<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/NCT02252367</url>
  </required_header>
  <id_info>
    <org_study_id>ANDRO-AOUC-2014-01</org_study_id>
    <nct_id>NCT02252367</nct_id>
  </id_info>
  <brief_title>Effect of 12 Weeks Treatment With Tadalafil vs Placebo on Lower Urinary Tract Symptoms</brief_title>
  <official_title>Double-blind, Placebo-controlled Study on Men With Lower Urinary Tract Symptoms to Assess Changes in Pressure Flow Study and in Molecular Profile of Prostatic Tissue After 12 Weeks Treatment With Tadalafil.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Florence</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Eli Lilly and Company</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Florence</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      At present time several preclinical and clinical study have demonstrated the safety and&#xD;
      efficacy of PDE5 (phosphodiesterase type 5)-inhibitors for LUTS/BPH (lower urinary tract&#xD;
      symptoms/benign prostatic hyperplasia) patients with or without erectile dysfunction.&#xD;
      However, the link between clinical outcomes (symptoms scores), functional activity&#xD;
      (urodynamic findings) and molecular pathways, in particular regarding inflammatory pattern&#xD;
      (molecular analyses), has not been previously investigated.&#xD;
&#xD;
      Aim of present study is to assess, for the first time in literature, changes in pressure flow&#xD;
      study (PFS) and changes in molecular profile of prostatic tissue (inflammatory and tissue&#xD;
      remodeling markers) in men treated for 12 weeks with tadalafil 5 mg compared with placebo and&#xD;
      to correlate these data with changes in symptoms scores (IPSS, International Prostatic&#xD;
      Symptoms Score) in men with LUTS secondary to BPH refractory to alpha blockers.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 2015</start_date>
  <completion_date type="Actual">June 2020</completion_date>
  <primary_completion_date type="Actual">January 2019</primary_completion_date>
  <phase>Phase 4</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>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Improvement of LUTS/BPH symptoms</measure>
    <time_frame>12 weeks</time_frame>
    <description>BPH-associated inflammatory symptoms will be assessed by using the National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI). BPH-associated LUTS will be assessed by using International Prostate Symptom Score (IPSS).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Improvement of pressure flow study (PFS) parameters</measure>
    <time_frame>12 weeks</time_frame>
    <description>Maximum flow rate (Qmax), average flow rate (Qave), voided volume (Vcomp), post void residual volume (PVR) will be evaluated. An abdominal ultrasound immediately after voiding for uroflowmetry will be performed in order to determine the PVR.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volumetric change of the prostate</measure>
    <time_frame>12 weeks</time_frame>
    <description>Prostate volume as assessed by transrectal ultrasound</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in prostate inhomogeneity and in the number of prostatic macrocalcifications</measure>
    <time_frame>12 weeks</time_frame>
    <description>BPH-associated prostate inhomogeneity and presence of micro-calcifications will be assessed by using male genital tract male genital tract colour-Doppler ultrasonography.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Variation in genic expression of prostatic inflammation markers</measure>
    <time_frame>12 weeks</time_frame>
    <description>BPH-associated prostate inflammation, fibrosis, and hypoxia will be measured by immunohistochemical and quantitative RT-PCR (qRT-PCR) analyses of inflammatory-, fibrosis- and hypoxia-related markers.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Variation in serum inflammation markers CRP (C-reactive protein) and ESR (Erythrocyte Sedimentation Rate)</measure>
    <time_frame>12 weeks</time_frame>
    <description>CRP measured on serum and ESR measured on blood drawn at baseline and after 12 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement in metabolic profile</measure>
    <time_frame>12 weeks</time_frame>
    <description>Metabolic parameters will be evaluated (glycaemia, insulinemia, total cholesterol, HDL, triglycerides, HbA1c, mean arterial pressure, waist circumference, body mass index)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Variation in seminal plasma IL-8 (interleukin-8) levels</measure>
    <time_frame>12 weeks</time_frame>
    <description>Seminal IL-8, a chemokine involved in male genital tract infection/inflammation, will be evaluated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement in erectile function</measure>
    <time_frame>12 weeks</time_frame>
