<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/NCT02219646</url>
  </required_header>
  <id_info>
    <org_study_id>EudraCT number 2009-014137-25</org_study_id>
    <nct_id>NCT02219646</nct_id>
  </id_info>
  <brief_title>Diabetes &amp; Vardenafil</brief_title>
  <acronym>DiVa</acronym>
  <official_title>Monitoring of Endothelial Dysfunction During Chronic Administration of Vardenafil in Patients With Type 2 Diabetes Mellitus: A Longitudinal, Randomised, Placebo-controlled, Double Blind, Phase II b, Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Azienda USL Modena</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Azienda USL Modena</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Given the protective effect of nitric oxide (NO) on the endothelium and the results obtained&#xD;
      so far in short-term, continuous treatment with phosphodiesterase-5 (PDE5) inhibitors on&#xD;
      parameters of endothelial function, we hypothesise that chronic treatment with vardenafil can&#xD;
      prevent or delay the deterioration of systemic endothelial function in patients with type 2&#xD;
      diabetes mellitus. The favourable effect of PDE5 inhibitors on sexual function in these&#xD;
      patients has been convincingly demonstrated in the past. Here we hypothesise that vardenafil&#xD;
      treatment can have beneficial effects on the vascular physiology in other body districts,&#xD;
      possibly preventing the development of microangiopathy and atherosclerotic cardiovascular&#xD;
      disease in these patients.&#xD;
&#xD;
      The main goal of this study is therefore to monitor the endothelial dysfunction during&#xD;
      continuous treatment with vardenafil for 6 months; object of the study will be endothelin 1&#xD;
      and other known parameters of endothelial damage in newly diagnosed patients with type 2&#xD;
      diabetes mellitus.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Phosphodiesterase-5 (PDE5) inhibitors are currently used in the therapy of erectile&#xD;
      dysfunction (ED), which is considered to be an early symptom of cardiovascular disease (CD).&#xD;
      Impairment of endothelial function is the early lesion preceding atherosclerosis and is&#xD;
      common to ED, CD and vascular complications of diabetes mellitus (DM). Continuous&#xD;
      administration of the PDE5 inhibitors tadalafil or sildenafil for four weeks in men with&#xD;
      increased cardiovascular risk or type 2 DM has been shown to improve endothelial function&#xD;
      measured by flow-mediated dilation and reduction of inflammatory markers. The goal of this&#xD;
      study is to investigate whether chronic, long-term treatment with vardenafil improves and/or&#xD;
      prevents deterioration of systemic endothelial function in patients with type 2 DM. Study&#xD;
      design: longitudinal, double-blind, randomised, placebo-controlled interventional study.&#xD;
      Patients: 106 male patients (n determined by power analysis) with type 2 DM diagnosed and&#xD;
      classified according to the guidelines of the European Association for the Study of Diabetes.&#xD;
      Beside the antidiabetic treatment, patients will be randomly assigned to receive either&#xD;
      placebo or vardenafil, 10 mg p.o. two times a day for 24 weeks. Exclusion criteria: all&#xD;
      contraindications to treatment with PDE5 inhibitors. Age range: 40-60 years. Sample size&#xD;
      determined by power analysis assuming variations of the primary end point of ± 10% from&#xD;
      baseline at 0.05 α level with a power of 80%, a two-sided test and a dropout rate of 15%.&#xD;
      Primary end point: serum endothelin 1 levels (decreased/not increased in the verum group vs.&#xD;
      not decrease/increased in the placebo group). Other parameters and measurements: Complete&#xD;
      clinical workup, weight, height, waist-hip ratio, serum lipids and glucose, hemoglobin&#xD;
      glycated (HbA1c), micro- and macroalbuminuria, homocysteine, high reactive C-protein (hsCRP),&#xD;
      interleukin-6 (IL-6), Tumor necrosis factor (TNF)α, fibrinogen, adiponectin, testosterone,&#xD;
      sex hormone-binding globulin (SHBG) and estradiol. All parameters measured at baseline, 4&#xD;
      weeks, 12 weeks and 24 weeks on medication as well as 4 and 24 weeks after discontinuation of&#xD;
      the study drug. Study duration: two years. Statistics: descriptive statistics, ANCOVA and&#xD;
      multiple regression analysis or non-parametric tests as appropriate by STATA. Ethics: The&#xD;
      trial will be registered. Ethics committee approval and patient informed consent will be&#xD;
      obtained. Expected outcome and objective: Monitoring of endothelial function deterioration in&#xD;
      type 2 DM during chronic administration of Vardenafil. Possibility for a long term-follow up&#xD;
      study. Publication in a high impact factor journal.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>March 2010</start_date>
  <completion_date type="Actual">February 2014</completion_date>
  <primary_completion_date type="Actual">February 2013</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Endothelin-1</measure>
    <time_frame>&quot;6 months&quot;</time_frame>
    <description>change in serum endothelin 1 concentration</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Flow Mediated Dilation</measure>
    <time_frame>&quot;baseline&quot;</time_frame>
    <description>Change of flow mediated dilation evaluated by ultrasonography at brachial artery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Flow Mediated dilation (FMD)</measure>
