<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/NCT04486027</url>
  </required_header>
  <id_info>
    <org_study_id>2017/900/19</org_study_id>
    <nct_id>NCT04486027</nct_id>
  </id_info>
  <brief_title>Can Cytokines be Used as an Activation Marker</brief_title>
  <official_title>Can Cytokines be Used as an Activation Marker in Rheumatoid Arthritis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Maltepe University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Maltepe University</source>
  <oversight_info>
    <has_dmc>Yes</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>
      RA is a chronic, autoimmune, inflammatory disease that involves small joints in the form of&#xD;
      symmetrical polyarthritis and progresses with exacerbations and remissions. Pain, swelling,&#xD;
      tenderness and morning stiffness are typical of the joints involved. Although it is&#xD;
      approached as a primary joint disease, a wide variety of extra-articular involvements may&#xD;
      also occur. In this cross sectional study sedimentation rate (ESR), C- Reactive protein&#xD;
      (CRP), Tumor necrosis factor (TNF)-α, soluble-TNF-α receptor (TNF-R), Interleukin (IL)-1B and&#xD;
      IL-10 were measured in three groups which were healthy volunteers, patients with RA in active&#xD;
      period, and patients with RA in remission.&#xD;
&#xD;
      TNF-R can be the main pathophysiological factor and a marker showing activation. TNF-R can be&#xD;
      very important in revealing the effect of TNF on the disease and the value of this effect in&#xD;
      the treatment and ensuring the follow-up of the disease with CRP instead of ESR in&#xD;
      activation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Aims: The etiopathogenesis of Rheumatoid Arthritis (RA) is not clearly understood. However,&#xD;
      role of the cytokines takes an important part of this mechanism. The investigators aimed to&#xD;
      bring a new approach to the concept of 'remission' in patients with RA.&#xD;
&#xD;
      Background: RA is a chronic, autoimmune, inflammatory disease that involves small joints in&#xD;
      the form of symmetrical polyarthritis and progresses with exacerbations and remissions. Pain,&#xD;
      swelling, tenderness and morning stiffness are typical of the joints involved. Although it is&#xD;
      approached as a primary joint disease, a wide variety of extra-articular involvements may&#xD;
      also occur. It is an interesting pathophysiological process, the exact cause of which is&#xD;
      still unknown, with many environmental, genetic and potentially undiscovered possible factors&#xD;
      in a chaotic manner.&#xD;
&#xD;
      Objective: In this prospective study, sedimentation rate (ESR), C- Reactive protein (CRP),&#xD;
      Tumor necrosis factor (TNF)-α, soluble-TNF-α receptor (TNF-R), Interleukin (IL)-1B and IL-10&#xD;
      were measured in three groups which were healthy volunteers, patients with RA in active&#xD;
      period, and patients with RA in remission. Disease activity score-28 (DAS-28) was calculated&#xD;
      in active RA and RA in remission.&#xD;
&#xD;
      Methods: This study included 20 healthy volunteers, 20 remission patients with RA and 20&#xD;
      active RA patients. Venous blood samples were collected from patients in both healthy and RA&#xD;
      groups.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 5, 2017</start_date>
  <completion_date type="Actual">December 15, 2018</completion_date>
  <primary_completion_date type="Actual">June 1, 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>C Reactive Protein</measure>
    <time_frame>up to 24 months</time_frame>
    <description>Inflammatory biomarker</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Erythrocyte sedimentation rate</measure>
    <time_frame>up to 24 months</time_frame>
    <description>Inflammatory biomarker</description>
  </primary_outcome>
  <primary_outcome>
    <measure>TNF alpha</measure>
    <time_frame>up to 24 months</time_frame>
    <description>Cytokine</description>
  </primary_outcome>
  <primary_outcome>
    <measure>DAS 28</measure>
    <time_frame>up to 24 months</time_frame>
    <description>Disease activity scores</description>
  </primary_outcome>
  <primary_outcome>
    <measure>IL 1beta</measure>
    <time_frame>up to 24 months</time_frame>
    <description>Cytokine</description>
  </primary_outcome>
  <primary_outcome>
    <measure>IL 10</measure>
    <time_frame>up to 24 months</time_frame>
    <description>Cytokine</description>
  </primary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">60</enrollment>
  <condition>Rheumatoid Arthritis</condition>
  <arm_group>
    <arm_group_label>Healthy</arm_group_label>
