<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/NCT02232321</url>
  </required_header>
  <id_info>
    <org_study_id>PsA-MDA</org_study_id>
    <nct_id>NCT02232321</nct_id>
  </id_info>
  <brief_title>Vascular Effects of Achieving Minimal Disease Activity in Psoriatic Arthritis - a 2 Year Prospective Cohort Study</brief_title>
  <official_title>Vascular Effects of Achieving Minimal Disease Activity in Psoriatic Arthritis - a 2 Year Prospective Cohort Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chinese University of Hong Kong</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chinese University of Hong Kong</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Objectives To investigate the effect of achieving minimal disease activity (MDA) using a&#xD;
      protocolized treatment strategy on the progression of subclinical atherosclerosis and&#xD;
      arterial stiffness in psoriatic arthritis (PsA) patients.&#xD;
&#xD;
      Hypothesis Effective suppression of inflammation in patients who can achieve MDA will have&#xD;
      less progression of subclinical atherosclerosis and arterial stiffness then patients who&#xD;
      cannot achieve MDA by means of a standardized treatment algorithm aiming at MDA.&#xD;
&#xD;
      Design and subjects One hundred consecutive PsA patients will participate in this 2-year&#xD;
      prospective, hospital-based, cohort study.&#xD;
&#xD;
      Interventions All participants will receive 2-year tight-control treatment. Treatment will be&#xD;
      adjusted according to a standardized protocol based on the European League Against Rheumatism&#xD;
      (EULAR) recommendation and the Hong Kong guideline on the use of biologics every 4-monthly&#xD;
      aiming at MDA.&#xD;
&#xD;
      Study instruments Carotid intima-media thickness (IMT) will be measured using high-resolution&#xD;
      ultrasound. Arterial stiffness is measured using pulse wave velocity (PWV) by a dedicated&#xD;
      tonometry system and augmentation index (AIx) by the SphygmoCor device.&#xD;
&#xD;
      Main outcome measures and analysis The main outcome measure is the change in IMT over a&#xD;
      period of 2 years comparing between patients who achieve MDA at 12 months (MDA group) to&#xD;
      those who cannot achieve MDA (non-MDA group). Secondary outcomes include differences in the&#xD;
      changes in AIx and PWV over 2 years between the 2 groups. Comparisons of the changes in IMT,&#xD;
      AIx and PWV over 2 years between the MDA and non-MDA groups will be performed.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background:&#xD;
&#xD;
      Patients with psoriatic arthritis (PsA) experience substantial morbidity and unfavorable&#xD;
      outcomes at referral centers. Although studies on all-cause mortality have yielded mixed&#xD;
      results, increased cardiovascular (CV) mortality and morbidity in PsA have been consistently&#xD;
      reported. Data from our group and others have shown that underlying these higher CV disease&#xD;
      (CVD) rates is a greater burden of subclinical carotid atherosclerosis. Increased&#xD;
      intima-media thickness (IMT) significantly correlates with traditional risk factors and&#xD;
      disease-related parameters. An increased prevalence of arterial stiffness has also been&#xD;
      demonstrated in patients with psoriasis and PsA compared with controls. In PsA, criteria for&#xD;
      minimal disease activity (MDA) have been developed and validated. These criteria use 7&#xD;
      measurements including entheseal and skin assessments. Achieving MDA by these criteria&#xD;
      results in less radiographic damage in the long term. The development of this instrument is a&#xD;
      step toward 'treatment to target' in PsA. MDA is achieved in 48-60% of patients at ≥ 1 visit,&#xD;
      and is sustained for ≥ 12 months (sustained MDA) in at least one third of PsA patients in a&#xD;
      large observational cohort.&#xD;
&#xD;
      While achieving MDA may result in significant benefits in articular disease, little is known&#xD;
      about its effect on extra-articular disease, including CVD risk. The use of surrogate end&#xD;
      points instead of actual CV events may provide more evidence on whether PsA patients may&#xD;
      benefit from potent anti-inflammatory treatment on the prevention of premature&#xD;
      atherosclerosis. Data from our group and others linked the suppression of inflammation using&#xD;
      anti-tumour necrosis factor (anti-TNF) with a favourable effect on CV surrogate makers,&#xD;
      including carotid IMT and arterial stiffness. More recently, a tight-control treatment&#xD;
      strategy aiming at remission was effective in improving arterial stiffness in our early&#xD;
      rheumatoid arthritis (RA) cohort. There is an imperative need for interventional trials with&#xD;
      CV end points to investigate whether achievement of MDA by a protocolized treatment strategy&#xD;
      could reduce CVD risk in PsA. To fill in these gaps of knowledge, we propose a prospective&#xD;
      cohort study to ascertain whether achieving MDA through a protocolized treatment strategy may&#xD;
      prevent long term progression of IMT and arterial stiffness to a greater extent than those&#xD;
      who cannot achieve MDA in patients with PsA.&#xD;
&#xD;
      Aim of the study:&#xD;
&#xD;
      Primary outcome:&#xD;
&#xD;
      1. Effect of achieving MDA (MDA group) at 12 months on the progression of subclinical&#xD;
      atherosclerosis over a period of 24 months as evaluated by IMT compared to those who cannot&#xD;
      achieve MDA (non-MDA group)&#xD;