    <time_frame>&quot;6 months&quot;</time_frame>
    <description>Change of FMD levels</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Flow Mediated Dilation</measure>
    <time_frame>&quot;One year&quot;</time_frame>
    <description>Change of FMD levels</description>
  </secondary_outcome>
  <other_outcome>
    <measure>carotid Intima Media Thickness</measure>
    <time_frame>&quot;baseline&quot;</time_frame>
    <description>Change of ultrasonographic evaluation of intima-media thickness at both right and left carotid arteries</description>
  </other_outcome>
  <other_outcome>
    <measure>carotid Intima Media Thickness (IMT)</measure>
    <time_frame>&quot;6 months&quot;</time_frame>
    <description>Change in IMT levels</description>
  </other_outcome>
  <other_outcome>
    <measure>carotid Intima Media Thickness</measure>
    <time_frame>&quot;One year&quot;</time_frame>
    <description>change in IMT levels</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">54</enrollment>
  <condition>Type 2 Diabetes Mellitus (T2DM)</condition>
  <condition>Endothelial Dysfunction</condition>
  <condition>Erectile Dysfunction</condition>
  <arm_group>
    <arm_group_label>Vardenafil</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The study protocol consists of a Screening/Enrolment Phase lasting up to 4 weeks, a Treatment Phase of 24 weeks, and Follow-up/Observation Treatment-free Phase of 24 weeks after the Treatment Phase. During treatment phase, patients enrolled in the Study Group were treated with vardenafil 10 mg twice/daily.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The study protocol consists of a Screening/Enrolment Phase lasting up to 4 weeks, a Treatment Phase of 24 weeks, and Follow-up/Observation Treatment-free Phase of 24 weeks after the Treatment Phase. During treatment phase, patients enrolled in the Control Group were treated with tablets twice/daily identical to the Study Group, but containing placebo.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vardenafil</intervention_name>
    <description>Vardenafil 10 mg twice daily for six months</description>
    <arm_group_label>Vardenafil</arm_group_label>
    <other_name>Levitra</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo two tablets daily for 6 months</description>
    <arm_group_label>Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male gender&#xD;
&#xD;
          -  Signed written Consent Form&#xD;
&#xD;
          -  Type 2 diabetes mellitus diagnosed within 5 years before enrolment in the study&#xD;
&#xD;
          -  Body Mass Index (BMI) &lt; 35&#xD;
&#xD;
          -  ED (severe, moderate or light according to the International Index of Erectile&#xD;
             Function - erectile function domain score &lt; 26 (Rosen et al. 1997))&#xD;
&#xD;
          -  Age range: 40-65 years.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Systemic diseases except type 2 diabetes mellitus&#xD;
&#xD;
          -  Absence of ED&#xD;
&#xD;
          -  Psychiatric disorders&#xD;
&#xD;
          -  All contraindications to treatment with PDE5 inhibitors, such as retinitis pigmentosa,&#xD;
             non-arteritic anterior ischaemic optic neuropathy, history of coronary artery disease,&#xD;
             recent myocardial infarction, unstable angina, systemic arterial hypotension,&#xD;
             nitric-oxide donors therapy, severe hepatic and renal failure.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Manuela Simoni, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Azienda USL Modena</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Unit of Endocrinology Azienda USL</name>
      <address>
        <city>Modena</city>
        <zip>41126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>August 2014</verification_date>
  <study_first_submitted>July 24, 2014</study_first_submitted>
  <study_first_submitted_qc>August 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 19, 2014</study_first_posted>
  <last_update_submitted>August 18, 2014</last_update_submitted>
  <last_update_submitted_qc>August 18, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 19, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Azienda USL Modena</investigator_affiliation>
    <investigator_full_name>Manuela Simoni</investigator_full_name>
    <investigator_title>Ordinary Professor</investigator_title>
  </responsible_party>
  <keyword>T2DM</keyword>
  <keyword>ED</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Erectile Dysfunction</mesh_term>
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vardenafil Dihydrochloride</mesh_term>
  </intervention_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/NCT02219646
org study id: EudraCT number 2009-014137-25
nct id: NCT02219646
lead sponsor: 
has dmc: Yes
Given the protective effect of nitric oxide (NO) on the endothelium and the results obtained
      so far in short-term, continuous treatment with phosphodiesterase-5 (PDE5) inhibitors on
      parameters of endothelial function, we hypothesise that chronic treatment with vardenafil can
      prevent or delay the deterioration of systemic endothelial function in patients with type 2
      diabetes mellitus. The favourable effect of PDE5 inhibitors on sexual function in these
      patients has been convincingly demonstrated in the past. Here we hypothesise that vardenafil
      treatment can have beneficial effects on the vascular physiology in other body districts,
      possibly preventing the development of microangiopathy and atherosclerotic cardiovascular
      disease in these patients.

