<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/NCT03285945</url>
  </required_header>
  <id_info>
    <org_study_id>akutPET</org_study_id>
    <nct_id>NCT03285945</nct_id>
  </id_info>
  <brief_title>FDG Uptake in Large-Vessel Giant Cell Arteritis After Short-term, High-Dose Steroid Treatment</brief_title>
  <official_title>Fluorine-18-fluorodeoxyglucose Uptake in Large-Vessel Giant Cell Arteritis After Short-term, High-Dose Steroid Treatment - A Diagnostic Window of Opportunity?</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Aarhus</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Aarhus</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Giant cell arteritis (GCA) affects large and medium sized vessels. Large vessel-GCA (LV-GCA)&#xD;
      affecting aorta and/or its main branches is seen a) together with temporal arteritis&#xD;
      (AT-GCA), b) as isolated LV-GCA but also c) with polymyalgia rheumatica.&#xD;
&#xD;
      There is a risk of vision loss and cerebral thromboembolic events or great vessel injury in&#xD;
      GCA. With delayed or inadequate treatment mortality and morbidity increases. This highlights&#xD;
      the need of fast diagnosis and early treatment.&#xD;
&#xD;
      The cornerstone in the diagnosis of GCA is a positive temporal artery biopsy. Patients with&#xD;
      LV-GCA have more general, but less cephalic symptoms than patients with AT-GCA. Also, biopsy&#xD;
      from large vessels can rarely be done and only 50% have a positive temporal artery biopsy&#xD;
      (TAB). Hence, diagnosis often rely on imaging.&#xD;
&#xD;
      Fluorine-18-fluorodeoxyglucose positron-emission tomography (FDG PET)/CT has shown high&#xD;
      diagnostic sensitivity and specificity and is believed to be superior to other imaging&#xD;
      modalities in the diagnosis of LV-GCA . The impact of FDG PET/CT in the management of LV-GCA&#xD;
      has been evaluated and has shown to increase the diagnostic accuracy in a significant&#xD;
      proportion of patients. However, studies have indicated a lower sensitivity in steroid&#xD;
      treated patients.&#xD;
&#xD;
      The aim of this study, was to evaluate the effect of steroid treatment on large-vessel FDG&#xD;
      uptake in new-onset, treatment-naive LV-GCA by repetitive FDG PET/CT pre- and post&#xD;
      therapeutic. With insights into the diagnostic capabilities after treatment is initiated, the&#xD;
      possibility of timely treatment and confident diagnostic work up will improve.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      As standard of care, patients suspected of GCA undergo clinical examination, laboratory&#xD;
      screening, temporal artery biopsy, vascular ultrasound examination and FDG PET/CT.&#xD;
&#xD;
      All patients with a diagnosis of GCA will be treated with 60 mg af prednisolone and tapered&#xD;
      according to a predefined algorithm.&#xD;
&#xD;
      In patients with FDG PET/CT verified LV-GCA, FDG PET/CT is repeated after either 3 (n=12) or&#xD;
      10 (n=12) days of steroid treatment.&#xD;
&#xD;
      An experienced nuclear medicine physician (LCG), blinded to clinical symptoms and findings,&#xD;
      qualitatively assesses PET scans. A semiquantitative approach is applied (a.m. Meller) in&#xD;
      which FDG uptake in vascular regions is graded on a 5-point scale (0 = no uptake, 1 = uptake&#xD;
      below or equal to blood pool, 2 = above blood pool but below liver, 3 = above liver, 4 = 2&#xD;
      times above liver). Any score ≥3 is considered consistent with vasculitis. Sensitivity of&#xD;
      post-therapeutic FDG PET/CT will be evaluated.&#xD;
&#xD;
      Moreover, standard uptake values (SUV) mean and maximum values in vascular regions will be&#xD;
      calculated. A ratio SUV(wall)/SUV(blood pool) and a total metabolic burden (TMB) based on&#xD;
      affected vascular volume and SUV mean values are obtained as measures of vascular wall&#xD;
      inflammation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">September 2016</completion_date>
  <primary_completion_date type="Actual">September 2016</primary_completion_date>
  <study_type>Observational</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>
  <primary_outcome>
    <measure>Proportion of large vessel-GCA patients with post-therapeutic FDG uptake consistent with a diagnosis of large vessel giant cell arteritis</measure>
    <time_frame>Assessed after intervention (3 or 10 days of treatment, respectively)</time_frame>
    <description>Proportion of patients with PET positive large vessel vasculitis defined as vascular FDG uptake≥3, semiquantitative assesment ad modum Meller</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in quantitive uptake values (SUV)</measure>
    <time_frame>From baseline to post-treatments scan (3 or 10 days of treatment, respectively)</time_frame>
    <description>The steroid induced change in FDG uptake assessed by; change in maximum standardized uptake values (SUV)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in quantitive uptake values (TBR)</measure>
    <time_frame>From baseline to post-treatments scan (3 or 10 days of treatment, respectively)</time_frame>
    <description>The steroid induced change in FDG uptake assessed by; change in target to background ratio (TBR)= SUVmax(artery)/SUVmean(venous blood pool)</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">24</enrollment>
  <condition>Giant Cell Arteritis</condition>
  <arm_group>
    <arm_group_label>PET3</arm_group_label>
    <description>Post-therapeutic FDG PET/CT performed after 3 days of steroid treatment</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PET10</arm_group_label>