    <description>Erectile function will be assessed by using the International Index of Erectile Function-5 (IIEF-5) score.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">86</enrollment>
  <condition>Prostatic Hyperplasia</condition>
  <condition>Lower Urinary Tract Symptoms</condition>
  <arm_group>
    <arm_group_label>Tadalafil</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>43 male subjects affected by BPH (benign prostatic hyperplasia) planned for simple prostatectomy will be randomized to tadalafil 5 mg - 1 film-coated tablet orally once daily for 12 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>43 male subjects affected by BPH (benign prostatic hyperplasia) planned for simple prostatectomy will be randomized to placebo.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tadalafil</intervention_name>
    <description>Tadalafil 5 mg once daily for 12 weeks.</description>
    <arm_group_label>Tadalafil</arm_group_label>
    <other_name>Cialis</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo tablet once daily for 12 weeks.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  adult male subjects planned to undergo simple prostatectomy (TURP, Transurethral&#xD;
             resection of the prostate, or open prostatectomy) for benign prostatic hyperplasia;&#xD;
&#xD;
          -  treatment with alpha-blockers (Tamsulosin 0.4 mg/die)&#xD;
&#xD;
          -  being capable of giving informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  participation in another clinical study;&#xD;
&#xD;
          -  known or suspected presence of prostatic cancer or PSA (prostate specific antigen)&#xD;
             value &gt;10 ng/mL;&#xD;
&#xD;
          -  suspected lack of the participant's compliance;&#xD;
&#xD;
          -  known severe allergies or hypersensitivity to the study drug (active substance or&#xD;
             excipients of the formulation);&#xD;
&#xD;
          -  nown neurogenic bladder (i.e. Parkinson's disease);&#xD;
&#xD;
          -  suspected or proven urinary infections;&#xD;
&#xD;
          -  presence of bladder stone.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mario Maggi</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Florence</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Clinica Urologica - Azienda Ospedaliero-Universitaria Careggi</name>
      <address>
        <city>Florence</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Gacci M, Corona G, Salvi M, Vignozzi L, McVary KT, Kaplan SA, Roehrborn CG, Serni S, Mirone V, Carini M, Maggi M. A systematic review and meta-analysis on the use of phosphodiesterase 5 inhibitors alone or in combination with alpha-blockers for lower urinary tract symptoms due to benign prostatic hyperplasia. Eur Urol. 2012 May;61(5):994-1003. doi: 10.1016/j.eururo.2012.02.033. Epub 2012 Feb 25.</citation>
    <PMID>22405510</PMID>
  </reference>
  <reference>
    <citation>Gacci M, Vittori G, Tosi N, Siena G, Rossetti MA, Lapini A, Vignozzi L, Serni S, Maggi M, Carini M. A randomized, placebo-controlled study to assess safety and efficacy of vardenafil 10 mg and tamsulosin 0.4 mg vs. tamsulosin 0.4 mg alone in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. J Sex Med. 2012 Jun;9(6):1624-33. doi: 10.1111/j.1743-6109.2012.02718.x. Epub 2012 Apr 17.</citation>
    <PMID>22510238</PMID>
  </reference>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>September 22, 2014</study_first_submitted>
  <study_first_submitted_qc>September 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 30, 2014</study_first_posted>
  <last_update_submitted>April 27, 2021</last_update_submitted>
  <last_update_submitted_qc>April 27, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 28, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Florence</investigator_affiliation>
    <investigator_full_name>Mario Maggi</investigator_full_name>
    <investigator_title>Full Professor of Endocrinology</investigator_title>
  </responsible_party>
  <keyword>Phosphodiesterase 5 Inhibitors</keyword>
  <keyword>BPH/LUTS</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prostatic Hyperplasia</mesh_term>
    <mesh_term>Hyperplasia</mesh_term>
    <mesh_term>Lower Urinary Tract Symptoms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tadalafil</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/NCT02252367
org study id: ANDRO-AOUC-2014-01
nct id: NCT02252367
lead sponsor: 
collaborator: 
has dmc: No
At present time several preclinical and clinical study have demonstrated the safety and
      efficacy of PDE5 (phosphodiesterase type 5)-inhibitors for LUTS/BPH (lower urinary tract
      symptoms/benign prostatic hyperplasia) patients with or without erectile dysfunction.
      However, the link between clinical outcomes (symptoms scores), functional activity
      (urodynamic findings) and molecular pathways, in particular regarding inflammatory pattern
      (molecular analyses), has not been previously investigated.

