<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/NCT04417114</url>
  </required_header>
  <id_info>
    <org_study_id>BWH TBD</org_study_id>
    <nct_id>NCT04417114</nct_id>
  </id_info>
  <brief_title>SystemIc iNflammation and Microvascular diSease PreventIon in psoRiatic diseasE</brief_title>
  <acronym>INSPIRE</acronym>
  <official_title>SystemIc iNflammation and Microvascular diSease PreventIon in psoRiatic diseasE</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Brigham and Women's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Cleveland Clinic</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Brigham and Women's Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a single-label open-arm mechanistic clinical study recruiting patients with psoriasis&#xD;
      or psoriatic arthritis with elevated cardiovascular risk. Subjects enrolled in this study&#xD;
      will receive statin treatment with rosuvastatin. The statin treatment in this study will be&#xD;
      used as an intervention with widely known pleiotropic CV risk reduction effects, including&#xD;
      anti-inflammatory reduction. Subjects will be studied before statin therapy and followed for&#xD;
      48 weeks on treatment. The primary outcome will be change in the coronary flow reserve (CFR)&#xD;
      as measured by cardiac PET. Overall, this study will examine the impact of statin therapy on&#xD;
      changes in CFR as a reflection of impaired coronary vasoreactivity and a manifestation of&#xD;
      myocardial ischemia, which may precede clinical CV events (and visible changes in plaque&#xD;
      morphology) in high-risk patients with psoriatic disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary objective of this study is to investigate the impact of maximally tolerated&#xD;
      statin (MTS) therapy on coronary flow reserve (CFR), reflecting coronary vasoreactivity and&#xD;
      myocardial tissue perfusion. Impaired CFR is a manifestation of myocardial ischemia which may&#xD;
      precede clinical CV events (and visible changes in plaque morphology) in high-risk patients&#xD;
      with psoriatic disease. From previous studies, it is known that traditional risk factors&#xD;
      underestimate cardiovascular risk in psoriatic disease. The central hypothesis of this study,&#xD;
      is that MTS therapy - which has known pleiotropic CV risk reduction effects, including&#xD;
      anti-inflammatory properties -- will quantitatively improve myocardial blood flow and CFR as&#xD;
      measured by positron emission tomography (PET) over one year and reduce atherosclerotic&#xD;
      burden, in patients with moderate-severe psoriasis or psoriatic arthritis. In so doing,&#xD;
      improvement in coronary vasoreactivity, endothelial function, and tissue perfusion may have&#xD;
      beneficial effects on myocardial mechanics, left ventricular deformation and function and,&#xD;
      ultimately, symptoms and prognosis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    The study was not funded.&#xD;
  </why_stopped>
  <start_date type="Anticipated">April 1, 2021</start_date>
  <completion_date type="Anticipated">March 31, 2025</completion_date>
  <primary_completion_date type="Anticipated">March 31, 2025</primary_completion_date>
  <phase>Phase 4</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>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Coronary Flow Reserve (CFR)</measure>
    <time_frame>Baseline and 12 months</time_frame>
    <description>CFR will be measured by cardiac PET at baseline prior to initiating treatment and following 12 months of statin therapy.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in the total coronary plaque burden measured by cardiac CT angiography (CCTA)</measure>
    <time_frame>Baseline and 12 months</time_frame>
    <description>Total coronary plaque burden will be assess by CCTA at baseline and following 12 months of statin therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in change in LV peak global longitudinal strain (GLS) (systolic function), measured by transthoracic echocardiogram (TTE)</measure>
    <time_frame>Baseline and 12 months</time_frame>
    <description>GLS will be measured by TTE at baseline and following 12 months of statin therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in tissue Doppler mitral annular early diastolic relaxation velocity (E') (diastolic function), measured by transthoracic echocardiogram (TTE)</measure>
    <time_frame>Baseline and 12 months</time_frame>
    <description>E' will be measured by TTE at baseline and following 12 months of statin therapy</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Psoriasis</condition>
  <condition>Psoriatic Arthritis</condition>
  <condition>Cardiovascular Risk Factor</condition>
  <arm_group>
    <arm_group_label>Single-Arm Open label</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This is a single-arm open label mechanistic clinical trial. Subjects will be treated with rosuvastatin at a dose of 20mg/day and uptitrated as tolerated to a dose of 40mg/day.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rosuvastatin</intervention_name>
    <description>Statin</description>
    <arm_group_label>Single-Arm Open label</arm_group_label>
    <other_name>Crestor</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt; 40 years of age&#xD;
&#xD;
          -  Documented evidence of PsO or PsA by a board-certified dermatologist or&#xD;
             rheumatologist, respectively.&#xD;
&#xD;
          -  Subjects on systemic therapy/phototherapy for PsO or PsA will be required to be on&#xD;
             stable therapy for at least 3 months prior to enrollment&#xD;
&#xD;
        Plus, documented history of at least one of the following:&#xD;
&#xD;
          1. Hypertension&#xD;
&#xD;
          2. Obesity (BMI &gt; 30)&#xD;
&#xD;
          3. Diabetes Mellitus&#xD;
&#xD;
          4. HsCRP &gt; 3 mg/L within 30 days of enrollment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients on statin or PCSK9 inhibitor therapy, or use of statin therapy within the&#xD;
             past year&#xD;
&#xD;
          -  Documented history of other systemic inflammatory diseases, which in the opinion of&#xD;
             the investigator would be inappropriate for enrollment.&#xD;
