<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/NCT03803462</url>
  </required_header>
  <id_info>
    <org_study_id>BODI</org_study_id>
    <nct_id>NCT03803462</nct_id>
  </id_info>
  <brief_title>Behçet's Disease Overall Damage Index</brief_title>
  <acronym>BODI</acronym>
  <official_title>Development and Preliminary Validation of the Behçet's Disease Overall Damage Index</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Cagliari</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Cagliari</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>
      Damage in vasculitis, as well as in other chronic inflammatory disorders, accrues over time&#xD;
      resulting in impairment of quality of life, development of disability and increased&#xD;
      mortality. For these reasons, damage represents an important outcome to be assessed and&#xD;
      measured both in trials and clinical practice.&#xD;
&#xD;
      Currently, the most widely used assessment tool for damage in vasculitis is the Vasculitis&#xD;
      Damage Index (VDI). However, VDI was developed for a no specific type of vasculitis and it&#xD;
      appears to be more suitable for damage assessment in ANCA-associated vasculitis than in&#xD;
      Behçet' disease (BD).&#xD;
&#xD;
      BD is a chronic and multisystem inflammatory disorder classified among vasculitides. As well&#xD;
      as in other vasculitides, disease activity and treatment in BD can result in the development&#xD;
      and accumulation of irreversible organ damage, such as blindness, tissue loss and a wide&#xD;
      range of neurologic disorders. Recently the OMERACT has defined the Core Set domain of&#xD;
      Outcome Measures for BD. Despite damage is included in the OMERACT outcome core set for&#xD;
      rheumatic disease, a specific assessment tool for BD is currently not available.&#xD;
&#xD;
      The aim of this study is to develop and validate the first tool for describing and measuring&#xD;
      organ damage in patients with Behçet Disease (Behçet's disease Overall Damage index - BODI).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      DESIGN OF THE STUDY&#xD;
&#xD;
      This observational multicenter study will be developed in 2 subsequent phases, in their turn,&#xD;
      consisting of different steps (figure 1):&#xD;
&#xD;
        1. BODI Development 1.1) Development of a preliminary version of BODI (p-BODI) based on&#xD;
           literature review and inspired by pre-existing tools according to OMERACT guidelines;&#xD;
           1.2) Delphi process aimed to review and improve the p-BODI.&#xD;
&#xD;
        2. Validation of the new tool according to OMERACT filter 2.0 2.1) Application of the BODI&#xD;
           on a multicentre cohort of BD patients. 2.2) Assessment of face, content, construct and&#xD;
           criterion validity, and sensitivity to change.&#xD;
&#xD;
      2.3) Assessment of reliability based on scoring exercise on clinical vignettes.&#xD;
&#xD;
      All subjects involved in the study are experts in the management of BD. They will work in two&#xD;
      different groups having different roles:&#xD;
&#xD;
        -  Work and facilitator group (WFG): consisting of 3 Physician from the Coordinating&#xD;
           Centre. The tasks of the WFG are: (a) to review literature and develop a preliminary&#xD;
           version of BODI (p-BODI), including: definition of damage, rules for scoring and&#xD;
           identification of potential items of damage; (b) to coordinate the Delphi process for&#xD;
           editing and optimizing p-BODI; (c) to analyse data from the validation process.&#xD;
&#xD;
        -  Expert Panel (EP): consisting of multidisciplinary experts in Behçet's disease and&#xD;
           Patient's delegate from different countries. EP members will be selected and invited to&#xD;
           participate in the study by the WFG. The tasks of the EP are to express their opinion on&#xD;
           p-BODI and propose editing for its improvement within a Delphi process;&#xD;
&#xD;
        -  Clinicians group (CG): consisting of one Clinician from each Centre, with expertise in&#xD;
           Behçet's disease but not involved in the Delphi process. The tasks of this group are:&#xD;
           (a) to apply the BODI on 30 consecutive patients with BD (10 for Neurologist and&#xD;
           Ophthalmologist) from each Centre involved in the study; (b) to score a set of clinical&#xD;
           vignettes using the BODI, to assess reliability of the instrument; (c) to express an&#xD;
           overall judgement (in an online survey) regarding to general credibility,&#xD;
           comprehensiveness and feasibility of the BODI.&#xD;
&#xD;
      The member of EP and GC, involved in the study so far, with respective affiliations, are&#xD;
      reported below:&#xD;
&#xD;
      EP members - CG members - Affiliations.&#xD;
&#xD;
        -  Prof. Alessandro Mathieu - Dr. Matteo Piga - Chair and Unit of Rheumatology, University&#xD;
