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/NCT05981885</url>
    </required_header>
    <id_info>
      <org_study_id>202100802</org_study_id>
      <nct_id>NCT05981885</nct_id>
    </id_info>
    <brief_title>68Ga-FAPI PET/CT to Detect Ongoing Fibroblast Activity in Post-acute COVID-19</brief_title>
    <acronym>FAPI CLIMATE</acronym>
    <official_title>68Ga-FAPI PET/CT to Detect Ongoing Fibroblast Activity in Post-acute COVID-19 With Respiratory Impairment After Hospital Discharge</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University Medical Center Groningen</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>ZonMw: The Netherlands Organisation for Health Research and Development</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>University Medical Center Groningen</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 goal of this observational study is to investigate the role fibroblasts play in the&#xD;
        persistent respiratory complaints after a COVID-19 infection. Fibroblasts are involved in&#xD;
        tissue remodeling and repair by creating scar-tissue (fibrosis) after tissue damage has&#xD;
        occurred. The hypothesis is that this process of fibrosis is ongoing in patients with&#xD;
        persistent complaints. To evaluate the roll of fibroblasts a new type of scan is used that is&#xD;
        capable of imaging active fibroblasts, a 68Ga-FAPI PET/CT scan.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Rationale: The pathogenesis of post-acute COVID-19 with respiratory complaints remains&#xD;
        unknown. We aim to explore the pulmonary pattern and fibrosis activity in patients with&#xD;
        post-acute COVID-19 with respiratory complaints using 68Ga-FAPI Positron Emission&#xD;
        Tomography-Computed Tomography (PET/CT) imaging.&#xD;
  &#xD;
        Objective: To relate pulmonary fibroblast activity, measured by FAPI-PET/CT at least 3 months&#xD;
        after hospital discharge, to interstitial lung abnormalities on high resolution CT (HRCT) at&#xD;
        the same time point in post-acute COVID-19 patients with respiratory complaints.&#xD;
  &#xD;
        Study design: This is a ZonMw funded single center prospective observational cohort study of&#xD;
        post-acute COVID-19 patients with respiratory complaints.&#xD;
  &#xD;
        Study population: We will recruit 20 adult patients, all post-ICU or post High-Flow Nasal&#xD;
        Oxygen therapy due to there COVID-19 infection, with post-acute COVID-19 and respiratory&#xD;
        complaints that will undergo 68Ga-FAPI PET/CT imaging to establish pulmonary fibrosis&#xD;
        activity.&#xD;
  &#xD;
        Main study parameters/endpoints: To assess the degree of Fibroblast Activation Protein&#xD;
        expression on 68Ga-FAPI PET/CT at least 3 months after hospital discharge and to relate this&#xD;
        to interstitial lung abnormalities on HRCT at the same time point.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">June 9, 2022</start_date>
    <completion_date type="Anticipated">October 2024</completion_date>
    <primary_completion_date type="Anticipated">October 2023</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>10 Months</target_duration>
    <primary_outcome>
      <measure>Pulmonary SUV values</measure>
      <time_frame>At time of inclusion (T0)</time_frame>
      <description>Based on the FAPI PET/CT scan 3-dimensinal volumes of intrest (VOI) are drawn of high FAPI uptake areas (leasions) and non-uptake areas. Using these VOIs SUV values and metabolic active volume (MAV) can be calculated which then can be used to calculate: total lesion FAPI (TL-FAPI), whole-lung FAPI-MAV (wl FAPI-MAV), wlSUVmean and whole lung TL-FAPI (wlTL-FAPI).</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Correlate biomarkers to pulmonary SUV values</measure>
      <time_frame>At time of inclusion (T0)</time_frame>
      <description>A correlation between the pulmonary FAPI uptake, reported as SUV values (see outcome 1) will be correlated with fibrosis and inflammatory specific biomarkers using Pearson's or Spearman's test.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>6 minute walking test vs pulmonary SUV values</measure>
      <time_frame>At time of inclusion (T0)</time_frame>
      <description>The total walked distance in meters during 6 minutes is correlated with pulmonary FAPI uptake, reported as SUV values (see outcome 1) using Pearson's or Spearman's test.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>DCLO and VC vs pulmonary SUV values</measure>
      <time_frame>At time of inclusion (T0)</time_frame>
