<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/NCT04469829</url>
  </required_header>
  <id_info>
    <org_study_id>Gisondi5</org_study_id>
    <nct_id>NCT04469829</nct_id>
  </id_info>
  <brief_title>Methotrexate Versus Secukinumab Safety in Psoriasis Patients With Metabolic Syndrome</brief_title>
  <official_title>Methotrexate Versus Secukinumab Safety in Psoriasis Patients With Metabolic Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universita di Verona</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Universita di Verona</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      A prospective, controlled, open trial in psoriasis patients with metabolic syndrome,&#xD;
      candidate to methotrexate or secukinumab was conducted between January 2019 and May 2020. The&#xD;
      primary end point of the study was investigating any variations in waist circumference, body&#xD;
      mass index (BMI), blood pressure, fasting glucose, total cholesterol, low density lipoprotein&#xD;
      (LDL)-cholesterol, high density lipoprotein (HDL)-cholesterol, triglycerides, aspartate&#xD;
      aminotransferase (AST), alanine aminotransferase (ALT), creatinine levels between baseline&#xD;
      and month-6 and 12 of follow-up.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A prospective, non-randomized controlled open trial in psoriasis patients with metabolic&#xD;
      syndrome was conducted between January 2019 and May 2020. Inclusion criteria were age ≥ 18&#xD;
      years, being affected by moderate to severe chronic plaque psoriasis and concomitant&#xD;
      metabolic syndrome and being candidate to systemic treatment with methotrexate or secukinumab&#xD;
      according to the Italian guideline for psoriasis. Psoriasis was diagnosed on clinical base,&#xD;
      and it was classified as moderate to severe if PASI ≥ 10, Investigator Global Assessment&#xD;
      (IGA) score≥ 3 and/or Dermatology Life Quality Index ≥ 10%. Metabolic syndrome was diagnosed&#xD;
      according to criteria of the National Cholesterol Education Programme Adult Treatment Panel&#xD;
      III (NCEP ATP III) and The American Heart Association and the National Heart, Lung, and Blood&#xD;
      Institute (AHA/NHLB).3 In particular, metabolic syndrome was confirmed in presence of at&#xD;
      least three of the following components: abdominal obesity (waist circumference ≥ 102 cm for&#xD;
      men or ≥ 88 cm for women), triglycerides ≥ 150 mg/dL, HDL cholesterol ≤ 40 mg/dL for men or&#xD;
      50 mg/dL for women, systolic/diastolic blood pressure ≥ 130/85 mmHg or receiving drug&#xD;
      treatment, and fasting plasma glucose ≥ 100 mg/dL. Exclusion criteria were being affected by&#xD;
      psoriatic arthritis, pregnancy, breast feeding, having initiated a systemic treatment for&#xD;
      psoriasis in the previous 3 months and having a clinical condition that could affect the&#xD;
      metabolic parameters other than metabolic syndrome. After having signed the informed consent&#xD;
      for the participation in the study, eligible patients were consecutively assigned in a 1:1&#xD;
      ratio to secukinumab (standard dose) or methotrexate 15 mg/week by subcutaneous&#xD;
      administration and folic acid supplementation 5 mg given 24 hours after methotrexate. The&#xD;
      primary endpoint was investigating any variation in waist circumference, body mass index&#xD;
      (BMI), blood pressure, fasting glucose, total cholesterol, low density lipoprotein&#xD;
      (LDL)-cholesterol, high density lipoprotein (HDL)-cholesterol, triglycerides, aspartate&#xD;
      aminotransferase (AST), alanine aminotransferase (ALT), creatinine levels at month-6. Any&#xD;
      other adverse events related to the treatments and the proportion of patients who&#xD;
      discontinued the treatment because of adverse reactions were also reported. The secondary&#xD;
      endpoints were assessing the PASI 75 and PASI 90 proportion of responders in the two groups&#xD;
      at 6 and 12 months follow-up. Clinical and laboratory data were evaluated at the baseline and&#xD;
      every 3 months up to month 12.&#xD;
&#xD;
      Statistical Methods A descriptive statistic was conducted using proportions for categorical&#xD;
      and mean and standard deviation (SD) for quantitative variables. The categorical variables&#xD;
      were compared between the groups using the chi-squared test, while the quantitative variables&#xD;
      were compared using the Student's T test. Variations in waist circumference, BMI, blood&#xD;
      pressure, fasting glucose, total cholesterol, LDL cholesterol, HDL cholesterol,&#xD;
      triglycerides, AST, ALT, creatinine levels between baseline and month-6 or 12 were assessed&#xD;