           and AOU of Cagliari, Monserrato - Italy;&#xD;
&#xD;
        -  Prof. Govoni Marcello - Dr. Lo Monaco Andrea - Department of Medical Sciences, Section&#xD;
           of Rheumatology, AOU S. Anna, the University of Ferrara - Italy;&#xD;
&#xD;
        -  Prof. Iannone Florenzo - Dr. Lopalco Giuseppe - Department of Emergency and Organ&#xD;
           Transplantation, Rheumatology Unit, University of Bari - Italy;&#xD;
&#xD;
        -  Prof. Neri Piergiorgio - Dr. Pirani Vittorio - Ocular Immunology Service, the Eye&#xD;
           Clinic, Polytechnic University of Marche- Ancona - Italy;&#xD;
&#xD;
        -  Prof. Cantarini Luca - Dr. Orlando Ida - Rheumatology Unit, University of Siena.&#xD;
           Policlinico Le Scotte;&#xD;
&#xD;
        -  Prof. Martins Silva Ana - Dr. Santos Ernestina - Neurology Department, Hospital Santo&#xD;
           António, Centro Hospitalar do Porto - Portugal;&#xD;
&#xD;
        -  Prof. Vasconcelos Carlos - Prof Correia Joao; Dr. Raquel Faria - Clinical Immunology&#xD;
           Unit, Centro Hospitalar do Porto and UMIB, ICBAS, Universidade do Porto, Portugal;&#xD;
&#xD;
        -  Prof. Cervera Ricard - Dr. Espinosa Gerard, Dr. Ignasi Rodriguez - Department of&#xD;
           Autoimmune Diseases, Hospital Clinic, IDIBAPS, University of Barcelona - Spain;&#xD;
&#xD;
        -  Prof. Bertsias George - Dr. Nikos Kougkas - Department of Rheumatology, Clinical&#xD;
           Immunology and Allergy, University of Crete School of Medicine - Grece;&#xD;
&#xD;
        -  Patient Association delegates.&#xD;
&#xD;
      OPERATIVE STUDY DEVELOPMENT AND DATA ANALYSIS&#xD;
&#xD;
        1. BODI Development 1.1) Development of preliminary version of BODI (p-BODI) based on&#xD;
           literature review and inspired to pre-existing tools A preliminary list of damaged items&#xD;
           with respective definition will be generated after reviewing the literature and&#xD;
           preexisting damage indices (e.g VDI for vasculitides and SLICC damage index (SDI) for&#xD;
           systemic lupus erythematosus).&#xD;
&#xD;
           1.2) Reviewing and editing of the p-BODI by Delphi process A multi-step Delphi process,&#xD;
           based on reaching experts consensus, will be performed in order to review and refine the&#xD;
           p-BODI and the respective glossary. Through an online survey, each member EP will be&#xD;
           asked to rate: (a) how strongly they agree with the general rules for damage scoring;&#xD;
           (b) how strongly they agree to include the listed damage items within the BODI (e.g. to&#xD;
           which extent do you agree that &quot;Cataract&quot; should be included in the BODI?); (c) how&#xD;
           strongly they agree with the provided item definition. Ratings will be scored on a&#xD;
           5-point Likert scale (5 = strongly agree; 4 = agree; 3 = unsure; 2 = disagree; 1 =&#xD;
           strongly disagree). The EP members will be asked to give considerations and arguments to&#xD;
           support their opinion, especially if they score less than 4. They will also be given the&#xD;
           opportunity to suggest alternative wordings, to suggest additional items, or to make any&#xD;
           other comment.&#xD;
&#xD;
           In the reviewed p-BODI for the subsequent Delphi round, each issue (scoring rules,&#xD;
           damage items, item definitions) if: (a) ≥80% of EP members scores ≥4: will be included;&#xD;
           (b) 50-79% of EP members scores ≥4: will be included in the second questionnaire after&#xD;
           reviewing according to comments and suggestions provided in the previous round (c) &lt;50%&#xD;
           of EP members scores: will be excluded.&#xD;
&#xD;
           The WFG has the right to make alternative decisions after reviewing the EP responses&#xD;
           (e.g propose to change an item definition according to a suggestion from the expert&#xD;
           panel, even if the item was scored &gt;4 by ≥80% of EP).&#xD;
&#xD;
           An anonymous feedback report will be provided with the second questionnaire, in order to&#xD;
           offer the opportunity to reconsider and, if appropriate, to change a previous opinion in&#xD;
           light of the anonymous responses and considerations of the other EP members. The panel&#xD;
           members will again be asked to give their opinion on each issue in subsequent rounds&#xD;
           until complete consensus will be achieved (all issues scored ≥4 by ≥80% of EP) and the&#xD;
           definitive version of BODI will be developed.&#xD;
&#xD;
        2. Validation of BODI 2.1) Application of BODI on a multi-center cohort of BD patients Each&#xD;
           CG member will be asked to apply the reviewed version of BODI on a cohort of 30 BD&#xD;
           patients consecutively assessed in their own center. For Neurologist and&#xD;