    <description>Post-therapeutic FDG PET/CT performed after 10 days of steroid treatment</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PET3</intervention_name>
    <description>Prednisolone 60 mg daily for 3 days</description>
    <arm_group_label>PET3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PET10</intervention_name>
    <description>Prednisolone 60 mg daily for 10 days</description>
    <arm_group_label>PET10</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Temporal artery biopsies, whole blood, serum, plasma&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Steroid-naive, newly-diagnosed giant cell arteritis patients&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Clinical suspicion of GCA; Cranial symptoms, new-onset extremity claudication or&#xD;
             protracted constitutional symptoms (weight loss &gt; 5 kilograms or fever &gt;38C for &gt; 3&#xD;
             weeks).&#xD;
&#xD;
          2. C reactive protein &gt;15 mg/l or erythrocyte sedimentation rate &gt;40 mm/h&#xD;
&#xD;
          3. FDG PET/CT verified LV-GCA (steroid-naive) defined by FDG uptake in the aortic wall&#xD;
             and/or supra-aortic branches with FDG uptake score ≥3.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. oral glucocorticoid treatment within the past month&#xD;
&#xD;
          2. subcutaneously, intramuscularly, intraarticularly or intravenously administered&#xD;
             glucocorticoid within the past 2 months&#xD;
&#xD;
          3. treatment with DMARDs or other immunosuppressive therapy ongoing or within the past 3&#xD;
             months&#xD;
&#xD;
          4. ongoing treatment with interleukin2&#xD;
&#xD;
          5. any disease mimicking GCA, including&#xD;
&#xD;
               -  a) autoimmune diseases with possible aortitis; rheumatoid arthritis, Cogans&#xD;
                  syndrome, relapsing polychondritis, ankylosing spondylitis, systemic lupus&#xD;
                  erythematosus, Buerger's disease, Bechet's disease, inflammatory bowel disease&#xD;
&#xD;
               -  b) infections with possible aortitis: syphilis, known active current or history&#xD;
                  of recurrent tuberculosis, hepatitis or HIV&#xD;
&#xD;
               -  c) other large-vessel disease: sarcoidosis, neurofibromatosis, congenital&#xD;
                  coarctation, Marfans syndrome, Ehlers-Danlos syndrome, retroperitoneal fibrosis&#xD;
&#xD;
          6. body weight of &gt;150 kg.&#xD;
&#xD;
          7. Previously diagnosed and treated for PMR or GCA&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ellen-Margrethe Hauge, Prof MD PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Department of Rheumatology , Aarhus University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Rheumatology</name>
      <address>
        <city>Aarhus</city>
        <zip>8000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <reference>
    <citation>Puppo C, Massollo M, Paparo F, Camellino D, Piccardo A, Shoushtari Zadeh Naseri M, Villavecchia G, Rollandi GA, Cimmino MA. Giant cell arteritis: a systematic review of the qualitative and semiquantitative methods to assess vasculitis with 18F-fluorodeoxyglucose positron emission tomography. Biomed Res Int. 2014;2014:574248. doi: 10.1155/2014/574248. Epub 2014 Sep 1.</citation>
    <PMID>25254211</PMID>
  </reference>
  <reference>
    <citation>Stellingwerff MD, Brouwer E, Lensen KDF, Rutgers A, Arends S, van der Geest KSM, Glaudemans AWJM, Slart RHJA. Different Scoring Methods of FDG PET/CT in Giant Cell Arteritis: Need for Standardization. Medicine (Baltimore). 2015 Sep;94(37):e1542. doi: 10.1097/MD.0000000000001542.</citation>
    <PMID>26376404</PMID>
  </reference>
  <reference>
    <citation>Fuchs M, Briel M, Daikeler T, Walker UA, Rasch H, Berg S, Ng QK, Raatz H, Jayne D, Kotter I, Blockmans D, Cid MC, Prieto-Gonzalez S, Lamprecht P, Salvarani C, Karageorgaki Z, Watts R, Luqmani R, Muller-Brand J, Tyndall A, Walter MA. The impact of 18F-FDG PET on the management of patients with suspected large vessel vasculitis. Eur J Nucl Med Mol Imaging. 2012 Feb;39(2):344-53. doi: 10.1007/s00259-011-1967-x. Epub 2011 Nov 10.</citation>
    <PMID>22072285</PMID>
  </reference>
  <reference>
    <citation>Prieto-Gonzalez S, Depetris M, Garcia-Martinez A, Espigol-Frigole G, Tavera-Bahillo I, Corbera-Bellata M, Planas-Rigol E, Alba MA, Hernandez-Rodriguez J, Grau JM, Lomena F, Cid MC. Positron emission tomography assessment of large vessel inflammation in patients with newly diagnosed, biopsy-proven giant cell arteritis: a prospective, case-control study. Ann Rheum Dis. 2014 Jul;73(7):1388-92. doi: 10.1136/annrheumdis-2013-204572. Epub 2014 Mar 24.</citation>
    <PMID>24665112</PMID>
  </reference>
  <verification_date>October 2016</verification_date>
  <study_first_submitted>October 12, 2016</study_first_submitted>
  <study_first_submitted_qc>September 15, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 18, 2017</study_first_posted>
  <last_update_submitted>September 15, 2017</last_update_submitted>
  <last_update_submitted_qc>September 15, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 18, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Positron-Emission Tomography</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Polymyalgia Rheumatica</mesh_term>
    <mesh_term>Giant Cell Arteritis</mesh_term>
    <mesh_term>Arteritis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03285945
org study id: akutPET
nct id: NCT03285945
lead sponsor: 
has dmc: No
Giant cell arteritis (GCA) affects large and medium sized vessels. Large vessel-GCA (LV-GCA)
      affecting aorta and/or its main branches is seen a) together with temporal arteritis
      (AT-GCA), b) as isolated LV-GCA but also c) with polymyalgia rheumatica.