      by paired t-test in patient receiving methotrexate or secukinumab, respectively. PASI 75 and&#xD;
      PASI 90 proportion of responders at month -6 or 12 in the two cohorts' were compared by the&#xD;
      chi-squared test. The normal distribution of data was confirmed using the one-sample&#xD;
      Kolmogorov-Smirnov Test. A value of p&lt; 0.05 was considered statistically significant.&#xD;
      Statistical analysis was performed using the STATA (version 13 StataCorp, College Station,&#xD;
      TX, U.S.A.).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">August 1, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2021</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in waist circumference at month 12</measure>
    <time_frame>12 month</time_frame>
    <description>Changes in waist circumference at month 12</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in BMI at month 12</measure>
    <time_frame>12 month</time_frame>
    <description>Changes in BMI at month 12</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in blood pressure at month 12</measure>
    <time_frame>12 month</time_frame>
    <description>Changes in blood pressure at month 12</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in fasting glucose at month 12</measure>
    <time_frame>12 month</time_frame>
    <description>Changes in fasting glucose at month 12</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in total cholesterol at month 12</measure>
    <time_frame>12 month</time_frame>
    <description>Changes in total cholesterol at month 12</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in LDL cholesterol at month 12</measure>
    <time_frame>12 month</time_frame>
    <description>Changes in LDL cholesterol at month 12</description>
  </primary_outcome>
  <primary_outcome>
    <measure>changes in (HDL)-cholesterol at month 12</measure>
    <time_frame>12 month</time_frame>
    <description>changes in (HDL)-cholesterol at month 12</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in triglycerides at month 12</measure>
    <time_frame>12 month</time_frame>
    <description>Changes in triglycerides at month 12</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in AST at month 12</measure>
    <time_frame>month 12</time_frame>
    <description>Changes in AST at month 12</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in ALT at month 12</measure>
    <time_frame>month 12</time_frame>
    <description>Changes in ALT at month 12</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PASI75 and PASI90</measure>
    <time_frame>6 and 12 months</time_frame>
    <description>assessing the PASI 75 and PASI 90 proportion of responders in the two groups at 6 and 12 months follow-up</description>
  </secondary_outcome>
  <other_outcome>
    <measure>adverse reactions</measure>
    <time_frame>6 and 12 months</time_frame>
    <description>other adverse events related to the treatments and the proportion of patients who discontinued the treatment because of adverse reactions</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">70</enrollment>
  <condition>Psoriasis</condition>
  <condition>Metabolic Syndrome</condition>
  <arm_group>
    <arm_group_label>secukinumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>patients with psoriasis and metabolic syndrome candidate for treatment with secukinumab standard doses</description>
  </arm_group>
  <arm_group>
    <arm_group_label>methotrexate</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>patients with psoriasis and metabolic syndrome candidate for treatment with methotrexate dosed 15 mg/week</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Secukinumab</intervention_name>
    <description>standard doses of secukinumab for psoriasis</description>
    <arm_group_label>secukinumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methotrexate</intervention_name>
    <description>Methotrexate 15 mg/week</description>
    <arm_group_label>methotrexate</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  age ≥ 18 years&#xD;
&#xD;
          -  being affected by moderate to severe chronic plaque psoriasis and concomitant&#xD;
             metabolic syndrome&#xD;
&#xD;
          -  being candidate to systemic treatment with methotrexate or secukinumab according to&#xD;
             the Italian guideline for psoriasis&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  being affected by psoriatic arthritis, pregnancy, breast feeding,&#xD;
&#xD;
          -  having initiated a systemic treatment for psoriasis in the previous 3 months and&#xD;
             having a clinical condition that could affect the metabolic parameters other than&#xD;
