<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/NCT03297775</url>
  </required_header>
  <id_info>
    <org_study_id>16-1097</org_study_id>
    <nct_id>NCT03297775</nct_id>
  </id_info>
  <brief_title>Rheumatoid Arthritis Patients at Risk for Interstitial Lung Disease</brief_title>
  <acronym>RAPID</acronym>
  <official_title>Rheumatoid Arthritis Patients at Risk for Interstitial Lung Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Colorado, Denver</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Colorado, Denver</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 overall goal of this study is to define the phenotype of Interstitial Lung Disease (ILD),&#xD;
      and identify factors that predict radiologic progression in those with subclinical RA-ILD, in&#xD;
      patients with rheumatoid arthritis (RA). The investigators hypothesize that there are common&#xD;
      core elements (e.g. clinical features, genetic variants, and/or biologic markers) between&#xD;
      other forms of ILD (e.g. idiopathic pulmonary fibrosis, IPF) and subclinical RA-ILD that&#xD;
      places individuals at risk for the development of lung disease.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 22, 2017</start_date>
  <completion_date type="Anticipated">June 2027</completion_date>
  <primary_completion_date type="Anticipated">June 2027</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>5 Years</target_duration>
  <primary_outcome>
    <measure>Presence of interstitial lung disease on high resolution CT (HRCT) chest imaging</measure>
    <time_frame>3-5 years</time_frame>
    <description>HRCT scans of the chest will be interpreted by two radiologists and the presence or absence of interstitial lung abnormality will be recorded. When present, abnormalities will be categorized as absent, equivocal, non-fibrotic, or fibrotic, and the extent of any reticular abnormalities will be graded on an 11-point scale (0, 1-10%, 11-20%, etc.). Additionally, the presence or absence of airway disease, centrilobular thickening, mosaic attenuation, and air trapping will be recorded.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression of lung disease over time</measure>
    <time_frame>3-5 Years</time_frame>
    <description>Radiologic progression of lung disease will be determined through a comparison of baseline HRCT chest findings to follow-up HRCT chest findings at the 3-5 year follow-up benchmark. Similar to baseline, follow-up HRCT scans of the chest will be interpreted by 2 different radiologists. Quantitative radiologic progression will be defined as ≥ 10% increase in fibrotic changes from baseline to follow-up - additionally, the percent reticular change, percent honeycomb change, and percent traction bronchiectasis on the follow-up scan will be quantified and recorded.&#xD;
Radiologic findings of progression will be used in correlation with other clinical features to determine the clinical relevance of the change. The clinical features include - change in cough, change in dyspnea (as measured by UCSD shortness of breath questionnaire), change in FVC percent predicted value, the development of established RA-ILD, or respiratory-related death, over the same time period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Impact of subclinical RA-ILD on health-related quality of life in RA</measure>
    <time_frame>3-5 Years</time_frame>
    <description>The impact of subclinical RA-ILD on health-related quality of life will be measured using subjective patient questionnaires that will be completed at both baseline and follow-up. These questionnaires include - SF-36, St. George Respiratory Questionnaire, and Multi-Dimensional Health Assessment Questionnaire.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Outcome of airways disease</measure>
    <time_frame>3-5 Years</time_frame>
    <description>Clinical outcomes will be measured through respiratory assessment (physical exam), changes is dyspnea (based on the University of California San Diego shortness of breath questionnaire), changes in FVC percent predicted values (based on pulmonary function testing), increase in cough (determined using a visual analog scale, where 10 is the worst cough and 0 is no cough), and development of RA-ILD requiring treatment.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">750</enrollment>
  <condition>Rheumatoid Arthritis</condition>
  <condition>Interstitial Lung Disease</condition>
  <arm_group>
    <arm_group_label>RA with Sub-clinical ILD</arm_group_label>
    <description>Subjects will be followed annually until study closure.&#xD;
Assessments are as follows:&#xD;
Clinical (Annual): Demographics, health-related behaviors, co-morbidities, medications, respiratory symptoms, rheumatologic assessment, quality of life&#xD;