           Ophthalmologist, the data from 10 consecutive patients will be enough. This is because&#xD;
           Neurologist and Ophthalmologist usually take care of the most severe neuropsychiatric&#xD;
           and ocular cases, which might bias the real prevalence of these manifestations in the&#xD;
           study cohort.&#xD;
&#xD;
      A multicenter cohort consisting of 200-250 BD patients will be thus set up. Patients will&#xD;
      undergo a routine clinical assessment, as scheduled in their follow-up program. No further&#xD;
      clinical, laboratory or instrumental investigations will be performed in addition to those&#xD;
      provided according to the good clinical practice. Any possible drug administration will be&#xD;
      evaluated independently from the study and according to the good clinical practice.&#xD;
&#xD;
      Inclusion criteria will be: a) BD diagnosis according to ICBD criteria, b) disease duration&#xD;
      ≥12 months), c) age at enrolment ≥ 18 years. For each recruited patient data will be&#xD;
      anonymously collected at the enrolment visit (T0). For patients with more than 5 years of&#xD;
      follow-up at the enrollment time, investigators will be further asked to perform a 5 years&#xD;
      retrospective BODI (Tr5). The following data will be collected (see the attached Case Report&#xD;
      Form):&#xD;
&#xD;
      - T1: demographics and medical history (gender; birthday, onset, diagnosis and enrolment&#xD;
      date; country of origin; ethnicity; comorbidity; smoker status); cumulative clinical&#xD;
      manifestation from onset to enrolment (oral aphthosis, genital aphthosis, skin lesions,&#xD;
      ocular involvement, neurologic lesions, vascular lesions, pathergy test, arthritis,&#xD;
      gastrointestinal manifestations); active clinical manifestations the enrolment visit; ongoing&#xD;
      and past therapy; BD current activity form (BDCAF); BODI; VDI; Physician global assessment&#xD;
      (PGA)on visual analogic scale; Patients global assessment (PtGA) on visual analogic scale;&#xD;
      Short Form 36 (SF-36) Health Survey,&#xD;
&#xD;
      • Tr5 (retrospectively): BODI&#xD;
&#xD;
      2.2) Assessment of face, content, construct, criterion validity and sensitivity to change&#xD;
      Validation will be performed according to the principles of OMERACT Filter 2.0, thus&#xD;
      according to the criteria of (A) truth, (B) discrimination and (C) feasibility will be&#xD;
      assessed.&#xD;
&#xD;
      A.1. Face validity. Since BODI will be developed through literature review and consensus&#xD;
      between an expert in BD management, face validity criteria should be automatically met.&#xD;
      However, face validity will be further tested by asking each CG member to complete a&#xD;
      questionnaire investigating the suitability of the tool.&#xD;
&#xD;
      A.2. Content validity. To assure content validity, the presence of damage identified by CG&#xD;
      but not classifiable in BODI will be assessed. Content validity will be further tested by&#xD;
      asking each CG member to complete a questionnaire relating to the comprehensiveness of the&#xD;
      instrument.&#xD;
&#xD;
      A.3. Construct validity. It will be assessed analyzing the agreement between results of&#xD;
      damage assessment on our validation cohort by BODI and other damage assessment tool. Since&#xD;
      there are no other specific and validate instruments for damage amassment in Behçet disease,&#xD;
      SLICC and VDI will be used as a surrogate. Correlation between the different indices results&#xD;
      will be evaluated by Pearson's or Spearman's correlation coefficients.&#xD;
&#xD;
      A.4. Criterion Validity. Criterion validity represents the correlation with results of&#xD;
      measurement with the new tool and other long-term outcomes related to the phenomenon we are&#xD;
      measuring. Since we expect that damage correlates with quality of life, disability and&#xD;
      mortality, a correlation between BODI score and SF-36, HAQ and in the future also with&#xD;
      mortality rate will be assessed.&#xD;
&#xD;
      B.1. Reliability. Clinical vignettes will be created from real cases to test the reliability&#xD;
      of the BODI. Thus, inter-observer agreement (kappa) will be assessed by asking a physician&#xD;
      from every center to assess the same clinical vignettes.&#xD;
&#xD;
      B.2. Sensitivity to change. The ability of the BODI to record the accumulation of damage over&#xD;
      time will be examined by determining the change in BODI score over 5 years of follow-up on&#xD;
      the validation cohort. The average increase of BODI score from T1 to T2 will be calculated&#xD;
      and will be tested by the Mann-Whitney test.&#xD;
&#xD;
      C. Feasibility. To test feasibility each CG member will be asked to complete a questionnaire&#xD;
      relating to the ease of use, consumption of time and interpretability of the instrument.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">August 1, 2017</start_date>
