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/NCT06034795</url>
    </required_header>
    <id_info>
      <org_study_id>q3e689cu</org_study_id>
      <nct_id>NCT06034795</nct_id>
    </id_info>
    <brief_title>Evaluation of Bone Metabolism in Children and Adolescents With Familial Mediterranean Fever</brief_title>
    <acronym>FMF</acronym>
    <official_title>Evaluation of Bone Metabolism in Children and Adolescents With Familial Mediterranean Fever and Correlation With Genotype</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Aristotle University Of Thessaloniki</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Papageorgiou General Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Aristotle University Of Thessaloniki</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>
        Familial Mediterranean Fever is a chronic auto-inflammatory disease. In the context of&#xD;
        chronic inflammation, it seems that, among others, it also affects bone density in children.&#xD;
        Bone loss may be due to subclinical inflammation that persists even during periods of&#xD;
        remission. In addition, inflammatory cytokines also play an important role (mainly during&#xD;
        episodes) resulting in an increase in bone degradation and ultimately a reduction in bone&#xD;
        mass. Cytokines mainly associated with bone degradation and osteoclast activity are: IL-1R,&#xD;
        IL-2, IL-6, IL-8, TNFa.&#xD;
  &#xD;
        The purpose of this study is to determine the effect of FMF on bone density and to compare&#xD;
        the results with a healthy population. In addition, the difference between the children with&#xD;
        FMF will be studied according to the mutation they carry.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        For the above purpose, 62 children will participate, 31 healthy and 31 with FMF(confirmed&#xD;
        mutation/s in the MEFV (Marenostrin Encoding Fever Gene) ).&#xD;
  &#xD;
        They will be separated based on gender (boys, girls) and age: 2 age groups: a) 6-12 years, b)&#xD;
        12 - 20 years, separation into pre-adolescent children and adolescents (according to Tanner)&#xD;
        and Body Mass Index ( BMI) (3rd-90th ED). Of the 31 children with FMF, all will be treated&#xD;
        with colchicine and the study will not take place during periods of disease attack.&#xD;
  &#xD;
        An attack free period is defined as a period of at least 3 weeks without clinical symptoms&#xD;
        (fever, abdominal pain, arthritis) and without acute phase indicators (increased CRP, TKE,&#xD;
        WBC).&#xD;
  &#xD;
        The healthy population will exclude children with a history of disease related to a bone&#xD;
        disorder. In addition, the existence of other factors that could affect bone density will be&#xD;
        investigated in all 62 children. For this reason, there will be a check of calcium&#xD;
        metabolism, vitamin D, kidney function, hormonal check, thyroid function check. Biomarkers of&#xD;
        the RANK/RANKL/OPG axis that have a major role in osteoblast/osteoclast activity will be&#xD;
        tested. Children's physical activity will be also assessed.&#xD;
  &#xD;
        Bone density measurement will be done with a Hologic DISCOVERY QDR DXA (Dual Energy X-ray&#xD;
        Absorptiometry) machine, the &quot;gold standard&quot; for spine and hip bone disorder screening&#xD;
        worldwide. The program to be implemented will be adapted to childhood.&#xD;
  &#xD;
        Then the following will be assessed: Body Mineral Density (BMD), Body Mineral Content (BMC)&#xD;
        and z-score for the vertebrae of the OMSS (O1-O4) and Total Body less Head (TBLH).&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">January 8, 2022</start_date>
    <completion_date type="Anticipated">January 2025</completion_date>
    <primary_completion_date type="Anticipated">January 2024</primary_completion_date>
    <study_type>Observational [Patient Registry]</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Case-Control</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <target_duration>3 Years</target_duration>
    <primary_outcome>
      <measure>Effect of chronic inflammation of FMF on bone metabolism</measure>
      <time_frame>The evaluation of bone mineral density will take place for children with FMF at attack free periods and for control group at periods that they are completely healthy. The maximun duration of the above control will be 24 hours.</time_frame>
      <description>This study will include 62 children, 31 healthy and 31 with FMF.&#xD;
  All children will undergo:&#xD;
  1. Blood examination that will include check of calcium metabolism, Vitamin D levels, kidney function, hormonal control, thyroid function control. Biomarkers of the RANK/RANKL/OPG, which have a major role in osteoblast/osteoclast activity, will be tested.&#xD;
