<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/NCT03838991</url>
  </required_header>
  <id_info>
    <org_study_id>69HCL18_0443</org_study_id>
    <nct_id>NCT03838991</nct_id>
  </id_info>
  <brief_title>Epigenetic Regulation in Fibrous Dysplasia of Bone: mirDYS Study.</brief_title>
  <acronym>MirDYS</acronym>
  <official_title>Epigenetic Regulation of Activity and Severity of Fibrous Dysplasia in Bone: mirDYS Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospices Civils de Lyon</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospices Civils de Lyon</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>
      Fibrous dysplasia of bone is a rare congenital but non-hereditary disease caused by a&#xD;
      post-zygotic activation mutation of the GNAS gene. Patients with fibrous dysplasia may&#xD;
      present pain and bone complications (fractures, deformities..) related to their bone lesions.&#xD;
&#xD;
      For undetermined reasons, severity and disease evolution may vary considerably from patient&#xD;
      to patient.&#xD;
&#xD;
      Epigenetic regulation could then be involved, including micro Ribonucleic Acids (miRs).&#xD;
&#xD;
      These small non-coding micro Ribonucleic Acids are involved in the regulation of major steps&#xD;
      of cellular processes in different pathologies, in particular in bone diseases. However,&#xD;
      micro Ribonucleic Acids have never been studied in fibrous dysplasia.&#xD;
&#xD;
      The aim of this study is to identify micro Ribonucleic Acids significantly associated with&#xD;
      the severity of fibrous dysplasia.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 10, 2019</start_date>
  <completion_date type="Anticipated">February 10, 2025</completion_date>
  <primary_completion_date type="Anticipated">February 10, 2025</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>Evaluation of micro Ribonucleic acids expression in the serum</measure>
    <time_frame>At inclusion</time_frame>
    <description>The objective is to identify specific microRibonucleic acids expressed in serum of patients using NGS (Next Generation Sequencing).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Evaluation of micro Ribonucleic acids expression in the bone tissue</measure>
    <time_frame>At inclusion</time_frame>
    <description>The objective is to identify specific micro Ribonucleic acids expressed in bone tissue obtained from surgery (patients having a scheduled surgery for osteoarthritis or fibrous dysplasia) using NGS (Next Generation Sequencing)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Comparison of micro Ribonucleic acids expression</measure>
    <time_frame>Time of realization of the analyzes, an average of 6 months</time_frame>
    <description>The objective is to compare nature and level of expression of the micro Ribonucleic acids identify by NGS (Next Generation Sequencing) in bone tissue and serum between the 3 groups of subjects: monostotic Fibrous Dysplasia, polyostotic Fibrous Dysplasia and controls (controls are patients with osteoarthritis).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Validation of micro Ribonucleic acids identified by NGS (Next Generation Sequencing) in blood samples</measure>
    <time_frame>Time of realization of the analyzes, an average of 6 months</time_frame>
    <description>The objective is to validate expression of micro Ribonucleic acids identified by NGS (Next Generation Sequencing) in blood samples of patients from 4 pre-existing cohorts : a fibrous dysplasia cohort (PERIOSDYS) and 3 cohorts of control patients (OFELY and MODAM for women, STRAMBO for men).&#xD;
For that the expression of the significant micro Ribonucleic acids identified by NGS (Next Generation Sequencing) in sera of patients with monostotic and polyostotic fibrous dysplasia versus control patients will be measured by RT-qPCR (Reverse Transcription Quantitative Polymerase Chain Reaction) and then these results will be compared with same analysis on blood samples of patients from the 4 pre-existing cohorts.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Association between micro Ribonucleic acids and severity of fibrous dysplasia.</measure>
    <time_frame>Time of realization of the analyzes, an average of 6 months</time_frame>
    <description>Association between expression of significant micro Ribonucleic acids in patients with fibrous dysplasia with the severity of the disease will be studied by statistics analysis.&#xD;
Severity of fibrous dysplasia will be evaluated with clinical, biological and radiological data extracted from patients' medical records (Easily software) and from the CEMARA database (fibrous dysplasia database).</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">29</enrollment>
  <condition>Fibrous Dysplasia of Bone</condition>
  <arm_group>