&#xD;
      Secondary outcomes:&#xD;
&#xD;
        1. Changes in arterial stiffness over a period of 24 months as evaluated by pulse wave&#xD;
           velocity (PWV) and augmentation Index (AIx) between the MDA group and non-MDA group.&#xD;
&#xD;
        2. The proportion of patients achieving sustained MDA (from 12 to 24 months)&#xD;
&#xD;
        3. Changes in IMT and arterial stiffness over a period of 24 months as evaluated by IMT,&#xD;
           PWV and AIx between patients who can achieve sustained MDA and those who cannot achieve&#xD;
           sustained MDA.&#xD;
&#xD;
        4. Correlations between the changes in IMT, PWV, and AIX and the changes in markers of&#xD;
           disease activity&#xD;
&#xD;
      Hypothesis:&#xD;
&#xD;
      Effective suppression of inflammation in PsA patients who can achieve MDA will have less&#xD;
      progression of subclinical atherosclerosis and arterial stiffness than patients who cannot&#xD;
      achieve MDA by means of a protocolized treatment algorithm&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>March 2014</start_date>
  <completion_date type="Actual">May 2018</completion_date>
  <primary_completion_date type="Actual">October 2017</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>PsA MDA and subclinical atherosclerosis</measure>
    <time_frame>30 months</time_frame>
    <description>Effect of achieving MDA (MDA group) at 12 months on the progression of subclinical atherosclerosis over a period of 24 months as evaluated by IMT compared to those who cannot achieve MDA (non-MDA group).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PsA MDA and arterial stiffness</measure>
    <time_frame>30 months</time_frame>
    <description>Changes in arterial stiffness over a period of 24 months as evaluated by pulse wave velocity (PWV) and augmentation Index (AIx) between the MDA group and non-MDA group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PsA MDA rate</measure>
    <time_frame>30 months</time_frame>
    <description>The proportion of patients achieving sustained MDA (from 12 to 24 months)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PsA sustained MDA and atherosclerosis and arterial stiffness</measure>
    <time_frame>30 month</time_frame>
    <description>Changes in IMT and arterial stiffness over a period of 24 months as evaluated by IMT, PWV and AIx between patients who can achieve sustained MDA and those who cannot achieve sustained MDA.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PsA atherosclerosis and arterial stiffness</measure>
    <time_frame>30 months</time_frame>
    <description>Correlations between the changes in IMT, PWV, and AIX and the changes in markers of disease activity</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">113</enrollment>
  <condition>Psoriatic Arthritis</condition>
  <condition>Atherosclerosis</condition>
  <condition>Arterial Stiffness</condition>
  <arm_group>
    <arm_group_label>PsA MDA</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>PsA MDA</intervention_name>
    <arm_group_label>PsA MDA</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  PsA attending the outpatient clinic of the Prince of Wales Hospital (PWH) who&#xD;
             fulfilled the Classification of Psoriatic Arthritis criteria&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  1) have a history of overt CVD (myocardial infarction, percutaneous transluminal&#xD;
             coronary angioplasty, surgery for ischemic heart disease, stroke, transient ischemic&#xD;
             attack, carotid endarterectomy, peripheral arterial reconstructive surgery, or limb&#xD;
             amputation), or 2) are on aspirin, or HMG-CoA reductase inhibitors (statins) or&#xD;
             angiotensin-converting-enzyme inhibitor (ACEI), or 3) have significant co-morbidities&#xD;
             including severe renal impairment defined as a glomerular filtration rate of less than&#xD;
             30 mL/min/1.73m2, alanine aminotransferase (ALT) ≥2xULN, hemoglobin level &lt;8.5gm/dl,&#xD;
             white blood cell count &lt;3.5x109/liter, platelet count&lt;100x109/liter, or 4) female of&#xD;
             childbearing potential who are unwilling to use adequate contraception, pregnant or&#xD;
             breastfeeding women, or 5) they are on glucocorticoids at a dose &gt;10mg/day (equivalent&#xD;
             dose of prednisolone)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Prince of Wales Hospital</name>
      <address>
        <city>Hong Kong</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>September 2, 2014</study_first_submitted>
  <study_first_submitted_qc>September 2, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 5, 2014</study_first_posted>
  <last_update_submitted>July 17, 2018</last_update_submitted>
  <last_update_submitted_qc>July 17, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">July 19, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Chinese University of Hong Kong</investigator_affiliation>
    <investigator_full_name>Lai-Shan Tam</investigator_full_name>
    <investigator_title>Professor</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>
    <mesh_term>Atherosclerosis</mesh_term>
  </condition_browse>
  <!-- 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/NCT02232321
org study id: PsA-MDA
nct id: NCT02232321
lead sponsor: 
has dmc: No
Objectives To investigate the effect of achieving minimal disease activity (MDA) using a
      protocolized treatment strategy on the progression of subclinical atherosclerosis and
      arterial stiffness in psoriatic arthritis (PsA) patients.