  The subjects will be devided according to gender and age: 2 age groups: a) 6-12 years, b) 12 - 20 years.&#xD;
  All the parameters will be compared to check if there is statistically significant difference between healthy children and children with FMF.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Effect of chronic inflammation of FMF on bone density</measure>
      <time_frame>The evaluation of bone mineral density will take place for children with FMF at attack free periods and for control group at periods that they are completely healthy. The maximun duration of the above control will be 24 hours.</time_frame>
      <description>All children will undergo:&#xD;
  2. Bone density measurment by Dual Energy X-ray Absorptiometry (the most reliable method for imaging bone density and with the minimum radiation). We will check z-score of Lumbar spine and z-score of Total Body Less Head.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Effect of obesity on chronic inflammation of FMF</measure>
      <time_frame>The evaluation of bone mineral density will take place for children with FMF at attack free periods and for control group at periods that they are completely healthy. The maximun duration of the above control will be 24 hours.</time_frame>
      <description>We will measure Body Mass Index (BMI) in all subjects. We will measure weight in kilograms (kg) and height in meters (m) to arrive at one reported value of BMI in kg/m^2.</description>
    </primary_outcome>
    <number_of_groups>2</number_of_groups>
    <enrollment type="Anticipated">62</enrollment>
    <condition>Familial Mediterranean Fever</condition>
    <arm_group>
      <arm_group_label>Patients</arm_group_label>
      <description>32 patients with Familial mediterranenan fever will participate. In these patients we will check bone mineral density using the dexa method.&#xD;
  Blood tests will also be taken to assess calcium metabolism. All patients will be treated with colchicine.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Control group</arm_group_label>
      <description>Healthy children will be used as control group. MEFV gene will be checked to exclude diagnosis of FMF. In these patients we will check bone mineral density using the dexa method. Blood tests will also be taken to assess calcium metabolism. The results from the two groups will be compared.</description>
    </arm_group>
    <biospec_retention>Samples With DNA</biospec_retention>
    <biospec_descr>
      <textblock>
        Blood samples will be tested for MEFV.&#xD;
      </textblock>
    </biospec_descr>
    <eligibility>
      <study_pop>
        <textblock>
          Two groups will be used: patients and control group. The results from blood examination and&#xD;
          DEXA will be compared in order to check differences in bone mineral density betwwen the two&#xD;
          groups.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  For patients:&#xD;
  &#xD;
                 -  Age &gt; 6 years&#xD;
  &#xD;
                 -  BMI 3rd - 90th percentile&#xD;
  &#xD;
                 -  Meet the Tel Hashomer criteria (Avi Linhnen 1997)&#xD;
  &#xD;
                 -  Confirmed diagnosis by finding mutation(s) in the MEFV gene&#xD;
  &#xD;
                 -  Taking medication (colchicine) for at least 3 months&#xD;
  &#xD;
                 -  Normal physical activity during the last month, according to the questionnaire&#xD;
                    that will be distributed&#xD;
  &#xD;
                 -  Free individual history for bone diseases&#xD;
  &#xD;
                 -  Normal thyroid function&#xD;
  &#xD;
            -  For the control group:&#xD;
  &#xD;
                 -  Age &gt; 6 years&#xD;
  &#xD;
                 -  BMI 3rd - 90th percentile&#xD;
  &#xD;
                 -  Free individual history for bone diseases&#xD;
  &#xD;
                 -  Normal physical activity according to the questionnaire&#xD;
  &#xD;
                 -  Normal thyroid function&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  For patients:&#xD;
  &#xD;
                 -  Age &lt; 6 years&#xD;
  &#xD;
                 -  BMI &lt; 3rd or &gt; 90th percentile&#xD;
  &#xD;
                 -  Period of attack period of the disease&#xD;
  &#xD;
                 -  Those who have not started treatment with colchicine&#xD;
  &#xD;
                 -  Those who do not adapt well to taking colchicine&#xD;
  &#xD;
                 -  Decreased physical activity during the last month according to the questionnaire&#xD;
  &#xD;
                 -  Finding from the history of bone diseases that could affect the results&#xD;
  &#xD;
                 -  Taking vitamins that could affect the results&#xD;
  &#xD;
                 -  Existence of a factor that does not allow the performance of Dexa (when for&#xD;
                    example the safe and appropriate placement of the child cannot be ensured)&#xD;
  &#xD;