             metabolic syndrome.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Paolo Gisondi, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Universita di Verona</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Paolo Gisondi, MD</last_name>
    <phone>045 8122546</phone>
    <phone_ext>0039</phone_ext>
    <email>paolo.gisondi@univr.it</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Verona</name>
      <address>
        <city>Verona</city>
        <zip>37126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 2, 2020</study_first_submitted>
  <study_first_submitted_qc>July 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 14, 2020</study_first_posted>
  <last_update_submitted>July 8, 2020</last_update_submitted>
  <last_update_submitted_qc>July 8, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 14, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Universita di Verona</investigator_affiliation>
    <investigator_full_name>Paolo Gisondi</investigator_full_name>
    <investigator_title>Prof</investigator_title>
  </responsible_party>
  <keyword>psoriasis</keyword>
  <keyword>methotrexate</keyword>
  <keyword>secukinumab</keyword>
  <keyword>metabolic syndrome</keyword>
  <keyword>safety</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Psoriasis</mesh_term>
    <mesh_term>Metabolic Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Methotrexate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04469829
org study id: Gisondi5
nct id: NCT04469829
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
A prospective, controlled, open trial in psoriasis patients with metabolic syndrome,
      candidate to methotrexate or secukinumab was conducted between January 2019 and May 2020. The
      primary end point of the study was investigating any variations in waist circumference, body
      mass index (BMI), blood pressure, fasting glucose, total cholesterol, low density lipoprotein
      (LDL)-cholesterol, high density lipoprotein (HDL)-cholesterol, triglycerides, aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), creatinine levels between baseline
      and month-6 and 12 of follow-up.
A prospective, non-randomized controlled open trial in psoriasis patients with metabolic
      syndrome was conducted between January 2019 and May 2020. Inclusion criteria were age ≥ 18
      years, being affected by moderate to severe chronic plaque psoriasis and concomitant
      metabolic syndrome and being candidate to systemic treatment with methotrexate or secukinumab
      according to the Italian guideline for psoriasis. Psoriasis was diagnosed on clinical base,
      and it was classified as moderate to severe if PASI ≥ 10, Investigator Global Assessment
      (IGA) score≥ 3 and/or Dermatology Life Quality Index ≥ 10%. Metabolic syndrome was diagnosed
      according to criteria of the National Cholesterol Education Programme Adult Treatment Panel
      III (NCEP ATP III) and The American Heart Association and the National Heart, Lung, and Blood
      Institute (AHA/NHLB).3 In particular, metabolic syndrome was confirmed in presence of at
      least three of the following components: abdominal obesity (waist circumference ≥ 102 cm for
      men or ≥ 88 cm for women), triglycerides ≥ 150 mg/dL, HDL cholesterol ≤ 40 mg/dL for men or
      50 mg/dL for women, systolic/diastolic blood pressure ≥ 130/85 mmHg or receiving drug
      treatment, and fasting plasma glucose ≥ 100 mg/dL. Exclusion criteria were being affected by
      psoriatic arthritis, pregnancy, breast feeding, having initiated a systemic treatment for
      psoriasis in the previous 3 months and having a clinical condition that could affect the
      metabolic parameters other than metabolic syndrome. After having signed the informed consent
      for the participation in the study, eligible patients were consecutively assigned in a 1:1
      ratio to secukinumab (standard dose) or methotrexate 15 mg/week by subcutaneous
      administration and folic acid supplementation 5 mg given 24 hours after methotrexate. The
      primary endpoint was investigating any variation in waist circumference, body mass index
      (BMI), blood pressure, fasting glucose, total cholesterol, low density lipoprotein
      (LDL)-cholesterol, high density lipoprotein (HDL)-cholesterol, triglycerides, aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), creatinine levels at month-6. Any
      other adverse events related to the treatments and the proportion of patients who
      discontinued the treatment because of adverse reactions were also reported. The secondary
      endpoints were assessing the PASI 75 and PASI 90 proportion of responders in the two groups
      at 6 and 12 months follow-up. Clinical and laboratory data were evaluated at the baseline and
      every 3 months up to month 12.