      Hypothesis Effective suppression of inflammation in patients who can achieve MDA will have
      less progression of subclinical atherosclerosis and arterial stiffness then patients who
      cannot achieve MDA by means of a standardized treatment algorithm aiming at MDA.

      Design and subjects One hundred consecutive PsA patients will participate in this 2-year
      prospective, hospital-based, cohort study.

      Interventions All participants will receive 2-year tight-control treatment. Treatment will be
      adjusted according to a standardized protocol based on the European League Against Rheumatism
      (EULAR) recommendation and the Hong Kong guideline on the use of biologics every 4-monthly
      aiming at MDA.

      Study instruments Carotid intima-media thickness (IMT) will be measured using high-resolution
      ultrasound. Arterial stiffness is measured using pulse wave velocity (PWV) by a dedicated
      tonometry system and augmentation index (AIx) by the SphygmoCor device.

      Main outcome measures and analysis The main outcome measure is the change in IMT over a
      period of 2 years comparing between patients who achieve MDA at 12 months (MDA group) to
      those who cannot achieve MDA (non-MDA group). Secondary outcomes include differences in the
      changes in AIx and PWV over 2 years between the 2 groups. Comparisons of the changes in IMT,
      AIx and PWV over 2 years between the MDA and non-MDA groups will be performed.
Background:

      Patients with psoriatic arthritis (PsA) experience substantial morbidity and unfavorable
      outcomes at referral centers. Although studies on all-cause mortality have yielded mixed
      results, increased cardiovascular (CV) mortality and morbidity in PsA have been consistently
      reported. Data from our group and others have shown that underlying these higher CV disease
      (CVD) rates is a greater burden of subclinical carotid atherosclerosis. Increased
      intima-media thickness (IMT) significantly correlates with traditional risk factors and
      disease-related parameters. An increased prevalence of arterial stiffness has also been
      demonstrated in patients with psoriasis and PsA compared with controls. In PsA, criteria for
      minimal disease activity (MDA) have been developed and validated. These criteria use 7
      measurements including entheseal and skin assessments. Achieving MDA by these criteria
      results in less radiographic damage in the long term. The development of this instrument is a
      step toward 'treatment to target' in PsA. MDA is achieved in 48-60% of patients at ≥ 1 visit,
      and is sustained for ≥ 12 months (sustained MDA) in at least one third of PsA patients in a
      large observational cohort.