      There is a risk of vision loss and cerebral thromboembolic events or great vessel injury in
      GCA. With delayed or inadequate treatment mortality and morbidity increases. This highlights
      the need of fast diagnosis and early treatment.

      The cornerstone in the diagnosis of GCA is a positive temporal artery biopsy. Patients with
      LV-GCA have more general, but less cephalic symptoms than patients with AT-GCA. Also, biopsy
      from large vessels can rarely be done and only 50% have a positive temporal artery biopsy
      (TAB). Hence, diagnosis often rely on imaging.

      Fluorine-18-fluorodeoxyglucose positron-emission tomography (FDG PET)/CT has shown high
      diagnostic sensitivity and specificity and is believed to be superior to other imaging
      modalities in the diagnosis of LV-GCA . The impact of FDG PET/CT in the management of LV-GCA
      has been evaluated and has shown to increase the diagnostic accuracy in a significant
      proportion of patients. However, studies have indicated a lower sensitivity in steroid
      treated patients.

      The aim of this study, was to evaluate the effect of steroid treatment on large-vessel FDG
      uptake in new-onset, treatment-naive LV-GCA by repetitive FDG PET/CT pre- and post
      therapeutic. With insights into the diagnostic capabilities after treatment is initiated, the
      possibility of timely treatment and confident diagnostic work up will improve.
As standard of care, patients suspected of GCA undergo clinical examination, laboratory
      screening, temporal artery biopsy, vascular ultrasound examination and FDG PET/CT.

      All patients with a diagnosis of GCA will be treated with 60 mg af prednisolone and tapered
      according to a predefined algorithm.

      In patients with FDG PET/CT verified LV-GCA, FDG PET/CT is repeated after either 3 (n=12) or
      10 (n=12) days of steroid treatment.

      An experienced nuclear medicine physician (LCG), blinded to clinical symptoms and findings,
      qualitatively assesses PET scans. A semiquantitative approach is applied (a.m. Meller) in
      which FDG uptake in vascular regions is graded on a 5-point scale (0 = no uptake, 1 = uptake
      below or equal to blood pool, 2 = above blood pool but below liver, 3 = above liver, 4 = 2
      times above liver). Any score ≥3 is considered consistent with vasculitis. Sensitivity of
      post-therapeutic FDG PET/CT will be evaluated.