      <description>Pulmonary FAPI uptake, reported as SUV values (see outcome 1), will be correlated with DCLO and VC using Pearon's or Spearman's test.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Daily impairments (EQ-5D questionnaire) vs pulmonary SUV values</measure>
      <time_frame>At time of inclusion (T0)</time_frame>
      <description>Pulmonary FAPI uptake, reported as SUV values (see outcome 1), will be correlated with self-reported daily impairments per category as measured by the EQ-5D questionnaire using Pearson's or Spearman's test.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cellular phenotypes</measure>
      <time_frame>At time of inclusion (T0)</time_frame>
      <description>Pulmonary FAPI uptake, reported as SUV values (see outcome 1), will be correlated to systemic and upper respiratory tract cellular phenotypes determined by single cell RNA sequencing using Pearon's or Spearmen's test.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>HRCT</measure>
      <time_frame>At time of inclusion (T0)</time_frame>
      <description>Pulmonary FAPI uptake, reported as SUV values (see outcome 1), will be correlated to HRCT findings: extent of disease (0-100%), reticular pattern (0-100%), portion of groundglass (0-100%), coarness (0-3), honey combing (Yes/No), Distribution groundglass, crazy-paving pattern (Yes/No), fibrosis (Yes/No), Bronchiectasis (Yes/No), Emfyseem (Yes/No) and Pleural effusion (Yes/No).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Follow-up HRCT</measure>
      <time_frame>10 months after T0</time_frame>
      <description>Pulmonary FAPI uptake, reported as SUV values (see outcome 1), will be correlated to HRCT findings in case of persistent respiratory complaints 8-10 months after T0. Findings that are correlated are: extent of disease (0-100%), reticular pattern (0-100%), portion of groundglass (0-100%), coarness (0-3), honey combing (Yes/No), Distribution groundglass, crazy-paving pattern (Yes/No), fibrosis (Yes/No), Bronchiectasis (Yes/No), Emfyseem (Yes/No) and Pleural effusion (Yes/No).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Follow-up daily impairments (EQ-5D questionnaire) vs pulmonary SUV values</measure>
      <time_frame>10 months after T0</time_frame>
      <description>Pulmonary FAPI uptake, reported as SUV values (see outcome 1), will be correlated with self-reported daily impairments per category as measured by the EQ-5D questionnaire using Pearson's or Spearman's test.</description>
    </secondary_outcome>
    <enrollment type="Anticipated">20</enrollment>
    <condition>Post-Acute COVID-19</condition>
    <condition>Post-Acute COVID-19 Infection</condition>
    <condition>Post-Acute COVID-19 Syndrome</condition>
    <condition>Pulmonary Fibrosis</condition>
    <biospec_retention>Samples With DNA</biospec_retention>
    <biospec_descr>
      <textblock>
        Blood and nose epithelium for single cell RNA analysis&#xD;
      </textblock>
    </biospec_descr>
    <eligibility>
      <study_pop>
        <textblock>
          Adults previously admitted to the ICU or ward requiring mechanical ventilation or high flow&#xD;
          nasal oxygen due to their COVID-19 infection with now post-acute COVID-19 and respiratory&#xD;
          complaints.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Male patients &gt;18 years and female patients &gt;20 years discharged from hospital after&#xD;
               PCR-confirmed COVID-19 infection.&#xD;
  &#xD;
            -  Previous ICU or ward admission with high flow nasal oxygen (HFNO) or mechanical&#xD;
               ventilation.&#xD;
  &#xD;
            -  Persistent respiratory complaints (shortness of breath) at least 3 months after&#xD;
               hospital discharge.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Inability or unwilling to give informed consent.&#xD;
  &#xD;
            -  History of claustrophobia or feeling of inability to tolerate supine position for the&#xD;
               PET/CT scans.&#xD;
  &#xD;
            -  Severe or significant comorbidity, defined as COPD GOLD stage II or higher and/or&#xD;
               known interstitial lung disease.&#xD;
  &#xD;
            -  Women who are pregnant or breastfeeding.&#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_official>
      <last_name>Riemer Slart, Prof MD PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>University Medical Center Groningen</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Janesh Pillay, MD PhD</last_name>
      <phone>0625650720</phone>
      <phone_ext>+31</phone_ext>
      <email>j.pillay@umcg.nl</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Bram van Leer, MD</last_name>