Physiologic (3-5 yrs FU): Lung function on Pulmonary Function Test (PFT)&#xD;
Radiologic (3-5 yrs FU): HRCT scan of chest&#xD;
Genetic (3-5 yrs FU): Blood sample collection for RNA&#xD;
Biologic (3-5 yrs FU): Blood sample collection for other blood markers</description>
  </arm_group>
  <arm_group>
    <arm_group_label>RA with No-ILD</arm_group_label>
    <description>Subjects will be followed annually until study closure.&#xD;
Assessments are as follows:&#xD;
Clinical (Annual): Demographics, health-related behaviors, co-morbidities, medications, respiratory symptoms, rheumatologic assessment, quality of life&#xD;
Physiologic (3-5 yrs FU): Lung function on Pulmonary Function Test (PFT)&#xD;
Radiologic (3-5 yrs FU): HRCT scan of chest&#xD;
Genetic (3-5 yrs FU): Blood sample collection for RNA&#xD;
Biologic (3-5 yrs FU): Blood sample collection for other blood markers&#xD;
Note: Certain follow-up procedures may not occur for every subject and will be determined by the research team.</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      The following bio-specimens will be collected at baseline and at 3-5 years follow-up:&#xD;
&#xD;
        -  DNA (baseline only)&#xD;
&#xD;
        -  RNA&#xD;
&#xD;
        -  PBMC, Serum, Plasma&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Subjects are selected for participation in the study because they have an active diagnosis&#xD;
        of rheumatoid arthritis and are at risk for the development of lung disease.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. ≥ 45years old&#xD;
&#xD;
          2. Diagnosis of RA using the 2010 American College of Rheumatology (ACR) criteria&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Inability to give informed consent&#xD;
&#xD;
          2. Pregnant women&#xD;
&#xD;
          3. History of interstitial lung disease&#xD;
&#xD;
          4. Evidence of other causes of diffuse parenchymal lung disease such as infection, drug&#xD;
             toxicity, other autoimmune processes, etc.&#xD;
&#xD;
          5. Subjects over the age of 90 years old or less than 45 years old&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>45 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joyce S Lee, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Colorado, Denver</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Haylie A Lengel</last_name>
    <phone>970-376-8303</phone>
    <email>haylie.lengel@cuanschutz.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Joyce S Lee, MD</last_name>
    <phone>303-724-6109</phone>
    <email>joyce.lee@ucdenver.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of Colorado - Anschutz Medical Campus</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Haylie A Lengel</last_name>
      <phone>970-376-8303</phone>
      <email>haylie.lengel@cuanschutz.edu</email>
    </contact>
    <investigator>
      <last_name>Joce Lee, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Kristen Demoruelle, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jason Kolfenbach, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Duane Pearson, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Kevin Deane, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>September 19, 2017</study_first_submitted>
  <study_first_submitted_qc>September 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 29, 2017</study_first_posted>
  <last_update_submitted>October 6, 2022</last_update_submitted>
  <last_update_submitted_qc>October 6, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 12, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Rheumatoid Arthritis</keyword>
  <keyword>RA</keyword>
  <keyword>Interstitial Lung Disease</keyword>
  <keyword>ILD</keyword>
  <keyword>lung disease</keyword>
  <keyword>connective tissue disease</keyword>
  <keyword>CTD</keyword>
  <keyword>idiopathic pulmonary fibrosis</keyword>
  <keyword>IPF</keyword>
  <keyword>airways disease</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>
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Lung Diseases, Interstitial</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/NCT03297775
org study id: 16-1097
nct id: NCT03297775
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The overall goal of this study is to define the phenotype of Interstitial Lung Disease (ILD),
      and identify factors that predict radiologic progression in those with subclinical RA-ILD, in
      patients with rheumatoid arthritis (RA). The investigators hypothesize that there are common
      core elements (e.g. clinical features, genetic variants, and/or biologic markers) between
      other forms of ILD (e.g. idiopathic pulmonary fibrosis, IPF) and subclinical RA-ILD that
      places individuals at risk for the development of lung disease.