      The main goal of this study is therefore to monitor the endothelial dysfunction during
      continuous treatment with vardenafil for 6 months; object of the study will be endothelin 1
      and other known parameters of endothelial damage in newly diagnosed patients with type 2
      diabetes mellitus.
Phosphodiesterase-5 (PDE5) inhibitors are currently used in the therapy of erectile
      dysfunction (ED), which is considered to be an early symptom of cardiovascular disease (CD).
      Impairment of endothelial function is the early lesion preceding atherosclerosis and is
      common to ED, CD and vascular complications of diabetes mellitus (DM). Continuous
      administration of the PDE5 inhibitors tadalafil or sildenafil for four weeks in men with
      increased cardiovascular risk or type 2 DM has been shown to improve endothelial function
      measured by flow-mediated dilation and reduction of inflammatory markers. The goal of this
      study is to investigate whether chronic, long-term treatment with vardenafil improves and/or
      prevents deterioration of systemic endothelial function in patients with type 2 DM. Study
      design: longitudinal, double-blind, randomised, placebo-controlled interventional study.
      Patients: 106 male patients (n determined by power analysis) with type 2 DM diagnosed and
      classified according to the guidelines of the European Association for the Study of Diabetes.
      Beside the antidiabetic treatment, patients will be randomly assigned to receive either
      placebo or vardenafil, 10 mg p.o. two times a day for 24 weeks. Exclusion criteria: all
      contraindications to treatment with PDE5 inhibitors. Age range: 40-60 years. Sample size
      determined by power analysis assuming variations of the primary end point of ± 10% from
      baseline at 0.05 α level with a power of 80%, a two-sided test and a dropout rate of 15%.
      Primary end point: serum endothelin 1 levels (decreased/not increased in the verum group vs.
      not decrease/increased in the placebo group). Other parameters and measurements: Complete
      clinical workup, weight, height, waist-hip ratio, serum lipids and glucose, hemoglobin
      glycated (HbA1c), micro- and macroalbuminuria, homocysteine, high reactive C-protein (hsCRP),
      interleukin-6 (IL-6), Tumor necrosis factor (TNF)α, fibrinogen, adiponectin, testosterone,
      sex hormone-binding globulin (SHBG) and estradiol. All parameters measured at baseline, 4
      weeks, 12 weeks and 24 weeks on medication as well as 4 and 24 weeks after discontinuation of
      the study drug. Study duration: two years. Statistics: descriptive statistics, ANCOVA and
      multiple regression analysis or non-parametric tests as appropriate by STATA. Ethics: The
      trial will be registered. Ethics committee approval and patient informed consent will be
      obtained. Expected outcome and objective: Monitoring of endothelial function deterioration in
      type 2 DM during chronic administration of Vardenafil. Possibility for a long term-follow up
      study. Publication in a high impact factor journal.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Endothelin-1
time frame: "6 months"
description: change in serum endothelin 1 concentration
measure: Flow Mediated Dilation
time frame: "baseline"
description: Change of flow mediated dilation evaluated by ultrasonography at brachial artery
measure: Flow Mediated dilation (FMD)
time frame: "6 months"
description: Change of FMD levels
measure: Flow Mediated Dilation
time frame: "One year"
description: Change of FMD levels
measure: carotid Intima Media Thickness
time frame: "baseline"
description: Change of ultrasonographic evaluation of intima-media thickness at both right and left carotid arteries
measure: carotid Intima Media Thickness (IMT)
time frame: "6 months"
description: Change in IMT levels
measure: carotid Intima Media Thickness
time frame: "One year"
description: change in IMT levels
arm group label: Vardenafil
arm group type: Experimental
description: The study protocol consists of a Screening/Enrolment Phase lasting up to 4 weeks, a Treatment Phase of 24 weeks, and Follow-up/Observation Treatment-free Phase of 24 weeks after the Treatment Phase. During treatment phase, patients enrolled in the Study Group were treated with vardenafil 10 mg twice/daily.
arm group label: Control
arm group type: Placebo Comparator
description: The study protocol consists of a Screening/Enrolment Phase lasting up to 4 weeks, a Treatment Phase of 24 weeks, and Follow-up/Observation Treatment-free Phase of 24 weeks after the Treatment Phase. During treatment phase, patients enrolled in the Control Group were treated with tablets twice/daily identical to the Study Group, but containing placebo.
intervention type: Drug
intervention name: Vardenafil
description: Vardenafil 10 mg twice daily for six months
arm group label: Vardenafil
other name: Levitra
intervention type: Drug
intervention name: Placebo
description: Placebo two tablets daily for 6 months
arm group label: Control
criteria: 
gender: Male
minimum age: 40 Years
maximum age: 65 Years
healthy volunteers: No
last name: Manuela Simoni, MD, PhD
role: Principal Investigator
affiliation: Azienda USL Modena
facility: 
country: Italy
responsible party type: Principal Investigator
investigator affiliation: Azienda USL Modena
investigator full name: Manuela Simoni
investigator title: Ordinary Professor
mesh term: Erectile Dysfunction
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Vardenafil Dihydrochloride