      <email>b.van.leer@umcg.nl</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>University Medical Center Groningen</name>
        <address>
          <city>Groningen</city>
          <zip>9713GZ</zip>
          <country>Netherlands</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Riemer Slart, Prof MD PhD</last_name>
        <phone>0625650044</phone>
        <phone_ext>+31</phone_ext>
        <email>r.h.j.a.slart@umcg.nl</email>
      </contact>
      <contact_backup>
        <last_name>Janesh Pillay, MD PhD</last_name>
        <email>j.pillay@umcg.nl</email>
      </contact_backup>
      <investigator>
        <last_name>Bram van Leer, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>Netherlands</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>June 22, 2023</study_first_submitted>
    <study_first_submitted_qc>August 3, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 8, 2023</study_first_posted>
    <last_update_submitted>August 3, 2023</last_update_submitted>
    <last_update_submitted_qc>August 3, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 8, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>68Ga-FAPI-04</keyword>
    <keyword>HRCT</keyword>
    <keyword>Post-ICU</keyword>
    <keyword>Post high-flow Nasal Oxygen therapy</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>COVID-19</mesh_term>
      <mesh_term>Post-Acute COVID-19 Syndrome</mesh_term>
      <mesh_term>Pulmonary Fibrosis</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>Data underlie the results reported in this article will be shared on reasonably request after deidentification of individual participant data. Only investigators whose proposed use of data is for individual participant data meta-analysis and in line with the signed informed consent are eligible for sharing. Proposals should be directed to r.h.j.a.slart@umcg.nl. To gain access, data requestors will need to sign a data access agreement.</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_time_frame>Directly after publication</ipd_time_frame>
      <ipd_access_criteria>Only investigators whose proposed use of data is for individual participant data meta-analysis and in line with the signed informed consent are eligible for sharing</ipd_access_criteria>
    </patient_data>
    <provided_document_section>
      <provided_document>
        <document_type>Study Protocol and Statistical Analysis Plan</document_type>
        <document_has_protocol>Yes</document_has_protocol>
        <document_has_icf>No</document_has_icf>
        <document_has_sap>Yes</document_has_sap>
        <document_date>June 2, 2023</document_date>
        <document_url>https://ClinicalTrials.gov/ProvidedDocs/85/NCT05981885/Prot_SAP_000.pdf</document_url>
      </provided_document>
    </provided_document_section>
    <!-- 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/NCT05981885
  org study id: 202100802
  nct id: NCT05981885
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The goal of this observational study is to investigate the role fibroblasts play in the
        persistent respiratory complaints after a COVID-19 infection. Fibroblasts are involved in
        tissue remodeling and repair by creating scar-tissue (fibrosis) after tissue damage has
        occurred. The hypothesis is that this process of fibrosis is ongoing in patients with
        persistent complaints. To evaluate the roll of fibroblasts a new type of scan is used that is
        capable of imaging active fibroblasts, a 68Ga-FAPI PET/CT scan.
  Rationale: The pathogenesis of post-acute COVID-19 with respiratory complaints remains
        unknown. We aim to explore the pulmonary pattern and fibrosis activity in patients with
        post-acute COVID-19 with respiratory complaints using 68Ga-FAPI Positron Emission
        Tomography-Computed Tomography (PET/CT) imaging.
  
        Objective: To relate pulmonary fibroblast activity, measured by FAPI-PET/CT at least 3 months
        after hospital discharge, to interstitial lung abnormalities on high resolution CT (HRCT) at
        the same time point in post-acute COVID-19 patients with respiratory complaints.
  
        Study design: This is a ZonMw funded single center prospective observational cohort study of
        post-acute COVID-19 patients with respiratory complaints.
  
        Study population: We will recruit 20 adult patients, all post-ICU or post High-Flow Nasal
        Oxygen therapy due to there COVID-19 infection, with post-acute COVID-19 and respiratory
        complaints that will undergo 68Ga-FAPI PET/CT imaging to establish pulmonary fibrosis
        activity.