      Moreover, standard uptake values (SUV) mean and maximum values in vascular regions will be
      calculated. A ratio SUV(wall)/SUV(blood pool) and a total metabolic burden (TMB) based on
      affected vascular volume and SUV mean values are obtained as measures of vascular wall
      inflammation.
observational model: Cohort
time perspective: Prospective
measure: Proportion of large vessel-GCA patients with post-therapeutic FDG uptake consistent with a diagnosis of large vessel giant cell arteritis
time frame: Assessed after intervention (3 or 10 days of treatment, respectively)
description: Proportion of patients with PET positive large vessel vasculitis defined as vascular FDG uptake≥3, semiquantitative assesment ad modum Meller
measure: Change in quantitive uptake values (SUV)
time frame: From baseline to post-treatments scan (3 or 10 days of treatment, respectively)
description: The steroid induced change in FDG uptake assessed by; change in maximum standardized uptake values (SUV)
measure: Change in quantitive uptake values (TBR)
time frame: From baseline to post-treatments scan (3 or 10 days of treatment, respectively)
description: The steroid induced change in FDG uptake assessed by; change in target to background ratio (TBR)= SUVmax(artery)/SUVmean(venous blood pool)
arm group label: PET3
description: Post-therapeutic FDG PET/CT performed after 3 days of steroid treatment
arm group label: PET10
description: Post-therapeutic FDG PET/CT performed after 10 days of steroid treatment
intervention type: Drug
intervention name: PET3
description: Prednisolone 60 mg daily for 3 days
arm group label: PET3
intervention type: Drug
intervention name: PET10
description: Prednisolone 60 mg daily for 10 days
arm group label: PET10
Temporal artery biopsies, whole blood, serum, plasma
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: No
last name: Ellen-Margrethe Hauge, Prof MD PhD
role: Study Chair
affiliation: Department of Rheumatology , Aarhus University Hospital
facility: 
country: Denmark
citation: Puppo C, Massollo M, Paparo F, Camellino D, Piccardo A, Shoushtari Zadeh Naseri M, Villavecchia G, Rollandi GA, Cimmino MA. Giant cell arteritis: a systematic review of the qualitative and semiquantitative methods to assess vasculitis with 18F-fluorodeoxyglucose positron emission tomography. Biomed Res Int. 2014;2014:574248. doi: 10.1155/2014/574248. Epub 2014 Sep 1.
PMID: 25254211
citation: Stellingwerff MD, Brouwer E, Lensen KDF, Rutgers A, Arends S, van der Geest KSM, Glaudemans AWJM, Slart RHJA. Different Scoring Methods of FDG PET/CT in Giant Cell Arteritis: Need for Standardization. Medicine (Baltimore). 2015 Sep;94(37):e1542. doi: 10.1097/MD.0000000000001542.
PMID: 26376404
citation: Fuchs M, Briel M, Daikeler T, Walker UA, Rasch H, Berg S, Ng QK, Raatz H, Jayne D, Kotter I, Blockmans D, Cid MC, Prieto-Gonzalez S, Lamprecht P, Salvarani C, Karageorgaki Z, Watts R, Luqmani R, Muller-Brand J, Tyndall A, Walter MA. The impact of 18F-FDG PET on the management of patients with suspected large vessel vasculitis. Eur J Nucl Med Mol Imaging. 2012 Feb;39(2):344-53. doi: 10.1007/s00259-011-1967-x. Epub 2011 Nov 10.
PMID: 22072285
citation: Prieto-Gonzalez S, Depetris M, Garcia-Martinez A, Espigol-Frigole G, Tavera-Bahillo I, Corbera-Bellata M, Planas-Rigol E, Alba MA, Hernandez-Rodriguez J, Grau JM, Lomena F, Cid MC. Positron emission tomography assessment of large vessel inflammation in patients with newly diagnosed, biopsy-proven giant cell arteritis: a prospective, case-control study. Ann Rheum Dis. 2014 Jul;73(7):1388-92. doi: 10.1136/annrheumdis-2013-204572. Epub 2014 Mar 24.
PMID: 24665112
responsible party type: Sponsor
mesh term: Polymyalgia Rheumatica
mesh term: Giant Cell Arteritis
mesh term: Arteritis
sharing ipd: Undecided