    <arm_group_label>Monostotic fibrous dysplasia</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with monostotic Fibrous dysplasia.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Polyostotic fibrous dysplasia</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with polyostotic Fibrous dysplasia.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Controls</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Control patients having a scheduled surgery for osteoarthritis.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Blood sample</intervention_name>
    <description>A study specific blood sample will be collected.</description>
    <arm_group_label>Controls</arm_group_label>
    <arm_group_label>Monostotic fibrous dysplasia</arm_group_label>
    <arm_group_label>Polyostotic fibrous dysplasia</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Waste bone tissue</intervention_name>
    <description>For 3 patients of each group, patients having a scheduled surgery, a piece of waste bone tissue will be collected after surgery.</description>
    <arm_group_label>Controls</arm_group_label>
    <arm_group_label>Monostotic fibrous dysplasia</arm_group_label>
    <arm_group_label>Polyostotic fibrous dysplasia</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Control population :&#xD;
&#xD;
          -  men and women,&#xD;
&#xD;
          -  18 years-old and over,&#xD;
&#xD;
          -  consulting a rheumatologist or an orthopedist for arthrosis&#xD;
&#xD;
          -  have scheduled surgery for hip or knee replacement surgery or any intervention&#xD;
             involving the lower limb or upper limb.&#xD;
&#xD;
        Patients with Fibrous dysplasia:&#xD;
&#xD;
          -  men and women,&#xD;
&#xD;
          -  18 years-old and over,&#xD;
&#xD;
          -  with a diagnosis of fibrous dysplasia previously established by a rheumatologist.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Refusal to participate in the study&#xD;
&#xD;
          -  Long- term corticosteroids treatment (&gt; 3 months)&#xD;
&#xD;
          -  Treated osteoporosis&#xD;
&#xD;
          -  Chronic inflammatory rheumatism (rheumatoid arthritis, psoriasic arthritis,&#xD;
             spondyloarthropathy)&#xD;
&#xD;
          -  Collagen disease (osteogenesis imperfecta…)&#xD;
&#xD;
          -  Paget's disease, benign bone tumors&#xD;
&#xD;
          -  Uncontrolled hypo/hyper-thyroidism, hypo/hyper-parathryoidism&#xD;
&#xD;
          -  Severe renal impairment (GFR &lt; 30 ml/min/1.73m2)&#xD;
&#xD;
          -  Cancer or bone metastases (current or in the past two years)&#xD;
&#xD;
          -  Paget disease, benign bone tumor (osteoid osteoma, enchondroma …)&#xD;
&#xD;
          -  Malabsorptive disease (Celiac disease, Whipple's disease, intestinal bypass, short&#xD;
             bowel syndrome) and inflammatory bowel disease&#xD;
&#xD;
          -  Pregnant women or lactating&#xD;
&#xD;
          -  Psychiatric disorders&#xD;
&#xD;
          -  Difficulty in understanding French&#xD;
&#xD;
          -  Not a beneficiary of french social security&#xD;
&#xD;
          -  Patients protected by law&#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_contact>
    <last_name>Roland CHAPURLAT, Pr</last_name>
    <phone>04 72 11 74 81</phone>
    <phone_ext>+33</phone_ext>
    <email>roland.chapurlat@chu-lyon.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Blandine MERLE, Ph.D</last_name>
    <phone>04 72 11 74 80</phone>
    <phone_ext>+33</phone_ext>
    <email>blandine.merle@inserm.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Service de Rhumatologie &amp; INSERM U1033, Pavillon F, Hopital Edouard Herriot</name>
      <address>
        <city>Lyon</city>
        <zip>69437</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Roland CHAPURLAT, Pr</last_name>
      <phone>04 72 11 74 81</phone>
      <phone_ext>+33</phone_ext>
      <email>roland.chapurlat@chu-lyon.fr</email>
    </contact>
    <contact_backup>
      <last_name>Blandine MERLE, Ph.D</last_name>
      <phone>04 72 11 74 80</phone>
      <phone_ext>+33</phone_ext>
      <email>blandine.merle@inserm.fr</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>February 6, 2019</study_first_submitted>
  <study_first_submitted_qc>February 11, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 12, 2019</study_first_posted>
  <last_update_submitted>January 3, 2023</last_update_submitted>
  <last_update_submitted_qc>January 3, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 4, 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>Fibrous Dysplasia of Bone</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/NCT03838991
org study id: 69HCL18_0443
nct id: NCT03838991
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Fibrous dysplasia of bone is a rare congenital but non-hereditary disease caused by a
      post-zygotic activation mutation of the GNAS gene. Patients with fibrous dysplasia may
      present pain and bone complications (fractures, deformities..) related to their bone lesions.