  <completion_date type="Anticipated">December 2019</completion_date>
  <primary_completion_date type="Anticipated">June 2019</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>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Behçet's disease Overall Damage Index</measure>
    <time_frame>Baseline</time_frame>
    <description>Prevalence and type of organ damage in Behçet's Disease assessed by experimental tool</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Vasculitis Damage Index</measure>
    <time_frame>Baseline</time_frame>
    <description>Prevalence and type of organ damage in Behçet's Disease assessed by non specific tool different</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease activity (Behçet disease actvity form)</measure>
    <time_frame>Baseline</time_frame>
    <description>Prevalence and level of disease activity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health Related Quality of Life (HRQoL)</measure>
    <time_frame>Baseline</time_frame>
    <description>Health Related Quality of Life measured by the eight scaled scores of the SF-36: 1) vitality; 2) physical functioning; 3) bodily pain; 4) general health perceptions; 5) physical role functioning; 6) emotional role functioning; 7) social role functioning; 8) mental health. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability</description>
  </secondary_outcome>
  <enrollment type="Anticipated">210</enrollment>
  <condition>Behçet Disease</condition>
  <condition>Behcet's Disease Aggravated</condition>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Behçet's disease Overall Damage Index (BODI)</intervention_name>
    <description>BODI is a tool to document any organ damage that has occurred in patients since the onset of BD. It includes a form and an associated glossary with the definition of the items.</description>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        A multicenter cohort consisting of 200-250 consecutive BD patients. Each participating&#xD;
        investigator will enroll a cohort of 20-30 BD patients consecutively assessed in its own&#xD;
        center.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  BD diagnosis according to ICBD criteria;&#xD;
&#xD;
          -  disease duration ≥12 months;&#xD;
&#xD;
          -  age at enrolment ≥ 18 years;&#xD;
&#xD;
          -  Able to understand and voluntarily sign informed consent forms (ICFs) prior to the&#xD;
             initiation of any study-specific assessments/procedures.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  unable to adhere to the protocol requirements.&#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>Matteo Piga, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Azienda Ospedaliero Universitaria Cagliari</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Matteo Piga, MD</last_name>
    <phone>+390706754069</phone>
    <email>matteopiga@unica.it</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Alberto Floris, MD</last_name>
    <phone>+3907051093348</phone>
    <email>albertofloris1@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Department of Rheumatology, Clinical Immunology and Allergy, University of Crete</name>
      <address>
        <city>Heraklion</city>
        <country>Greece</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>George Bertsias, Prof</last_name>
    </contact>
    <contact_backup>
      <last_name>Nikos Cougas</last_name>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Rheumatology Unit, University of Bari</name>
      <address>
        <city>Bari</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Florenzo Iannone</last_name>
    </contact>
    <contact_backup>
      <last_name>Giuseppe Lopalco</last_name>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Rheumatology Unit, Department of Clinical Sciences, AOU Sant'Anna University of Ferrara</name>
      <address>
        <city>Ferrara</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Govoni Marcello</last_name>
    </contact>
    <contact_backup>
      <last_name>Andrea Lo Monaco</last_name>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Patient Association Delegates</name>
      <address>
        <city>Iglesias</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero Universitaria Cagliari</name>
      <address>
        <city>Monserrato</city>
        <zip>09042</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alessandro Mathieu</last_name>
      <phone>07051093340</phone>
      <email>amah@unica.it</email>
    </contact>
    <contact_backup>
      <last_name>Alberto Cauli</last_name>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Rheumatology Unit, Policlinico Le Scotte, University of Siena</name>
      <address>
        <city>Siena</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Luca Cantarini</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Clinical Immunology Unit, Centro Hospitalar do Porto, Universidade do Porto</name>