      While achieving MDA may result in significant benefits in articular disease, little is known
      about its effect on extra-articular disease, including CVD risk. The use of surrogate end
      points instead of actual CV events may provide more evidence on whether PsA patients may
      benefit from potent anti-inflammatory treatment on the prevention of premature
      atherosclerosis. Data from our group and others linked the suppression of inflammation using
      anti-tumour necrosis factor (anti-TNF) with a favourable effect on CV surrogate makers,
      including carotid IMT and arterial stiffness. More recently, a tight-control treatment
      strategy aiming at remission was effective in improving arterial stiffness in our early
      rheumatoid arthritis (RA) cohort. There is an imperative need for interventional trials with
      CV end points to investigate whether achievement of MDA by a protocolized treatment strategy
      could reduce CVD risk in PsA. To fill in these gaps of knowledge, we propose a prospective
      cohort study to ascertain whether achieving MDA through a protocolized treatment strategy may
      prevent long term progression of IMT and arterial stiffness to a greater extent than those
      who cannot achieve MDA in patients with PsA.

      Aim of the study:

      Primary outcome:

      1. Effect of achieving MDA (MDA group) at 12 months on the progression of subclinical
      atherosclerosis over a period of 24 months as evaluated by IMT compared to those who cannot
      achieve MDA (non-MDA group)

      Secondary outcomes:

        1. Changes in arterial stiffness over a period of 24 months as evaluated by pulse wave
           velocity (PWV) and augmentation Index (AIx) between the MDA group and non-MDA group.

        2. The proportion of patients achieving sustained MDA (from 12 to 24 months)

        3. Changes in IMT and arterial stiffness over a period of 24 months as evaluated by IMT,
           PWV and AIx between patients who can achieve sustained MDA and those who cannot achieve
           sustained MDA.

        4. Correlations between the changes in IMT, PWV, and AIX and the changes in markers of
           disease activity

      Hypothesis:

      Effective suppression of inflammation in PsA patients who can achieve MDA will have less
      progression of subclinical atherosclerosis and arterial stiffness than patients who cannot
      achieve MDA by means of a protocolized treatment algorithm
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: PsA MDA and subclinical atherosclerosis
time frame: 30 months
description: Effect of achieving MDA (MDA group) at 12 months on the progression of subclinical atherosclerosis over a period of 24 months as evaluated by IMT compared to those who cannot achieve MDA (non-MDA group).
measure: PsA MDA and arterial stiffness
time frame: 30 months
description: Changes in arterial stiffness over a period of 24 months as evaluated by pulse wave velocity (PWV) and augmentation Index (AIx) between the MDA group and non-MDA group.
measure: PsA MDA rate
time frame: 30 months
description: The proportion of patients achieving sustained MDA (from 12 to 24 months)
measure: PsA sustained MDA and atherosclerosis and arterial stiffness
time frame: 30 month
description: Changes in IMT and arterial stiffness over a period of 24 months as evaluated by IMT, PWV and AIx between patients who can achieve sustained MDA and those who cannot achieve sustained MDA.
measure: PsA atherosclerosis and arterial stiffness
time frame: 30 months
description: Correlations between the changes in IMT, PWV, and AIX and the changes in markers of disease activity
arm group label: PsA MDA
arm group type: Other
intervention type: Other
intervention name: PsA MDA
arm group label: PsA MDA
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Chinese University of Hong Kong
investigator full name: Lai-Shan Tam
investigator title: Professor
mesh term: Arthritis
mesh term: Arthritis, Psoriatic
mesh term: Atherosclerosis