      Aim of present study is to assess, for the first time in literature, changes in pressure flow
      study (PFS) and changes in molecular profile of prostatic tissue (inflammatory and tissue
      remodeling markers) in men treated for 12 weeks with tadalafil 5 mg compared with placebo and
      to correlate these data with changes in symptoms scores (IPSS, International Prostatic
      Symptoms Score) in men with LUTS secondary to BPH refractory to alpha blockers.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Improvement of LUTS/BPH symptoms
time frame: 12 weeks
description: BPH-associated inflammatory symptoms will be assessed by using the National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI). BPH-associated LUTS will be assessed by using International Prostate Symptom Score (IPSS).
measure: Improvement of pressure flow study (PFS) parameters
time frame: 12 weeks
description: Maximum flow rate (Qmax), average flow rate (Qave), voided volume (Vcomp), post void residual volume (PVR) will be evaluated. An abdominal ultrasound immediately after voiding for uroflowmetry will be performed in order to determine the PVR.
measure: Volumetric change of the prostate
time frame: 12 weeks
description: Prostate volume as assessed by transrectal ultrasound
measure: Change in prostate inhomogeneity and in the number of prostatic macrocalcifications
time frame: 12 weeks
description: BPH-associated prostate inhomogeneity and presence of micro-calcifications will be assessed by using male genital tract male genital tract colour-Doppler ultrasonography.
measure: Variation in genic expression of prostatic inflammation markers
time frame: 12 weeks
description: BPH-associated prostate inflammation, fibrosis, and hypoxia will be measured by immunohistochemical and quantitative RT-PCR (qRT-PCR) analyses of inflammatory-, fibrosis- and hypoxia-related markers.
measure: Variation in serum inflammation markers CRP (C-reactive protein) and ESR (Erythrocyte Sedimentation Rate)
time frame: 12 weeks
description: CRP measured on serum and ESR measured on blood drawn at baseline and after 12 weeks
measure: Improvement in metabolic profile
time frame: 12 weeks
description: Metabolic parameters will be evaluated (glycaemia, insulinemia, total cholesterol, HDL, triglycerides, HbA1c, mean arterial pressure, waist circumference, body mass index)
measure: Variation in seminal plasma IL-8 (interleukin-8) levels
time frame: 12 weeks
description: Seminal IL-8, a chemokine involved in male genital tract infection/inflammation, will be evaluated.
measure: Improvement in erectile function
time frame: 12 weeks
description: Erectile function will be assessed by using the International Index of Erectile Function-5 (IIEF-5) score.
arm group label: Tadalafil
arm group type: Experimental
description: 43 male subjects affected by BPH (benign prostatic hyperplasia) planned for simple prostatectomy will be randomized to tadalafil 5 mg - 1 film-coated tablet orally once daily for 12 weeks.
arm group label: Placebo
arm group type: Placebo Comparator
description: 43 male subjects affected by BPH (benign prostatic hyperplasia) planned for simple prostatectomy will be randomized to placebo.
intervention type: Drug
intervention name: Tadalafil
description: Tadalafil 5 mg once daily for 12 weeks.
arm group label: Tadalafil
other name: Cialis
intervention type: Other
intervention name: Placebo
description: Placebo tablet once daily for 12 weeks.
arm group label: Placebo
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Mario Maggi
role: Principal Investigator
affiliation: University of Florence
facility: 
country: Italy
citation: Gacci M, Corona G, Salvi M, Vignozzi L, McVary KT, Kaplan SA, Roehrborn CG, Serni S, Mirone V, Carini M, Maggi M. A systematic review and meta-analysis on the use of phosphodiesterase 5 inhibitors alone or in combination with alpha-blockers for lower urinary tract symptoms due to benign prostatic hyperplasia. Eur Urol. 2012 May;61(5):994-1003. doi: 10.1016/j.eururo.2012.02.033. Epub 2012 Feb 25.
PMID: 22405510
citation: Gacci M, Vittori G, Tosi N, Siena G, Rossetti MA, Lapini A, Vignozzi L, Serni S, Maggi M, Carini M. A randomized, placebo-controlled study to assess safety and efficacy of vardenafil 10 mg and tamsulosin 0.4 mg vs. tamsulosin 0.4 mg alone in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. J Sex Med. 2012 Jun;9(6):1624-33. doi: 10.1111/j.1743-6109.2012.02718.x. Epub 2012 Apr 17.
PMID: 22510238
responsible party type: Principal Investigator
investigator affiliation: University of Florence
investigator full name: Mario Maggi
investigator title: Full Professor of Endocrinology
mesh term: Prostatic Hyperplasia
mesh term: Hyperplasia
mesh term: Lower Urinary Tract Symptoms
mesh term: Tadalafil