      <address>
        <city>Porto</city>
        <country>Portugal</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Joao Correia, Dr.</last_name>
    </contact>
    <contact_backup>
      <last_name>Raquel Faria</last_name>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Neurology Department, Hospital Santo Antonio, Centro Hospitalar do Porto</name>
      <address>
        <city>Porto</city>
        <country>Portugal</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ana Martin Silva, Dr.</last_name>
    </contact>
    <contact_backup>
      <last_name>Ernestina Santos</last_name>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Department of Autoimmune Diseases, Hospital Clinic, University of Barcelona</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ricard Cervera, Prof.</last_name>
    </contact>
    <contact_backup>
      <last_name>Gerard Espinosa, Dr.</last_name>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Eye Institute at Cleveland Clinic</name>
      <address>
        <city>Abu Dhabi</city>
        <country>United Arab Emirates</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location_countries>
    <country>Greece</country>
    <country>Italy</country>
    <country>Portugal</country>
    <country>Spain</country>
    <country>United Arab Emirates</country>
  </location_countries>
  <reference>
    <citation>Hatemi G, Merkel PA, Hamuryudan V, Boers M, Direskeneli H, Aydin SZ, Yazici H. Outcome measures used in clinical trials for Behcet syndrome: a systematic review. J Rheumatol. 2014 Mar;41(3):599-612. doi: 10.3899/jrheum.131249. Epub 2014 Feb 1.</citation>
    <PMID>24488418</PMID>
  </reference>
  <reference>
    <citation>Hatemi G, Meara A, Ozguler Y, Direskeneli H, Mahr A, Easley E, Gurcan M, Davis T, Gul A, Yazici Y, Zottenberg K, Esatoglu SN, Erer B, Kamali S, Yazici H, Cronholm PF, Merkel PA. Developing a Core Set of Outcome Measures for Behcet Disease: Report from OMERACT 2016. J Rheumatol. 2017 Nov;44(11):1750-1753. doi: 10.3899/jrheum.161352. Epub 2017 Apr 1.</citation>
    <PMID>28365574</PMID>
  </reference>
  <reference>
    <citation>Piga M, Mathieu A. The origin of Behcet's disease geoepidemiology: possible role of a dual microbial-driven genetic selection. Clin Exp Rheumatol. 2014 Jul-Aug;32(4 Suppl 84):S123-9. Epub 2014 Jan 20.</citation>
    <PMID>24447390</PMID>
  </reference>
  <reference>
    <citation>Kirwan JR, Boers M, Tugwell P. Updating the OMERACT filter at OMERACT 11. J Rheumatol. 2014 May;41(5):975-7. doi: 10.3899/jrheum.131306.</citation>
    <PMID>24788466</PMID>
  </reference>
  <reference>
    <citation>Wells G, Beaton DE, Tugwell P, Boers M, Kirwan JR, Bingham CO 3rd, Boonen A, Brooks P, Conaghan PG, D'Agostino MA, Dougados M, Furst DE, Gossec L, Guillemin F, Helliwell P, Hewlett S, Kvien TK, Landewe RB, March L, Mease PJ, Ostergaard M, Simon L, Singh JA, Strand V, van der Heijde DM. Updating the OMERACT filter: discrimination and feasibility. J Rheumatol. 2014 May;41(5):1005-10. doi: 10.3899/jrheum.131311. Epub 2014 Apr 1.</citation>
    <PMID>24692522</PMID>
  </reference>
  <reference>
    <citation>Exley AR, Bacon PA, Luqmani RA, Kitas GD, Gordon C, Savage CO, Adu D. Development and initial validation of the Vasculitis Damage Index for the standardized clinical assessment of damage in the systemic vasculitides. Arthritis Rheum. 1997 Feb;40(2):371-80. doi: 10.1002/art.1780400222.</citation>
    <PMID>9041949</PMID>
  </reference>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 10, 2019</study_first_submitted>
  <study_first_submitted_qc>January 10, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 14, 2019</study_first_posted>
  <last_update_submitted>January 13, 2019</last_update_submitted>
  <last_update_submitted_qc>January 13, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 15, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Cagliari</investigator_affiliation>
    <investigator_full_name>Matteo Piga</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>Damage</keyword>
  <keyword>Outcome measure</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Behcet Syndrome</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>De-identified individual participant data for all outcome measures will be made available.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>.Within 6 months of study completion.</ipd_time_frame>
    <ipd_access_criteria>Upon request</ipd_access_criteria>
  </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/NCT03803462
org study id: BODI
nct id: NCT03803462
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Damage in vasculitis, as well as in other chronic inflammatory disorders, accrues over time
      resulting in impairment of quality of life, development of disability and increased
      mortality. For these reasons, damage represents an important outcome to be assessed and
      measured both in trials and clinical practice.