                 -  History of previous surgery which forced the patient to be bedridden for a&#xD;
                    significant period of time. Possible unreliable result of bone mineral density&#xD;
                    measurement due to reduced physical activity.&#xD;
  &#xD;
            -  For the control group:&#xD;
  &#xD;
                 -  Age &lt; 6 years&#xD;
  &#xD;
                 -  BMI &lt; 3rd or &gt; 90th percentile&#xD;
  &#xD;
                 -  Taking vitamins that could affect the results&#xD;
  &#xD;
                 -  Decreased physical activity during the last month according to the questionnaire&#xD;
  &#xD;
                 -  History of previous surgery in the last year&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>6 Years</minimum_age>
      <maximum_age>20 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Maria Fotoulaki, Professor</last_name>
      <role>Study Chair</role>
      <affiliation>Papageorgiou General Hospital</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Effimia Papadopoulou, Professor</last_name>
      <role>Study Director</role>
      <affiliation>Papageorgiou General Hospital</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Christina Chaintari, Pediatrician</last_name>
      <role>Principal Investigator</role>
      <affiliation>Papageorgiou General Hospital</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Assimina Galli, Professor</last_name>
      <role>Study Chair</role>
      <affiliation>AHEPA General Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Christina Chaintari, Pediatrician</last_name>
      <phone>6970680667</phone>
      <email>christinachaintari@gmail.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Effimia Papadopoulou, Professor</last_name>
      <phone>6977813869</phone>
      <email>papadoef@auth.gr</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Papageorgiou General Hospital</name>
        <address>
          <city>Thessaloníki</city>
          <state>Municipality Of Pavlou Mela</state>
          <zip>56403</zip>
          <country>Greece</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Christina Chaintari, Pediatrician</last_name>
        <phone>6970680667</phone>
        <email>christinachaintari@gmail.com</email>
      </contact>
      <contact_backup>
        <last_name>Effimia Papadopoulou, Professor</last_name>
        <phone>6977813869</phone>
        <email>papadoef@auth.gr</email>
      </contact_backup>
    </location>
    <location_countries>
      <country>Greece</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>June 5, 2023</study_first_submitted>
    <study_first_submitted_qc>September 11, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 13, 2023</study_first_posted>
    <last_update_submitted>September 11, 2023</last_update_submitted>
    <last_update_submitted_qc>September 11, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 13, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Familial Mediterranean Fever</keyword>
    <keyword>Bone mineral density</keyword>
    <keyword>Low vitamin D</keyword>
    <keyword>DEXA</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Brucellosis</mesh_term>
      <mesh_term>Familial Mediterranean Fever</mesh_term>
      <mesh_term>Hereditary Autoinflammatory Diseases</mesh_term>
      <mesh_term>Fever</mesh_term>
    </condition_browse>
    <!-- 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/NCT06034795
  org study id: q3e689cu
  nct id: NCT06034795
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Familial Mediterranean Fever is a chronic auto-inflammatory disease. In the context of
        chronic inflammation, it seems that, among others, it also affects bone density in children.
        Bone loss may be due to subclinical inflammation that persists even during periods of
        remission. In addition, inflammatory cytokines also play an important role (mainly during
        episodes) resulting in an increase in bone degradation and ultimately a reduction in bone
        mass. Cytokines mainly associated with bone degradation and osteoclast activity are: IL-1R,
        IL-2, IL-6, IL-8, TNFa.
  
        The purpose of this study is to determine the effect of FMF on bone density and to compare
        the results with a healthy population. In addition, the difference between the children with
        FMF will be studied according to the mutation they carry.
  For the above purpose, 62 children will participate, 31 healthy and 31 with FMF(confirmed
        mutation/s in the MEFV (Marenostrin Encoding Fever Gene) ).
  
        They will be separated based on gender (boys, girls) and age: 2 age groups: a) 6-12 years, b)
        12 - 20 years, separation into pre-adolescent children and adolescents (according to Tanner)
        and Body Mass Index ( BMI) (3rd-90th ED). Of the 31 children with FMF, all will be treated
        with colchicine and the study will not take place during periods of disease attack.
