<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/NCT03248284</url>
  </required_header>
  <id_info>
    <org_study_id>OUH-IMPAACT-02</org_study_id>
    <nct_id>NCT03248284</nct_id>
  </id_info>
  <brief_title>Immune-Competent Cell Manifestations in Psoriatic Arthritis Achilles Tendons</brief_title>
  <acronym>IMPAACT</acronym>
  <official_title>Stereological Quantification of Immune-Competent Cells in Biopsies From Painful Achilles Tendons of Psoriatic Arthritis Patients With Ultrasonic Verified Enthesitis: An Exploratory Prospective Cohort Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Odense University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Southern Denmark</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Odense Patient Data Explorative Network</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Danish Rheumatism Association</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Psoriasis Association, Denmark</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Odense University Hospital</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>
      Tendon pathologies (enthesitis) are a characteristic component of psoriatic arthritis (PsA),&#xD;
      and are observed in 35% to 50% of PsA patients. The Achilles tendon is one of the most&#xD;
      commonly affected sites. This condition often causes great morbidity and loss of quality of&#xD;
      life, and response only suboptimal to current intervention strategies. One of the main&#xD;
      obstacles for the development of effective treatment methods is that the disease mechanisms&#xD;
      remain poorly understood. To our knowledge, no one has yet ascertained the presence and&#xD;
      function of immune-competent cells and inflammatory markers in tendons tissue from PsA&#xD;
      patients suffering from Achilles enthesitis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Aim: The main objective of the IMPAACT study is to describe the histological findings of PsA&#xD;
      Achilles enthesitis, and to a) Characterize and b) Quantify the immune-competent cell&#xD;
      presence in tendon specimens obtained from the mid-portion and entheseal site of the Achilles&#xD;
      tendon from PsA patients with enthesitis using immunohistochemistry and a stereological&#xD;
      technique for the quantification. And secondly, to compare these observations with a) Those&#xD;
      in healthy Achilles tendons, and b) Those in mono-symptomatic, non-PsA, chronic Achilles&#xD;
      tendinopathy. Secondly, to examine whether one or more of the immune-competent cell types in&#xD;
      the PsA tendons are associated with 3-months remission rate of Achilles tendon pain, or with&#xD;
      baseline a) Ultrasonic findings of the Achilles tendon; b) PsA disease activity; c) Tendon&#xD;
      protein analyses; d) Risk factors of cardiovascular disease; e) Blood biomarkers of systemic&#xD;
      inflammation; and f) Fecal microbiota composition.&#xD;
&#xD;
      Methods: This study (IMPAACT) is a prospective, cohort study including 30 PsA patients&#xD;
      (fulfilling the the Classification Criteria for Psoriatic Arthritis (CASPAR criteria)) with&#xD;
      pain at the Achilles tendon insertion. At baseline, all participants will be examined&#xD;
      clinically regarding overall PsA disease activity (Psoriasis Area Severity Index (PASI skin&#xD;
      score), the Research Consortium of Canada (SPARCC) Enthesitis score, swollen/tender joint&#xD;
      count) and asked to fill out a questionnaire consisting of the validated Scandinavian&#xD;
      (Danish) version of the Victorian Institute of Sport Assessment of Achilles tendons (VISA-A)&#xD;
      in addition to a study-composed questionnaire comprising general questions regarding patient&#xD;
      characteristics. An ultrasonic examination of the Achilles tendons will be performed before&#xD;
      ultrasound guided Achilles tendon specimens will be obtained from the most painful Achilles&#xD;
      tendon. Tendon samples will be evaluated immunohistochemically by quantifying the presence of&#xD;
      macrophages (CD68-KP1+), T-lymphocytes (CD3+), B-lymphocytes (CD20+), natural killer cells&#xD;
      (CD56+), neutrophils (granzyme-B+), mast cells and inflammatory markers using a stereological&#xD;
      technique. Also, a protein analysis of the tendon tissue will be conducted. Venous blood will&#xD;
      be analysed for levels of systemic inflammatory markers, as well as screened for&#xD;
      cardiovascular risk factors including dyslipidaemia, and diabetes. After the baseline&#xD;