      Currently, the most widely used assessment tool for damage in vasculitis is the Vasculitis
      Damage Index (VDI). However, VDI was developed for a no specific type of vasculitis and it
      appears to be more suitable for damage assessment in ANCA-associated vasculitis than in
      Behçet' disease (BD).

      BD is a chronic and multisystem inflammatory disorder classified among vasculitides. As well
      as in other vasculitides, disease activity and treatment in BD can result in the development
      and accumulation of irreversible organ damage, such as blindness, tissue loss and a wide
      range of neurologic disorders. Recently the OMERACT has defined the Core Set domain of
      Outcome Measures for BD. Despite damage is included in the OMERACT outcome core set for
      rheumatic disease, a specific assessment tool for BD is currently not available.

      The aim of this study is to develop and validate the first tool for describing and measuring
      organ damage in patients with Behçet Disease (Behçet's disease Overall Damage index - BODI).
DESIGN OF THE STUDY

      This observational multicenter study will be developed in 2 subsequent phases, in their turn,
      consisting of different steps (figure 1):

        1. BODI Development 1.1) Development of a preliminary version of BODI (p-BODI) based on
           literature review and inspired by pre-existing tools according to OMERACT guidelines;
           1.2) Delphi process aimed to review and improve the p-BODI.

        2. Validation of the new tool according to OMERACT filter 2.0 2.1) Application of the BODI
           on a multicentre cohort of BD patients. 2.2) Assessment of face, content, construct and
           criterion validity, and sensitivity to change.

      2.3) Assessment of reliability based on scoring exercise on clinical vignettes.

      All subjects involved in the study are experts in the management of BD. They will work in two
      different groups having different roles:

        -  Work and facilitator group (WFG): consisting of 3 Physician from the Coordinating
           Centre. The tasks of the WFG are: (a) to review literature and develop a preliminary
           version of BODI (p-BODI), including: definition of damage, rules for scoring and
           identification of potential items of damage; (b) to coordinate the Delphi process for
           editing and optimizing p-BODI; (c) to analyse data from the validation process.

        -  Expert Panel (EP): consisting of multidisciplinary experts in Behçet's disease and
           Patient's delegate from different countries. EP members will be selected and invited to
           participate in the study by the WFG. The tasks of the EP are to express their opinion on
           p-BODI and propose editing for its improvement within a Delphi process;

        -  Clinicians group (CG): consisting of one Clinician from each Centre, with expertise in
           Behçet's disease but not involved in the Delphi process. The tasks of this group are:
           (a) to apply the BODI on 30 consecutive patients with BD (10 for Neurologist and
           Ophthalmologist) from each Centre involved in the study; (b) to score a set of clinical
           vignettes using the BODI, to assess reliability of the instrument; (c) to express an
           overall judgement (in an online survey) regarding to general credibility,
           comprehensiveness and feasibility of the BODI.

      The member of EP and GC, involved in the study so far, with respective affiliations, are
      reported below:

      EP members - CG members - Affiliations.

        -  Prof. Alessandro Mathieu - Dr. Matteo Piga - Chair and Unit of Rheumatology, University
           and AOU of Cagliari, Monserrato - Italy;

        -  Prof. Govoni Marcello - Dr. Lo Monaco Andrea - Department of Medical Sciences, Section
           of Rheumatology, AOU S. Anna, the University of Ferrara - Italy;

        -  Prof. Iannone Florenzo - Dr. Lopalco Giuseppe - Department of Emergency and Organ
           Transplantation, Rheumatology Unit, University of Bari - Italy;

        -  Prof. Neri Piergiorgio - Dr. Pirani Vittorio - Ocular Immunology Service, the Eye
           Clinic, Polytechnic University of Marche- Ancona - Italy;

        -  Prof. Cantarini Luca - Dr. Orlando Ida - Rheumatology Unit, University of Siena.
           Policlinico Le Scotte;

        -  Prof. Martins Silva Ana - Dr. Santos Ernestina - Neurology Department, Hospital Santo
           António, Centro Hospitalar do Porto - Portugal;

        -  Prof. Vasconcelos Carlos - Prof Correia Joao; Dr. Raquel Faria - Clinical Immunology
           Unit, Centro Hospitalar do Porto and UMIB, ICBAS, Universidade do Porto, Portugal;

        -  Prof. Cervera Ricard - Dr. Espinosa Gerard, Dr. Ignasi Rodriguez - Department of
           Autoimmune Diseases, Hospital Clinic, IDIBAPS, University of Barcelona - Spain;

        -  Prof. Bertsias George - Dr. Nikos Kougkas - Department of Rheumatology, Clinical
           Immunology and Allergy, University of Crete School of Medicine - Grece;

        -  Patient Association delegates.

      OPERATIVE STUDY DEVELOPMENT AND DATA ANALYSIS

        1. BODI Development 1.1) Development of preliminary version of BODI (p-BODI) based on
           literature review and inspired to pre-existing tools A preliminary list of damaged items
           with respective definition will be generated after reviewing the literature and
           preexisting damage indices (e.g VDI for vasculitides and SLICC damage index (SDI) for
           systemic lupus erythematosus).

           1.2) Reviewing and editing of the p-BODI by Delphi process A multi-step Delphi process,
           based on reaching experts consensus, will be performed in order to review and refine the
           p-BODI and the respective glossary. Through an online survey, each member EP will be
           asked to rate: (a) how strongly they agree with the general rules for damage scoring;
           (b) how strongly they agree to include the listed damage items within the BODI (e.g. to
           which extent do you agree that "Cataract" should be included in the BODI?); (c) how
           strongly they agree with the provided item definition. Ratings will be scored on a
           5-point Likert scale (5 = strongly agree; 4 = agree; 3 = unsure; 2 = disagree; 1 =
           strongly disagree). The EP members will be asked to give considerations and arguments to
           support their opinion, especially if they score less than 4. They will also be given the
           opportunity to suggest alternative wordings, to suggest additional items, or to make any
           other comment.