    <description>Healthy individuals not smoking, not using Disease-Modifying Anti-Rheumatic Drugs (DMARD) and/or anti-inflammatory drugs other than cortisol and methotrexate, not receiving chemotherapy, not being hypothyroidic</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Active Rheumatoid Arthritis</arm_group_label>
    <description>Active Rheumatoid Arthritis meeting American College of Rheumatology (ACR) RA remission criteria</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Rheumatoid Arthritis in remission</arm_group_label>
    <description>Rheumatoid Arthritis in remission meeting American College of Rheumatology (ACR) RA remission criteria</description>
  </arm_group>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Serum&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        This study included 20 healthy volunteers, 20 remission patients with RA and 20 active&#xD;
        patients with RA. Patients who met the study criteria among patients with RA who applied to&#xD;
        Maltepe University Medical Faculty Hospital Internal Medicine-Rheumatology Outpatient&#xD;
        Clinic were included in the study&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Healthy individuals and Rheumatoid Arthritis patients meeting American College of&#xD;
        Rheumatology (ACR) RA remission criteria.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Smoking, Using Disease-Modifying Anti-Rheumatic Drugs (DMARD) and/or anti-inflammatory&#xD;
        drugs other than cortisol and methotrexate, Receiving chemotherapy, Being hypothyroid&#xD;
&#xD;
        -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Selim Nalbant, Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>Maltepe University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Selim Nalbant</name>
      <address>
        <city>Istanbul</city>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Turkey</country>
  </location_countries>
  <reference>
    <citation>Malmstrom V, Catrina AI, Klareskog L. The immunopathogenesis of seropositive rheumatoid arthritis: from triggering to targeting. Nat Rev Immunol. 2017 Jan;17(1):60-75. doi: 10.1038/nri.2016.124. Epub 2016 Dec 5. Erratum In: Nat Rev Immunol. 2022 Jul;22(7):459.</citation>
    <PMID>27916980</PMID>
  </reference>
  <reference>
    <citation>Deane KD, O'Donnell CI, Hueber W, Majka DS, Lazar AA, Derber LA, Gilliland WR, Edison JD, Norris JM, Robinson WH, Holers VM. The number of elevated cytokines and chemokines in preclinical seropositive rheumatoid arthritis predicts time to diagnosis in an age-dependent manner. Arthritis Rheum. 2010 Nov;62(11):3161-72. doi: 10.1002/art.27638.</citation>
    <PMID>20597112</PMID>
  </reference>
  <reference>
    <citation>Pratt AG, Isaacs JD. Seronegative rheumatoid arthritis: pathogenetic and therapeutic aspects. Best Pract Res Clin Rheumatol. 2014 Aug;28(4):651-9. doi: 10.1016/j.berh.2014.10.016. Epub 2014 Nov 18.</citation>
    <PMID>25481556</PMID>
  </reference>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 13, 2020</study_first_submitted>
  <study_first_submitted_qc>July 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 2020</study_first_posted>
  <last_update_submitted>July 21, 2020</last_update_submitted>
  <last_update_submitted_qc>July 21, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 24, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Maltepe University</investigator_affiliation>
    <investigator_full_name>Selim Nalbant</investigator_full_name>
    <investigator_title>Prof</investigator_title>
  </responsible_party>
  <keyword>c reactive protein</keyword>
  <keyword>Erythrocyte sedimentation rate</keyword>
  <keyword>DAS-28</keyword>
  <keyword>Rheumatoid Arthritis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Arthritis</mesh_term>
    <mesh_term>Arthritis, Rheumatoid</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/NCT04486027
org study id: 2017/900/19
nct id: NCT04486027
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
RA is a chronic, autoimmune, inflammatory disease that involves small joints in the form of
      symmetrical polyarthritis and progresses with exacerbations and remissions. Pain, swelling,
      tenderness and morning stiffness are typical of the joints involved. Although it is
      approached as a primary joint disease, a wide variety of extra-articular involvements may
      also occur. In this cross sectional study sedimentation rate (ESR), C- Reactive protein
      (CRP), Tumor necrosis factor (TNF)-α, soluble-TNF-α receptor (TNF-R), Interleukin (IL)-1B and
      IL-10 were measured in three groups which were healthy volunteers, patients with RA in active
      period, and patients with RA in remission.