      For undetermined reasons, severity and disease evolution may vary considerably from patient
      to patient.

      Epigenetic regulation could then be involved, including micro Ribonucleic Acids (miRs).

      These small non-coding micro Ribonucleic Acids are involved in the regulation of major steps
      of cellular processes in different pathologies, in particular in bone diseases. However,
      micro Ribonucleic Acids have never been studied in fibrous dysplasia.

      The aim of this study is to identify micro Ribonucleic Acids significantly associated with
      the severity of fibrous dysplasia.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: None (Open Label)
measure: Evaluation of micro Ribonucleic acids expression in the serum
time frame: At inclusion
description: The objective is to identify specific microRibonucleic acids expressed in serum of patients using NGS (Next Generation Sequencing).
measure: Evaluation of micro Ribonucleic acids expression in the bone tissue
time frame: At inclusion
description: The objective is to identify specific micro Ribonucleic acids expressed in bone tissue obtained from surgery (patients having a scheduled surgery for osteoarthritis or fibrous dysplasia) using NGS (Next Generation Sequencing)
measure: Comparison of micro Ribonucleic acids expression
time frame: Time of realization of the analyzes, an average of 6 months
description: The objective is to compare nature and level of expression of the micro Ribonucleic acids identify by NGS (Next Generation Sequencing) in bone tissue and serum between the 3 groups of subjects: monostotic Fibrous Dysplasia, polyostotic Fibrous Dysplasia and controls (controls are patients with osteoarthritis).
measure: Validation of micro Ribonucleic acids identified by NGS (Next Generation Sequencing) in blood samples
time frame: Time of realization of the analyzes, an average of 6 months
description: The objective is to validate expression of micro Ribonucleic acids identified by NGS (Next Generation Sequencing) in blood samples of patients from 4 pre-existing cohorts : a fibrous dysplasia cohort (PERIOSDYS) and 3 cohorts of control patients (OFELY and MODAM for women, STRAMBO for men).
For that the expression of the significant micro Ribonucleic acids identified by NGS (Next Generation Sequencing) in sera of patients with monostotic and polyostotic fibrous dysplasia versus control patients will be measured by RT-qPCR (Reverse Transcription Quantitative Polymerase Chain Reaction) and then these results will be compared with same analysis on blood samples of patients from the 4 pre-existing cohorts.
measure: Association between micro Ribonucleic acids and severity of fibrous dysplasia.
time frame: Time of realization of the analyzes, an average of 6 months
description: Association between expression of significant micro Ribonucleic acids in patients with fibrous dysplasia with the severity of the disease will be studied by statistics analysis.
Severity of fibrous dysplasia will be evaluated with clinical, biological and radiological data extracted from patients' medical records (Easily software) and from the CEMARA database (fibrous dysplasia database).
arm group label: Monostotic fibrous dysplasia
arm group type: Experimental
description: Patients with monostotic Fibrous dysplasia.
arm group label: Polyostotic fibrous dysplasia
arm group type: Experimental
description: Patients with polyostotic Fibrous dysplasia.
arm group label: Controls
arm group type: Active Comparator
description: Control patients having a scheduled surgery for osteoarthritis.
intervention type: Other
intervention name: Blood sample
description: A study specific blood sample will be collected.
arm group label: Controls
arm group label: Monostotic fibrous dysplasia
arm group label: Polyostotic fibrous dysplasia
intervention type: Other
intervention name: Waste bone tissue
description: For 3 patients of each group, patients having a scheduled surgery, a piece of waste bone tissue will be collected after surgery.
arm group label: Controls
arm group label: Monostotic fibrous dysplasia
arm group label: Polyostotic fibrous dysplasia
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Roland CHAPURLAT, Pr
phone: 04 72 11 74 81
phone ext: +33
email: roland.chapurlat@chu-lyon.fr
last name: Blandine MERLE, Ph.D
phone: 04 72 11 74 80
phone ext: +33
email: blandine.merle@inserm.fr
facility: 
status: Recruiting
contact: 
contact backup: 
country: France
responsible party type: Sponsor
mesh term: Fibrous Dysplasia of Bone
sharing ipd: No