           In the reviewed p-BODI for the subsequent Delphi round, each issue (scoring rules,
           damage items, item definitions) if: (a) ≥80% of EP members scores ≥4: will be included;
           (b) 50-79% of EP members scores ≥4: will be included in the second questionnaire after
           reviewing according to comments and suggestions provided in the previous round (c) <50%
           of EP members scores: will be excluded.

           The WFG has the right to make alternative decisions after reviewing the EP responses
           (e.g propose to change an item definition according to a suggestion from the expert
           panel, even if the item was scored >4 by ≥80% of EP).

           An anonymous feedback report will be provided with the second questionnaire, in order to
           offer the opportunity to reconsider and, if appropriate, to change a previous opinion in
           light of the anonymous responses and considerations of the other EP members. The panel
           members will again be asked to give their opinion on each issue in subsequent rounds
           until complete consensus will be achieved (all issues scored ≥4 by ≥80% of EP) and the
           definitive version of BODI will be developed.

        2. Validation of BODI 2.1) Application of BODI on a multi-center cohort of BD patients Each
           CG member will be asked to apply the reviewed version of BODI on a cohort of 30 BD
           patients consecutively assessed in their own center. For Neurologist and
           Ophthalmologist, the data from 10 consecutive patients will be enough. This is because
           Neurologist and Ophthalmologist usually take care of the most severe neuropsychiatric
           and ocular cases, which might bias the real prevalence of these manifestations in the
           study cohort.

      A multicenter cohort consisting of 200-250 BD patients will be thus set up. Patients will
      undergo a routine clinical assessment, as scheduled in their follow-up program. No further
      clinical, laboratory or instrumental investigations will be performed in addition to those
      provided according to the good clinical practice. Any possible drug administration will be
      evaluated independently from the study and according to the good clinical practice.

      Inclusion criteria will be: a) BD diagnosis according to ICBD criteria, b) disease duration
      ≥12 months), c) age at enrolment ≥ 18 years. For each recruited patient data will be
      anonymously collected at the enrolment visit (T0). For patients with more than 5 years of
      follow-up at the enrollment time, investigators will be further asked to perform a 5 years
      retrospective BODI (Tr5). The following data will be collected (see the attached Case Report
      Form):

      - T1: demographics and medical history (gender; birthday, onset, diagnosis and enrolment
      date; country of origin; ethnicity; comorbidity; smoker status); cumulative clinical
      manifestation from onset to enrolment (oral aphthosis, genital aphthosis, skin lesions,
      ocular involvement, neurologic lesions, vascular lesions, pathergy test, arthritis,
      gastrointestinal manifestations); active clinical manifestations the enrolment visit; ongoing
      and past therapy; BD current activity form (BDCAF); BODI; VDI; Physician global assessment
      (PGA)on visual analogic scale; Patients global assessment (PtGA) on visual analogic scale;
      Short Form 36 (SF-36) Health Survey,

      • Tr5 (retrospectively): BODI

      2.2) Assessment of face, content, construct, criterion validity and sensitivity to change
      Validation will be performed according to the principles of OMERACT Filter 2.0, thus
      according to the criteria of (A) truth, (B) discrimination and (C) feasibility will be
      assessed.

      A.1. Face validity. Since BODI will be developed through literature review and consensus
      between an expert in BD management, face validity criteria should be automatically met.
      However, face validity will be further tested by asking each CG member to complete a
      questionnaire investigating the suitability of the tool.

      A.2. Content validity. To assure content validity, the presence of damage identified by CG
      but not classifiable in BODI will be assessed. Content validity will be further tested by
      asking each CG member to complete a questionnaire relating to the comprehensiveness of the
      instrument.

      A.3. Construct validity. It will be assessed analyzing the agreement between results of
      damage assessment on our validation cohort by BODI and other damage assessment tool. Since
      there are no other specific and validate instruments for damage amassment in Behçet disease,
      SLICC and VDI will be used as a surrogate. Correlation between the different indices results
      will be evaluated by Pearson's or Spearman's correlation coefficients.

      A.4. Criterion Validity. Criterion validity represents the correlation with results of
      measurement with the new tool and other long-term outcomes related to the phenomenon we are
      measuring. Since we expect that damage correlates with quality of life, disability and
      mortality, a correlation between BODI score and SF-36, HAQ and in the future also with
      mortality rate will be assessed.

      B.1. Reliability. Clinical vignettes will be created from real cases to test the reliability
      of the BODI. Thus, inter-observer agreement (kappa) will be assessed by asking a physician
      from every center to assess the same clinical vignettes.