      examination, all participants will be treated and monitored in accordance with the Danish&#xD;
      national guideline recommendations for PsA patients. A 3-months follow-up examination will be&#xD;
      performed to determine the remission status of the Achilles tendon pain. Data will be&#xD;
      analysed using the STATA statistical package (version 12; StataCorp LP).&#xD;
&#xD;
      Conclusion: PsA is a painful and debilitating inflammatory disease. The current treatment&#xD;
      remains suboptimal. We hope to provide new insight into the cellular mechanisms underlying&#xD;
      PsA tendon and enthesis pathologies.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">August 21, 2017</start_date>
  <completion_date type="Anticipated">October 1, 2022</completion_date>
  <primary_completion_date type="Anticipated">July 1, 2022</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>Presence of Immune-competent cells and inflammatory markers</measure>
    <time_frame>Baseline</time_frame>
    <description>CD3, CD4, CD8, CD20, CD34 (or CD31), CD56, S100 beta (CD57), CD68 (PGM1) or CD163, TNF-alfa, IL-6, IL-23 and other inflammatory markers.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Protein analyses</measure>
    <time_frame>Baseline</time_frame>
    <description>Protein analyses performed on Achilles tendon tissue</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>From baseline to 3-month follow-up</time_frame>
    <description>Number of adverse events during follow-up</description>
  </secondary_outcome>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Psoriatic Arthritis</condition>
  <condition>Enthesitis</condition>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Tendon biopsy procedure</intervention_name>
    <description>Two tendon biopsy specimens will be obtained from one Achilles tendon with enthesitis.</description>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Achilles tendon tissue specimens, blood- and fecal samples&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Psoriatic arthritis patients with Achilles enthesitis.&#xD;
&#xD;
        There will be no restrictions regarding previous or current local and/or systemic&#xD;
        anti-inflammatory treatments, however, any type of such treatment will be registered and&#xD;
        used to stratify patients into treatment groups for the statistical analysis. Patients who&#xD;
        have never received any systemic and/or local anti-inflammatory treatment will be referred&#xD;
        to as treatment naïve.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Fulfilling the CASPAR criteria&#xD;
&#xD;
          -  Insertional Achilles tendon pain&#xD;
&#xD;
          -  Ultrasonic findings of inflammatory disease at the painful Achilles tendon insertion&#xD;
             (= enthesitis) defined as abnormally hypoechoic (loss of normal fibrillar&#xD;
             architecture) and/or thickened tendon at its bony attachment, seen in two&#xD;
             perpendicular planes that may exhibit a Doppler signal or bony changes, including&#xD;
             enthesophytes, and erosions.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Other inflammatory rheumatic diseases than PsA&#xD;
&#xD;
          -  Ultrasonic signs of complete rupture of the Achilles tendon&#xD;
&#xD;
          -  Not wishing to participate or not suited for project evaluation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
  </eligibility>
  <overall_official>
    <last_name>Maja S Kragsnaes, MD PhDfellow</last_name>
    <role>Principal Investigator</role>
    <affiliation>Odense University Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Maja S. Kragsnaes, MD PhDfellow</last_name>
    <phone>+ 45 23238663</phone>
    <email>maja.kragsnaes@dadlnet.dk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Torkell J. Ellingsen, Prof MD PhD</last_name>
    <email>torkell.ellingsen@rsyd.dk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Odense University Hospital</name>
      <address>
        <city>Odense</city>
        <zip>5000</zip>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Torkell J. Ellingsen, Prof MD PhD</last_name>
      <phone>+45 23238663</phone>
      <email>torkell.ellingsen@rsyd.dk</email>
    </contact>
    <contact_backup>
      <last_name>Maja S. Kragsnaes, MD PhDfellow</last_name>
      <email>maja.kragsnaes@dadlnet.dk</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Diagnostic Center</name>
      <address>