      Statistical Methods A descriptive statistic was conducted using proportions for categorical
      and mean and standard deviation (SD) for quantitative variables. The categorical variables
      were compared between the groups using the chi-squared test, while the quantitative variables
      were compared using the Student's T test. Variations in waist circumference, BMI, blood
      pressure, fasting glucose, total cholesterol, LDL cholesterol, HDL cholesterol,
      triglycerides, AST, ALT, creatinine levels between baseline and month-6 or 12 were assessed
      by paired t-test in patient receiving methotrexate or secukinumab, respectively. PASI 75 and
      PASI 90 proportion of responders at month -6 or 12 in the two cohorts' were compared by the
      chi-squared test. The normal distribution of data was confirmed using the one-sample
      Kolmogorov-Smirnov Test. A value of p< 0.05 was considered statistically significant.
      Statistical analysis was performed using the STATA (version 13 StataCorp, College Station,
      TX, U.S.A.).
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Changes in waist circumference at month 12
time frame: 12 month
description: Changes in waist circumference at month 12
measure: Changes in BMI at month 12
time frame: 12 month
description: Changes in BMI at month 12
measure: Changes in blood pressure at month 12
time frame: 12 month
description: Changes in blood pressure at month 12
measure: Changes in fasting glucose at month 12
time frame: 12 month
description: Changes in fasting glucose at month 12
measure: Changes in total cholesterol at month 12
time frame: 12 month
description: Changes in total cholesterol at month 12
measure: Changes in LDL cholesterol at month 12
time frame: 12 month
description: Changes in LDL cholesterol at month 12
measure: changes in (HDL)-cholesterol at month 12
time frame: 12 month
description: changes in (HDL)-cholesterol at month 12
measure: Changes in triglycerides at month 12
time frame: 12 month
description: Changes in triglycerides at month 12
measure: Changes in AST at month 12
time frame: month 12
description: Changes in AST at month 12
measure: Changes in ALT at month 12
time frame: month 12
description: Changes in ALT at month 12
measure: PASI75 and PASI90
time frame: 6 and 12 months
description: assessing the PASI 75 and PASI 90 proportion of responders in the two groups at 6 and 12 months follow-up
measure: adverse reactions
time frame: 6 and 12 months
description: other adverse events related to the treatments and the proportion of patients who discontinued the treatment because of adverse reactions
arm group label: secukinumab
arm group type: Experimental
description: patients with psoriasis and metabolic syndrome candidate for treatment with secukinumab standard doses
arm group label: methotrexate
arm group type: Active Comparator
description: patients with psoriasis and metabolic syndrome candidate for treatment with methotrexate dosed 15 mg/week
intervention type: Drug
intervention name: Secukinumab
description: standard doses of secukinumab for psoriasis
arm group label: secukinumab
intervention type: Drug
intervention name: Methotrexate
description: Methotrexate 15 mg/week
arm group label: methotrexate
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Paolo Gisondi, MD
role: Principal Investigator
affiliation: Universita di Verona
last name: Paolo Gisondi, MD
phone: 045 8122546
phone ext: 0039
email: paolo.gisondi@univr.it
facility: 
country: Italy
responsible party type: Principal Investigator
investigator affiliation: Universita di Verona
investigator full name: Paolo Gisondi
investigator title: Prof
mesh term: Psoriasis
mesh term: Metabolic Syndrome
mesh term: Syndrome
mesh term: Methotrexate
sharing ipd: Undecided