      TNF-R can be the main pathophysiological factor and a marker showing activation. TNF-R can be
      very important in revealing the effect of TNF on the disease and the value of this effect in
      the treatment and ensuring the follow-up of the disease with CRP instead of ESR in
      activation.
Aims: The etiopathogenesis of Rheumatoid Arthritis (RA) is not clearly understood. However,
      role of the cytokines takes an important part of this mechanism. The investigators aimed to
      bring a new approach to the concept of 'remission' in patients with RA.

      Background: RA is a chronic, autoimmune, inflammatory disease that involves small joints in
      the form of symmetrical polyarthritis and progresses with exacerbations and remissions. Pain,
      swelling, tenderness and morning stiffness are typical of the joints involved. Although it is
      approached as a primary joint disease, a wide variety of extra-articular involvements may
      also occur. It is an interesting pathophysiological process, the exact cause of which is
      still unknown, with many environmental, genetic and potentially undiscovered possible factors
      in a chaotic manner.

      Objective: In this prospective study, sedimentation rate (ESR), C- Reactive protein (CRP),
      Tumor necrosis factor (TNF)-α, soluble-TNF-α receptor (TNF-R), Interleukin (IL)-1B and IL-10
      were measured in three groups which were healthy volunteers, patients with RA in active
      period, and patients with RA in remission. Disease activity score-28 (DAS-28) was calculated
      in active RA and RA in remission.

      Methods: This study included 20 healthy volunteers, 20 remission patients with RA and 20
      active RA patients. Venous blood samples were collected from patients in both healthy and RA
      groups.
observational model: Case-Control
time perspective: Cross-Sectional
measure: C Reactive Protein
time frame: up to 24 months
description: Inflammatory biomarker
measure: Erythrocyte sedimentation rate
time frame: up to 24 months
description: Inflammatory biomarker
measure: TNF alpha
time frame: up to 24 months
description: Cytokine
measure: DAS 28
time frame: up to 24 months
description: Disease activity scores
measure: IL 1beta
time frame: up to 24 months
description: Cytokine
measure: IL 10
time frame: up to 24 months
description: Cytokine
arm group label: Healthy
description: Healthy individuals not smoking, not using Disease-Modifying Anti-Rheumatic Drugs (DMARD) and/or anti-inflammatory drugs other than cortisol and methotrexate, not receiving chemotherapy, not being hypothyroidic
arm group label: Active Rheumatoid Arthritis
description: Active Rheumatoid Arthritis meeting American College of Rheumatology (ACR) RA remission criteria
arm group label: Rheumatoid Arthritis in remission
description: Rheumatoid Arthritis in remission meeting American College of Rheumatology (ACR) RA remission criteria
Serum
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Selim Nalbant, Prof
role: Principal Investigator
affiliation: Maltepe University
facility: 
country: Turkey
citation: Malmstrom V, Catrina AI, Klareskog L. The immunopathogenesis of seropositive rheumatoid arthritis: from triggering to targeting. Nat Rev Immunol. 2017 Jan;17(1):60-75. doi: 10.1038/nri.2016.124. Epub 2016 Dec 5. Erratum In: Nat Rev Immunol. 2022 Jul;22(7):459.
PMID: 27916980
citation: Deane KD, O'Donnell CI, Hueber W, Majka DS, Lazar AA, Derber LA, Gilliland WR, Edison JD, Norris JM, Robinson WH, Holers VM. The number of elevated cytokines and chemokines in preclinical seropositive rheumatoid arthritis predicts time to diagnosis in an age-dependent manner. Arthritis Rheum. 2010 Nov;62(11):3161-72. doi: 10.1002/art.27638.
PMID: 20597112
citation: Pratt AG, Isaacs JD. Seronegative rheumatoid arthritis: pathogenetic and therapeutic aspects. Best Pract Res Clin Rheumatol. 2014 Aug;28(4):651-9. doi: 10.1016/j.berh.2014.10.016. Epub 2014 Nov 18.
PMID: 25481556
responsible party type: Principal Investigator
investigator affiliation: Maltepe University
investigator full name: Selim Nalbant
investigator title: Prof
mesh term: Arthritis
mesh term: Arthritis, Rheumatoid
sharing ipd: No