        <city>Silkeborg</city>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Maja S. Kragsnaes</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <reference>
    <citation>McGonagle DG, Helliwell P, Veale D. Enthesitis in psoriatic disease. Dermatology. 2012;225(2):100-9. doi: 10.1159/000341536. Epub 2012 Oct 27.</citation>
    <PMID>23108016</PMID>
  </reference>
  <reference>
    <citation>Terslev L, Naredo E, Iagnocco A, Balint PV, Wakefield RJ, Aegerter P, Aydin SZ, Bachta A, Hammer HB, Bruyn GA, Filippucci E, Gandjbakhch F, Mandl P, Pineda C, Schmidt WA, D'Agostino MA; Outcome Measures in Rheumatology Ultrasound Task Force. Defining enthesitis in spondyloarthritis by ultrasound: results of a Delphi process and of a reliability reading exercise. Arthritis Care Res (Hoboken). 2014 May;66(5):741-8. doi: 10.1002/acr.22191. Erratum In: Arthritis Care Res (Hoboken). 2017 Feb;69(2):311.</citation>
    <PMID>24151222</PMID>
  </reference>
  <reference>
    <citation>Khan KM, Cook JL, Bonar F, Harcourt P, Astrom M. Histopathology of common tendinopathies. Update and implications for clinical management. Sports Med. 1999 Jun;27(6):393-408. doi: 10.2165/00007256-199927060-00004.</citation>
    <PMID>10418074</PMID>
  </reference>
  <reference>
    <citation>Fredberg U, Stengaard-Pedersen K. Chronic tendinopathy tissue pathology, pain mechanisms, and etiology with a special focus on inflammation. Scand J Med Sci Sports. 2008 Feb;18(1):3-15. doi: 10.1111/j.1600-0838.2007.00746.x.</citation>
    <PMID>18294189</PMID>
  </reference>
  <reference>
    <citation>Ryan C, Korman NJ, Gelfand JM, Lim HW, Elmets CA, Feldman SR, Gottlieb AB, Koo JY, Lebwohl M, Leonardi CL, Van Voorhees AS, Bhushan R, Menter A. Research gaps in psoriasis: opportunities for future studies. J Am Acad Dermatol. 2014 Jan;70(1):146-67. doi: 10.1016/j.jaad.2013.08.042. Epub 2013 Oct 11.</citation>
    <PMID>24126079</PMID>
  </reference>
  <reference>
    <citation>Jacques P, Lambrecht S, Verheugen E, Pauwels E, Kollias G, Armaka M, Verhoye M, Van der Linden A, Achten R, Lories RJ, Elewaut D. Proof of concept: enthesitis and new bone formation in spondyloarthritis are driven by mechanical strain and stromal cells. Ann Rheum Dis. 2014 Feb;73(2):437-45. doi: 10.1136/annrheumdis-2013-203643. Epub 2013 Aug 6.</citation>
    <PMID>23921997</PMID>
  </reference>
  <reference>
    <citation>Kragsnaes MS, Fredberg U, Stribolt K, Kjaer SG, Bendix K, Ellingsen T. Stereological quantification of immune-competent cells in baseline biopsy specimens from achilles tendons: results from patients with chronic tendinopathy followed for more than 4 years. Am J Sports Med. 2014 Oct;42(10):2435-45. doi: 10.1177/0363546514542329. Epub 2014 Jul 31.</citation>
    <PMID>25081311</PMID>
  </reference>
  <reference>
    <citation>McGonagle D, Marzo-Ortega H, O'Connor P, Gibbon W, Hawkey P, Henshaw K, Emery P. Histological assessment of the early enthesitis lesion in spondyloarthropathy. Ann Rheum Dis. 2002 Jun;61(6):534-7. doi: 10.1136/ard.61.6.534.</citation>
    <PMID>12006328</PMID>
  </reference>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>August 9, 2017</study_first_submitted>
  <study_first_submitted_qc>August 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 14, 2017</study_first_posted>
  <last_update_submitted>June 7, 2021</last_update_submitted>
  <last_update_submitted_qc>June 7, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 8, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Odense University Hospital</investigator_affiliation>
    <investigator_full_name>Torkell Ellingsen</investigator_full_name>
    <investigator_title>Prof MD PhD</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Arthritis</mesh_term>
    <mesh_term>Arthritis, Psoriatic</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/NCT03248284
org study id: OUH-IMPAACT-02
nct id: NCT03248284
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Tendon pathologies (enthesitis) are a characteristic component of psoriatic arthritis (PsA),
      and are observed in 35% to 50% of PsA patients. The Achilles tendon is one of the most
      commonly affected sites. This condition often causes great morbidity and loss of quality of
      life, and response only suboptimal to current intervention strategies. One of the main
      obstacles for the development of effective treatment methods is that the disease mechanisms
      remain poorly understood. To our knowledge, no one has yet ascertained the presence and
      function of immune-competent cells and inflammatory markers in tendons tissue from PsA
      patients suffering from Achilles enthesitis.
