<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/NCT02248467</url>
  </required_header>
  <id_info>
    <org_study_id>ANDRO-AOUC-2013-01</org_study_id>
    <nct_id>NCT02248467</nct_id>
  </id_info>
  <brief_title>Study of the Effect of Testosterone Treatment on Metabolic Parameters and Urinary Symptoms in Bariatric Patients</brief_title>
  <official_title>Study of the Effect of Testosterone Replacement Therapy on Metabolic Parameters, Prostatic Inflammation Symptoms and Lower Urinary Tract Symptoms (LUTS) in Hypogonadal Obese Subjects Eligible for Bariatric Surgery.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Florence</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Florence</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary purpose of the study is to evaluate, in obese and hypogonadal patients eligible&#xD;
      for bariatric surgery, the effect of testosterone replacement therapy in improving lower&#xD;
      urinary tract symptoms (LUTS) assessed using the IPSS (International Prostate Symptom Score)&#xD;
      questionnaire, compared to hypogonadal untreated subjects and eugonadal subjects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary objective:&#xD;
&#xD;
      - Evaluation in obese and hypogonadal patients candidates for bariatric surgery of the effect&#xD;
      of testosterone replacement therapy in improving the symptoms of LUTS (assessed using the&#xD;
      IPSS questionnaire) compared to hypogonadal untreated subjects and eugonadal subjects.&#xD;
&#xD;
      Secondary objectives:&#xD;
&#xD;
        -  Evaluation of the effect of testosterone in obese and hypogonadal patients candidates&#xD;
           for bariatric surgery in improving metabolic parameters (glycaemia, oral glucose&#xD;
           tolerance test, HbA1c, total cholesterol, HDL cholesterol, triglycerides, arterial&#xD;
           pressure, BMI, waist circumference) compared to hypogonadal untreated subjects and&#xD;
           eugonadal subjects&#xD;
&#xD;
        -  Evaluation of the effect of testosterone in obese and hypogonadal patients candidates&#xD;
           for bariatric surgery in improving uroflowmetric parameters compared to hypogonadal&#xD;
           untreated subjects and eugonadal subjects&#xD;
&#xD;
        -  Evaluation of the effect of testosterone in obese and hypogonadal patients candidates&#xD;
           for bariatric surgery on the ultrasound characteristics of the prostate&#xD;
           (macro-calcifications, intraprostatic arterial velocity, volume of the prostate gland).&#xD;
&#xD;
        -  Evaluation of the effect of testosterone in obese and hypogonadal patients candidates&#xD;
           for bariatric surgery on pre-adipocytes isolated from visceral adipose tissue samples&#xD;
           collected during surgical procedures, as compared to hypogonadal untreated subjects and&#xD;
           eugonadal subjects.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>May 2013</start_date>
  <completion_date type="Actual">June 2018</completion_date>
  <primary_completion_date type="Actual">December 2017</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>IPSS score (LUTS) improvement</measure>
    <time_frame>1 yr after surgery</time_frame>
    <description>For each patient the presence of an improvement of LUTS, assessed by IPSS score, will be evaluated by calculating the difference between the scores of the IPSS questionnaire administered at V1 compared to that administered to V0, V2 as compared to V1, or V3 as compared to V2. The mean of this change will be then compared between different groups (eugonadal; untreated hypogonadal; treated hypogonadal)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Presence of Metabolic Syndrome</measure>
    <time_frame>1 yr after surgery</time_frame>
    <description>The diagnosis of MetS parameters will be re-evaluated to confirm the presence or absence (waist circumference, dyslipidemia, blood pressure, fasting plasma glucose)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volumetric change of the prostate</measure>
    <time_frame>1 yr after surgery</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the number of prostatic macrocalcifications</measure>
    <time_frame>1 yr after surgery</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the peak of arterial velocity at the colour-doppler ultrasound of the prostate</measure>
    <time_frame>1 yr after surgery</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement of sexual function</measure>
    <time_frame>1 yr after surgery</time_frame>
    <description>Improvement of sexual function will be assessed by evaluating differences in the score obtained at the IIEF-5 (International Index of Erectile Function), a questionnaire which assesses erectile function by 5 questions with a score from 0 to 5, by giving 5 to the best erectile function. Scores range from 1 to 25, and a cut-off of 21 defines erectile dysfunction (score &lt;21).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement of symptoms of hypogonadism</measure>
