. Several substrates will be tested.
measure: Study of platelet protein expression
time frame: 5 years
description: A western blot will be made from the platelet lysate, allowing the detection of specific proteins with the help of antibodies directed against the proteins of interest.
A semi-quantitative analysis of these proteins will be performed by chemiluminescence.
arm group label: constitutional platelet patholog
arm group type: Experimental
description: Patient and relatives having a constitutional platelet pathology
intervention type: Genetic
intervention name: draw blood
description: search for new genetic variations (when the diagnostic exploration will have been non informative) by sequencing exons.
arm group label: constitutional platelet patholog
criteria: 
gender: All
minimum age: 7 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Marie-Christine ALESSI
phone: 4 91 32 45 06
phone ext: +33
email: marie-christine.alessi@univ-amu.fr
responsible party type: Sponsor