Aim: The main objective of the IMPAACT study is to describe the histological findings of PsA
      Achilles enthesitis, and to a) Characterize and b) Quantify the immune-competent cell
      presence in tendon specimens obtained from the mid-portion and entheseal site of the Achilles
      tendon from PsA patients with enthesitis using immunohistochemistry and a stereological
      technique for the quantification. And secondly, to compare these observations with a) Those
      in healthy Achilles tendons, and b) Those in mono-symptomatic, non-PsA, chronic Achilles
      tendinopathy. Secondly, to examine whether one or more of the immune-competent cell types in
      the PsA tendons are associated with 3-months remission rate of Achilles tendon pain, or with
      baseline a) Ultrasonic findings of the Achilles tendon; b) PsA disease activity; c) Tendon
      protein analyses; d) Risk factors of cardiovascular disease; e) Blood biomarkers of systemic
      inflammation; and f) Fecal microbiota composition.

      Methods: This study (IMPAACT) is a prospective, cohort study including 30 PsA patients
      (fulfilling the the Classification Criteria for Psoriatic Arthritis (CASPAR criteria)) with
      pain at the Achilles tendon insertion. At baseline, all participants will be examined
      clinically regarding overall PsA disease activity (Psoriasis Area Severity Index (PASI skin
      score), the Research Consortium of Canada (SPARCC) Enthesitis score, swollen/tender joint
      count) and asked to fill out a questionnaire consisting of the validated Scandinavian
      (Danish) version of the Victorian Institute of Sport Assessment of Achilles tendons (VISA-A)
      in addition to a study-composed questionnaire comprising general questions regarding patient
      characteristics. An ultrasonic examination of the Achilles tendons will be performed before
      ultrasound guided Achilles tendon specimens will be obtained from the most painful Achilles
      tendon. Tendon samples will be evaluated immunohistochemically by quantifying the presence of
      macrophages (CD68-KP1+), T-lymphocytes (CD3+), B-lymphocytes (CD20+), natural killer cells
      (CD56+), neutrophils (granzyme-B+), mast cells and inflammatory markers using a stereological
      technique. Also, a protein analysis of the tendon tissue will be conducted. Venous blood will
      be analysed for levels of systemic inflammatory markers, as well as screened for
      cardiovascular risk factors including dyslipidaemia, and diabetes. After the baseline
      examination, all participants will be treated and monitored in accordance with the Danish
      national guideline recommendations for PsA patients. A 3-months follow-up examination will be
      performed to determine the remission status of the Achilles tendon pain. Data will be
      analysed using the STATA statistical package (version 12; StataCorp LP).

      Conclusion: PsA is a painful and debilitating inflammatory disease. The current treatment
      remains suboptimal. We hope to provide new insight into the cellular mechanisms underlying
      PsA tendon and enthesis pathologies.
observational model: Cohort
time perspective: Prospective
measure: Presence of Immune-competent cells and inflammatory markers
time frame: Baseline
description: CD3, CD4, CD8, CD20, CD34 (or CD31), CD56, S100 beta (CD57), CD68 (PGM1) or CD163, TNF-alfa, IL-6, IL-23 and other inflammatory markers.
measure: Protein analyses
time frame: Baseline
description: Protein analyses performed on Achilles tendon tissue
measure: Adverse events
time frame: From baseline to 3-month follow-up
description: Number of adverse events during follow-up
intervention type: Procedure
intervention name: Tendon biopsy procedure
description: Two tendon biopsy specimens will be obtained from one Achilles tendon with enthesitis.