observational model: Cohort
time perspective: Prospective
measure: Presence of interstitial lung disease on high resolution CT (HRCT) chest imaging
time frame: 3-5 years
description: HRCT scans of the chest will be interpreted by two radiologists and the presence or absence of interstitial lung abnormality will be recorded. When present, abnormalities will be categorized as absent, equivocal, non-fibrotic, or fibrotic, and the extent of any reticular abnormalities will be graded on an 11-point scale (0, 1-10%, 11-20%, etc.). Additionally, the presence or absence of airway disease, centrilobular thickening, mosaic attenuation, and air trapping will be recorded.
measure: Progression of lung disease over time
time frame: 3-5 Years
description: Radiologic progression of lung disease will be determined through a comparison of baseline HRCT chest findings to follow-up HRCT chest findings at the 3-5 year follow-up benchmark. Similar to baseline, follow-up HRCT scans of the chest will be interpreted by 2 different radiologists. Quantitative radiologic progression will be defined as ≥ 10% increase in fibrotic changes from baseline to follow-up - additionally, the percent reticular change, percent honeycomb change, and percent traction bronchiectasis on the follow-up scan will be quantified and recorded.
Radiologic findings of progression will be used in correlation with other clinical features to determine the clinical relevance of the change. The clinical features include - change in cough, change in dyspnea (as measured by UCSD shortness of breath questionnaire), change in FVC percent predicted value, the development of established RA-ILD, or respiratory-related death, over the same time period.
measure: Impact of subclinical RA-ILD on health-related quality of life in RA
time frame: 3-5 Years
description: The impact of subclinical RA-ILD on health-related quality of life will be measured using subjective patient questionnaires that will be completed at both baseline and follow-up. These questionnaires include - SF-36, St. George Respiratory Questionnaire, and Multi-Dimensional Health Assessment Questionnaire.
measure: Outcome of airways disease
time frame: 3-5 Years
description: Clinical outcomes will be measured through respiratory assessment (physical exam), changes is dyspnea (based on the University of California San Diego shortness of breath questionnaire), changes in FVC percent predicted values (based on pulmonary function testing), increase in cough (determined using a visual analog scale, where 10 is the worst cough and 0 is no cough), and development of RA-ILD requiring treatment.
arm group label: RA with Sub-clinical ILD
description: Subjects will be followed annually until study closure.
Assessments are as follows:
Clinical (Annual): Demographics, health-related behaviors, co-morbidities, medications, respiratory symptoms, rheumatologic assessment, quality of life
Physiologic (3-5 yrs FU): Lung function on Pulmonary Function Test (PFT)
Radiologic (3-5 yrs FU): HRCT scan of chest
Genetic (3-5 yrs FU): Blood sample collection for RNA
Biologic (3-5 yrs FU): Blood sample collection for other blood markers
arm group label: RA with No-ILD
description: Subjects will be followed annually until study closure.
Assessments are as follows:
Clinical (Annual): Demographics, health-related behaviors, co-morbidities, medications, respiratory symptoms, rheumatologic assessment, quality of life
Physiologic (3-5 yrs FU): Lung function on Pulmonary Function Test (PFT)
Radiologic (3-5 yrs FU): HRCT scan of chest
Genetic (3-5 yrs FU): Blood sample collection for RNA
Biologic (3-5 yrs FU): Blood sample collection for other blood markers
Note: Certain follow-up procedures may not occur for every subject and will be determined by the research team.
The following bio-specimens will be collected at baseline and at 3-5 years follow-up:

        -  DNA (baseline only)

        -  RNA

        -  PBMC, Serum, Plasma
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 45 Years
maximum age: 90 Years
healthy volunteers: No
last name: Joyce S Lee, MD
role: Principal Investigator
affiliation: University of Colorado, Denver
last name: Haylie A Lengel
phone: 970-376-8303
email: haylie.lengel@cuanschutz.edu
last name: Joyce S Lee, MD
phone: 303-724-6109
email: joyce.lee@ucdenver.edu
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Arthritis
mesh term: Arthritis, Rheumatoid
mesh term: Lung Diseases
mesh term: Lung Diseases, Interstitial
sharing ipd: No