  
        An attack free period is defined as a period of at least 3 weeks without clinical symptoms
        (fever, abdominal pain, arthritis) and without acute phase indicators (increased CRP, TKE,
        WBC).
  
        The healthy population will exclude children with a history of disease related to a bone
        disorder. In addition, the existence of other factors that could affect bone density will be
        investigated in all 62 children. For this reason, there will be a check of calcium
        metabolism, vitamin D, kidney function, hormonal check, thyroid function check. Biomarkers of
        the RANK/RANKL/OPG axis that have a major role in osteoblast/osteoclast activity will be
        tested. Children's physical activity will be also assessed.
  
        Bone density measurement will be done with a Hologic DISCOVERY QDR DXA (Dual Energy X-ray
        Absorptiometry) machine, the "gold standard" for spine and hip bone disorder screening
        worldwide. The program to be implemented will be adapted to childhood.
  
        Then the following will be assessed: Body Mineral Density (BMD), Body Mineral Content (BMC)
        and z-score for the vertebrae of the OMSS (O1-O4) and Total Body less Head (TBLH).
  observational model: Case-Control
  time perspective: Prospective
  measure: Effect of chronic inflammation of FMF on bone metabolism
  time frame: The evaluation of bone mineral density will take place for children with FMF at attack free periods and for control group at periods that they are completely healthy. The maximun duration of the above control will be 24 hours.
  description: This study will include 62 children, 31 healthy and 31 with FMF.
  All children will undergo:
  1. Blood examination that will include check of calcium metabolism, Vitamin D levels, kidney function, hormonal control, thyroid function control. Biomarkers of the RANK/RANKL/OPG, which have a major role in osteoblast/osteoclast activity, will be tested.
  The subjects will be devided according to gender and age: 2 age groups: a) 6-12 years, b) 12 - 20 years.
  All the parameters will be compared to check if there is statistically significant difference between healthy children and children with FMF.
  measure: Effect of chronic inflammation of FMF on bone density
  time frame: The evaluation of bone mineral density will take place for children with FMF at attack free periods and for control group at periods that they are completely healthy. The maximun duration of the above control will be 24 hours.
  description: All children will undergo:
  2. Bone density measurment by Dual Energy X-ray Absorptiometry (the most reliable method for imaging bone density and with the minimum radiation). We will check z-score of Lumbar spine and z-score of Total Body Less Head.
  measure: Effect of obesity on chronic inflammation of FMF
  time frame: The evaluation of bone mineral density will take place for children with FMF at attack free periods and for control group at periods that they are completely healthy. The maximun duration of the above control will be 24 hours.
  description: We will measure Body Mass Index (BMI) in all subjects. We will measure weight in kilograms (kg) and height in meters (m) to arrive at one reported value of BMI in kg/m^2.
  arm group label: Patients
  description: 32 patients with Familial mediterranenan fever will participate. In these patients we will check bone mineral density using the dexa method.
  Blood tests will also be taken to assess calcium metabolism. All patients will be treated with colchicine.
  arm group label: Control group
  description: Healthy children will be used as control group. MEFV gene will be checked to exclude diagnosis of FMF. In these patients we will check bone mineral density using the dexa method. Blood tests will also be taken to assess calcium metabolism. The results from the two groups will be compared.
  Blood samples will be tested for MEFV.
  study pop: 
  sampling method: Probability Sample
  criteria: 
  gender: All
  minimum age: 6 Years
  maximum age: 20 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Maria Fotoulaki, Professor
  role: Study Chair
  affiliation: Papageorgiou General Hospital
  last name: Effimia Papadopoulou, Professor
  role: Study Director
  affiliation: Papageorgiou General Hospital
  last name: Christina Chaintari, Pediatrician
  role: Principal Investigator
  affiliation: Papageorgiou General Hospital
  last name: Assimina Galli, Professor
  role: Study Chair
  affiliation: AHEPA General Hospital
  last name: Christina Chaintari, Pediatrician
  phone: 6970680667
  email: christinachaintari@gmail.com
  last name: Effimia Papadopoulou, Professor
  phone: 6977813869
  email: papadoef@auth.gr
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  country: Greece
  responsible party type: Sponsor
  mesh term: Brucellosis
  mesh term: Familial Mediterranean Fever
  mesh term: Hereditary Autoinflammatory Diseases
  mesh term: Fever