&#xD;
          -  Prior history of untreated chronic infection (tuberculosis), severe fungal infection,&#xD;
             or known HIV positive, chronic hepatitis B or C infection), prior history of solid&#xD;
             malignancy, myeloproliferative or lymphoproliferative disease within 5 years,&#xD;
             excluding treated non-melanoma skin cancer&#xD;
&#xD;
          -  NYHA class IV heart failure&#xD;
&#xD;
          -  Active liver disease including unexplained, persistent elevations of serum&#xD;
             transaminases or serum transaminase elevation &gt; 3 x the upper limit of normal.&#xD;
&#xD;
          -  Severe renal impairment&#xD;
&#xD;
          -  Pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marcelo Di Carli, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Brigham and Women's Hospital</affiliation>
  </overall_official>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>June 2, 2020</study_first_submitted>
  <study_first_submitted_qc>June 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>July 19, 2021</last_update_submitted>
  <last_update_submitted_qc>July 19, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 23, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Brigham and Women's Hospital</investigator_affiliation>
    <investigator_full_name>Marcelo F. Di Carli, MD, FACC</investigator_full_name>
    <investigator_title>Chief Division of Nuclear Medicine and Molecular Imaging, Executive Director CV Imaging Program, Principal Investigator, Seltzer Family Professor of Radiology and Medicine</investigator_title>
  </responsible_party>
  <keyword>Coronary microvascular function</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Arthritis, Psoriatic</mesh_term>
    <mesh_term>Psoriasis</mesh_term>
    <mesh_term>Inflammation</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rosuvastatin Calcium</mesh_term>
  </intervention_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/NCT04417114
org study id: BWH TBD
nct id: NCT04417114
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This is a single-label open-arm mechanistic clinical study recruiting patients with psoriasis
      or psoriatic arthritis with elevated cardiovascular risk. Subjects enrolled in this study
      will receive statin treatment with rosuvastatin. The statin treatment in this study will be
      used as an intervention with widely known pleiotropic CV risk reduction effects, including
      anti-inflammatory reduction. Subjects will be studied before statin therapy and followed for
      48 weeks on treatment. The primary outcome will be change in the coronary flow reserve (CFR)
      as measured by cardiac PET. Overall, this study will examine the impact of statin therapy on
      changes in CFR as a reflection of impaired coronary vasoreactivity and a manifestation of
      myocardial ischemia, which may precede clinical CV events (and visible changes in plaque
      morphology) in high-risk patients with psoriatic disease.
The primary objective of this study is to investigate the impact of maximally tolerated
      statin (MTS) therapy on coronary flow reserve (CFR), reflecting coronary vasoreactivity and
      myocardial tissue perfusion. Impaired CFR is a manifestation of myocardial ischemia which may
      precede clinical CV events (and visible changes in plaque morphology) in high-risk patients
      with psoriatic disease. From previous studies, it is known that traditional risk factors
      underestimate cardiovascular risk in psoriatic disease. The central hypothesis of this study,
      is that MTS therapy - which has known pleiotropic CV risk reduction effects, including
      anti-inflammatory properties -- will quantitatively improve myocardial blood flow and CFR as
      measured by positron emission tomography (PET) over one year and reduce atherosclerotic
      burden, in patients with moderate-severe psoriasis or psoriatic arthritis. In so doing,
      improvement in coronary vasoreactivity, endothelial function, and tissue perfusion may have
      beneficial effects on myocardial mechanics, left ventricular deformation and function and,
      ultimately, symptoms and prognosis.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Change in Coronary Flow Reserve (CFR)
time frame: Baseline and 12 months
description: CFR will be measured by cardiac PET at baseline prior to initiating treatment and following 12 months of statin therapy.
measure: Change in the total coronary plaque burden measured by cardiac CT angiography (CCTA)
time frame: Baseline and 12 months
description: Total coronary plaque burden will be assess by CCTA at baseline and following 12 months of statin therapy
measure: Change in change in LV peak global longitudinal strain (GLS) (systolic function), measured by transthoracic echocardiogram (TTE)
time frame: Baseline and 12 months
description: GLS will be measured by TTE at baseline and following 12 months of statin therapy
measure: Change in tissue Doppler mitral annular early diastolic relaxation velocity (E') (diastolic function), measured by transthoracic echocardiogram (TTE)
time frame: Baseline and 12 months
description: E' will be measured by TTE at baseline and following 12 months of statin therapy
arm group label: Single-Arm Open label
arm group type: Experimental
description: This is a single-arm open label mechanistic clinical trial. Subjects will be treated with rosuvastatin at a dose of 20mg/day and uptitrated as tolerated to a dose of 40mg/day.
intervention type: Drug
intervention name: Rosuvastatin
description: Statin
arm group label: Single-Arm Open label
other name: Crestor
criteria: 
gender: All
minimum age: 40 Years
maximum age: 80 Years
healthy volunteers: No
last name: Marcelo Di Carli, MD
role: Principal Investigator
affiliation: Brigham and Women's Hospital
responsible party type: Principal Investigator
investigator affiliation: Brigham and Women's Hospital
investigator full name: Marcelo F. Di Carli, MD, FACC
investigator title: Chief Division of Nuclear Medicine and Molecular Imaging, Executive Director CV Imaging Program, Principal Investigator, Seltzer Family Professor of Radiology and Medicine
mesh term: Arthritis, Psoriatic
mesh term: Psoriasis
mesh term: Inflammation
mesh term: Rosuvastatin Calcium
sharing ipd: No