  
        Main study parameters/endpoints: To assess the degree of Fibroblast Activation Protein
        expression on 68Ga-FAPI PET/CT at least 3 months after hospital discharge and to relate this
        to interstitial lung abnormalities on HRCT at the same time point.
  observational model: Cohort
  time perspective: Prospective
  measure: Pulmonary SUV values
  time frame: At time of inclusion (T0)
  description: Based on the FAPI PET/CT scan 3-dimensinal volumes of intrest (VOI) are drawn of high FAPI uptake areas (leasions) and non-uptake areas. Using these VOIs SUV values and metabolic active volume (MAV) can be calculated which then can be used to calculate: total lesion FAPI (TL-FAPI), whole-lung FAPI-MAV (wl FAPI-MAV), wlSUVmean and whole lung TL-FAPI (wlTL-FAPI).
  measure: Correlate biomarkers to pulmonary SUV values
  time frame: At time of inclusion (T0)
  description: A correlation between the pulmonary FAPI uptake, reported as SUV values (see outcome 1) will be correlated with fibrosis and inflammatory specific biomarkers using Pearson's or Spearman's test.
  measure: 6 minute walking test vs pulmonary SUV values
  time frame: At time of inclusion (T0)
  description: The total walked distance in meters during 6 minutes is correlated with pulmonary FAPI uptake, reported as SUV values (see outcome 1) using Pearson's or Spearman's test.
  measure: DCLO and VC vs pulmonary SUV values
  time frame: At time of inclusion (T0)
  description: Pulmonary FAPI uptake, reported as SUV values (see outcome 1), will be correlated with DCLO and VC using Pearon's or Spearman's test.
  measure: Daily impairments (EQ-5D questionnaire) vs pulmonary SUV values
  time frame: At time of inclusion (T0)
  description: Pulmonary FAPI uptake, reported as SUV values (see outcome 1), will be correlated with self-reported daily impairments per category as measured by the EQ-5D questionnaire using Pearson's or Spearman's test.
  measure: Cellular phenotypes
  time frame: At time of inclusion (T0)
  description: Pulmonary FAPI uptake, reported as SUV values (see outcome 1), will be correlated to systemic and upper respiratory tract cellular phenotypes determined by single cell RNA sequencing using Pearon's or Spearmen's test.
  measure: HRCT
  time frame: At time of inclusion (T0)
  description: Pulmonary FAPI uptake, reported as SUV values (see outcome 1), will be correlated to HRCT findings: extent of disease (0-100%), reticular pattern (0-100%), portion of groundglass (0-100%), coarness (0-3), honey combing (Yes/No), Distribution groundglass, crazy-paving pattern (Yes/No), fibrosis (Yes/No), Bronchiectasis (Yes/No), Emfyseem (Yes/No) and Pleural effusion (Yes/No).
  measure: Follow-up HRCT
  time frame: 10 months after T0
  description: Pulmonary FAPI uptake, reported as SUV values (see outcome 1), will be correlated to HRCT findings in case of persistent respiratory complaints 8-10 months after T0. Findings that are correlated are: extent of disease (0-100%), reticular pattern (0-100%), portion of groundglass (0-100%), coarness (0-3), honey combing (Yes/No), Distribution groundglass, crazy-paving pattern (Yes/No), fibrosis (Yes/No), Bronchiectasis (Yes/No), Emfyseem (Yes/No) and Pleural effusion (Yes/No).
  measure: Follow-up daily impairments (EQ-5D questionnaire) vs pulmonary SUV values
  time frame: 10 months after T0
  description: Pulmonary FAPI uptake, reported as SUV values (see outcome 1), will be correlated with self-reported daily impairments per category as measured by the EQ-5D questionnaire using Pearson's or Spearman's test.
  Blood and nose epithelium for single cell RNA analysis
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Riemer Slart, Prof MD PhD
  role: Principal Investigator
  affiliation: University Medical Center Groningen
  last name: Janesh Pillay, MD PhD
  phone: 0625650720
  phone ext: +31
  email: j.pillay@umcg.nl
  last name: Bram van Leer, MD
  email: b.van.leer@umcg.nl
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  investigator: 
  country: Netherlands
  responsible party type: Sponsor
  mesh term: COVID-19
  mesh term: Post-Acute COVID-19 Syndrome
  mesh term: Pulmonary Fibrosis
  sharing ipd: Yes
  ipd description: Data underlie the results reported in this article will be shared on reasonably request after deidentification of individual participant data. Only investigators whose proposed use of data is for individual participant data meta-analysis and in line with the signed informed consent are eligible for sharing. Proposals should be directed to r.h.j.a.slart@umcg.nl. To gain access, data requestors will need to sign a data access agreement.
  ipd info type: Study Protocol
  ipd time frame: Directly after publication
  ipd access criteria: Only investigators whose proposed use of data is for individual participant data meta-analysis and in line with the signed informed consent are eligible for sharing
  provided document: 