Achilles tendon tissue specimens, blood- and fecal samples
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
last name: Maja S Kragsnaes, MD PhDfellow
role: Principal Investigator
affiliation: Odense University Hospital
last name: Maja S. Kragsnaes, MD PhDfellow
phone: + 45 23238663
email: maja.kragsnaes@dadlnet.dk
last name: Torkell J. Ellingsen, Prof MD PhD
email: torkell.ellingsen@rsyd.dk
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
country: Denmark
citation: McGonagle DG, Helliwell P, Veale D. Enthesitis in psoriatic disease. Dermatology. 2012;225(2):100-9. doi: 10.1159/000341536. Epub 2012 Oct 27.
PMID: 23108016
citation: Terslev L, Naredo E, Iagnocco A, Balint PV, Wakefield RJ, Aegerter P, Aydin SZ, Bachta A, Hammer HB, Bruyn GA, Filippucci E, Gandjbakhch F, Mandl P, Pineda C, Schmidt WA, D'Agostino MA; Outcome Measures in Rheumatology Ultrasound Task Force. Defining enthesitis in spondyloarthritis by ultrasound: results of a Delphi process and of a reliability reading exercise. Arthritis Care Res (Hoboken). 2014 May;66(5):741-8. doi: 10.1002/acr.22191. Erratum In: Arthritis Care Res (Hoboken). 2017 Feb;69(2):311.
PMID: 24151222
citation: Khan KM, Cook JL, Bonar F, Harcourt P, Astrom M. Histopathology of common tendinopathies. Update and implications for clinical management. Sports Med. 1999 Jun;27(6):393-408. doi: 10.2165/00007256-199927060-00004.
PMID: 10418074
citation: Fredberg U, Stengaard-Pedersen K. Chronic tendinopathy tissue pathology, pain mechanisms, and etiology with a special focus on inflammation. Scand J Med Sci Sports. 2008 Feb;18(1):3-15. doi: 10.1111/j.1600-0838.2007.00746.x.
PMID: 18294189
citation: Ryan C, Korman NJ, Gelfand JM, Lim HW, Elmets CA, Feldman SR, Gottlieb AB, Koo JY, Lebwohl M, Leonardi CL, Van Voorhees AS, Bhushan R, Menter A. Research gaps in psoriasis: opportunities for future studies. J Am Acad Dermatol. 2014 Jan;70(1):146-67. doi: 10.1016/j.jaad.2013.08.042. Epub 2013 Oct 11.
PMID: 24126079
citation: Jacques P, Lambrecht S, Verheugen E, Pauwels E, Kollias G, Armaka M, Verhoye M, Van der Linden A, Achten R, Lories RJ, Elewaut D. Proof of concept: enthesitis and new bone formation in spondyloarthritis are driven by mechanical strain and stromal cells. Ann Rheum Dis. 2014 Feb;73(2):437-45. doi: 10.1136/annrheumdis-2013-203643. Epub 2013 Aug 6.
PMID: 23921997
citation: Kragsnaes MS, Fredberg U, Stribolt K, Kjaer SG, Bendix K, Ellingsen T. Stereological quantification of immune-competent cells in baseline biopsy specimens from achilles tendons: results from patients with chronic tendinopathy followed for more than 4 years. Am J Sports Med. 2014 Oct;42(10):2435-45. doi: 10.1177/0363546514542329. Epub 2014 Jul 31.
PMID: 25081311
citation: McGonagle D, Marzo-Ortega H, O'Connor P, Gibbon W, Hawkey P, Henshaw K, Emery P. Histological assessment of the early enthesitis lesion in spondyloarthropathy. Ann Rheum Dis. 2002 Jun;61(6):534-7. doi: 10.1136/ard.61.6.534.
PMID: 12006328
responsible party type: Principal Investigator
investigator affiliation: Odense University Hospital
investigator full name: Torkell Ellingsen
investigator title: Prof MD PhD
mesh term: Arthritis
mesh term: Arthritis, Psoriatic
sharing ipd: No