      B.2. Sensitivity to change. The ability of the BODI to record the accumulation of damage over
      time will be examined by determining the change in BODI score over 5 years of follow-up on
      the validation cohort. The average increase of BODI score from T1 to T2 will be calculated
      and will be tested by the Mann-Whitney test.

      C. Feasibility. To test feasibility each CG member will be asked to complete a questionnaire
      relating to the ease of use, consumption of time and interpretability of the instrument.
observational model: Cohort
time perspective: Cross-Sectional
measure: Behçet's disease Overall Damage Index
time frame: Baseline
description: Prevalence and type of organ damage in Behçet's Disease assessed by experimental tool
measure: Vasculitis Damage Index
time frame: Baseline
description: Prevalence and type of organ damage in Behçet's Disease assessed by non specific tool different
measure: Disease activity (Behçet disease actvity form)
time frame: Baseline
description: Prevalence and level of disease activity
measure: Health Related Quality of Life (HRQoL)
time frame: Baseline
description: Health Related Quality of Life measured by the eight scaled scores of the SF-36: 1) vitality; 2) physical functioning; 3) bodily pain; 4) general health perceptions; 5) physical role functioning; 6) emotional role functioning; 7) social role functioning; 8) mental health. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability
intervention type: Other
intervention name: Behçet's disease Overall Damage Index (BODI)
description: BODI is a tool to document any organ damage that has occurred in patients since the onset of BD. It includes a form and an associated glossary with the definition of the items.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Matteo Piga, MD
role: Principal Investigator
affiliation: Azienda Ospedaliero Universitaria Cagliari
last name: Matteo Piga, MD
phone: +390706754069
email: matteopiga@unica.it
last name: Alberto Floris, MD
phone: +3907051093348
email: albertofloris1@gmail.com
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Active, not recruiting
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Active, not recruiting
country: Greece
country: Italy
country: Portugal
country: Spain
country: United Arab Emirates
citation: Hatemi G, Merkel PA, Hamuryudan V, Boers M, Direskeneli H, Aydin SZ, Yazici H. Outcome measures used in clinical trials for Behcet syndrome: a systematic review. J Rheumatol. 2014 Mar;41(3):599-612. doi: 10.3899/jrheum.131249. Epub 2014 Feb 1.
PMID: 24488418
citation: Hatemi G, Meara A, Ozguler Y, Direskeneli H, Mahr A, Easley E, Gurcan M, Davis T, Gul A, Yazici Y, Zottenberg K, Esatoglu SN, Erer B, Kamali S, Yazici H, Cronholm PF, Merkel PA. Developing a Core Set of Outcome Measures for Behcet Disease: Report from OMERACT 2016. J Rheumatol. 2017 Nov;44(11):1750-1753. doi: 10.3899/jrheum.161352. Epub 2017 Apr 1.
PMID: 28365574
citation: Piga M, Mathieu A. The origin of Behcet's disease geoepidemiology: possible role of a dual microbial-driven genetic selection. Clin Exp Rheumatol. 2014 Jul-Aug;32(4 Suppl 84):S123-9. Epub 2014 Jan 20.
PMID: 24447390
citation: Kirwan JR, Boers M, Tugwell P. Updating the OMERACT filter at OMERACT 11. J Rheumatol. 2014 May;41(5):975-7. doi: 10.3899/jrheum.131306.
PMID: 24788466
citation: Wells G, Beaton DE, Tugwell P, Boers M, Kirwan JR, Bingham CO 3rd, Boonen A, Brooks P, Conaghan PG, D'Agostino MA, Dougados M, Furst DE, Gossec L, Guillemin F, Helliwell P, Hewlett S, Kvien TK, Landewe RB, March L, Mease PJ, Ostergaard M, Simon L, Singh JA, Strand V, van der Heijde DM. Updating the OMERACT filter: discrimination and feasibility. J Rheumatol. 2014 May;41(5):1005-10. doi: 10.3899/jrheum.131311. Epub 2014 Apr 1.
PMID: 24692522
citation: Exley AR, Bacon PA, Luqmani RA, Kitas GD, Gordon C, Savage CO, Adu D. Development and initial validation of the Vasculitis Damage Index for the standardized clinical assessment of damage in the systemic vasculitides. Arthritis Rheum. 1997 Feb;40(2):371-80. doi: 10.1002/art.1780400222.
PMID: 9041949
responsible party type: Principal Investigator
investigator affiliation: University of Cagliari
investigator full name: Matteo Piga
investigator title: Assistant Professor
mesh term: Behcet Syndrome
sharing ipd: Yes
ipd description: De-identified individual participant data for all outcome measures will be made available.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: .Within 6 months of study completion.
ipd access criteria: Upon request