    <time_frame>1 yr after surgery</time_frame>
    <description>Improvement of sexual function will be assessed by evaluating differences in the score obtained at the AMS (Aging Male's symptoms). This questionnaire consists of 17 questions which investigate the disturbances of the psychological, somatic and sexual domain; for each question the patient gives a numerical answer ranging from 1 (no symptoms) to 5 (very severe symptoms). The assessment of symptoms is obtained from the numerical sum of 17 responses. The symptoms are classified as: • absent: score 17 to 26; • mild: score 27 to 36; • moderate: score 37 to 49; • severe: score ≥ 50.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Preadipocyte dysfunction assessed in preadipocyte isolated from visceral adipose tissue obtained during bariatric surgery</measure>
    <time_frame>1 yr after surgery</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Variations in histomorphometric and molecular parameters of hepatic tissue obtained during bariatric surgery</measure>
    <time_frame>1 yr after surgery</time_frame>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">100</enrollment>
  <condition>Obesity</condition>
  <condition>Hypogonadism</condition>
  <condition>Prostatic Hyperplasia</condition>
  <condition>Insulin Resistance</condition>
  <arm_group>
    <arm_group_label>eugonadal</arm_group_label>
    <description>50 eugonadal subjects</description>
  </arm_group>
  <arm_group>
    <arm_group_label>untreated hypogonadal</arm_group_label>
    <description>25 asymptomatic hypogonadal subjects</description>
  </arm_group>
  <arm_group>
    <arm_group_label>treated hypogonadal</arm_group_label>
    <description>25 symptomatic hypogonadal subjects treated - In the present study, we decided to monitor only sexual symptoms of androgen deficiency due to the fact that testosterone replacement therapy (TRT) should be expected to improve them in the time span until surgery. These patients will be treated with TRT as per clinical practice.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Male adults subjects suffering from severe obesity in a waiting list for bariatric surgery&#xD;
        for weight loss will be considered eligible.&#xD;
&#xD;
        The diagnosis of hypogonadism will be defined by levels of total testosterone &lt;12nmol / l&#xD;
        or free testosterone &lt;225 pmol / L (calculated according to the formula of Vermeulen).&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male subjects&#xD;
&#xD;
          -  Age between 25 and 65 years&#xD;
&#xD;
          -  Obese men, candidate to a bariatric surgery (body mass index (BMI) is ≥40 kg/m2, or if&#xD;
             their BMI is &gt;35 kg/m2 and they suffer from other life-threatening co-morbidities such&#xD;
             as Type 2 Diabetes Mellitus, hypertension and cardiovascular disease)&#xD;
&#xD;
          -  Men with LUTS defined by: IPSS ≥ 8.&#xD;
&#xD;
          -  Evidence of a personally signed and dated informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Bladder failure or Neurogenic bladder&#xD;
&#xD;
          -  LUT disease (Urethral stenosis, diverticula)&#xD;
&#xD;
          -  LUT surgery (Prostatectomy, bladder neck surgery, TURP)&#xD;
&#xD;
          -  Severe systemic disease&#xD;
&#xD;
          -  Previous or concomitant neoplasm&#xD;
&#xD;
          -  Unable to consistently and accurately complete the protocol&#xD;
&#xD;
          -  Abuse alcohol or drugs&#xD;
&#xD;
          -  Psychiatric disease&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>25 Years</minimum_age>
    <maximum_age>65 Years</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>Ambulatori Medicina della Sessualità e Andrologia</name>
      <address>
        <city>Florence</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Lotti F, Corona G, Colpi GM, Filimberti E, Degli Innocenti S, Mancini M, Baldi E, Noci I, Forti G, Adorini L, Maggi M. Elevated body mass index correlates with higher seminal plasma interleukin 8 levels and ultrasonographic abnormalities of the prostate in men attending an andrology clinic for infertility. J Endocrinol Invest. 2011 Nov;34(10):e336-42. doi: 10.3275/7855. Epub 2011 Jul 7.</citation>
    <PMID>21738005</PMID>
  </reference>
  <reference>
    <citation>Filippi S, Vignozzi L, Morelli A, Chavalmane AK, Sarchielli E, Fibbi B, Saad F, Sandner P, Ruggiano P, Vannelli GB, Mannucci E, Maggi M. Testosterone partially ameliorates metabolic profile and erectile responsiveness to PDE5 inhibitors in an animal model of male metabolic syndrome. J Sex Med. 2009 Dec;6(12):3274-88. doi: 10.1111/j.1743-6109.2009.01467.x. Epub 2009 Sep 1.</citation>
    <PMID>19732305</PMID>
  </reference>
  <reference>
    <citation>Vignozzi L, Morelli A, Sarchielli E, Comeglio P, Filippi S, Cellai I, Maneschi E, Serni S, Gacci M, Carini M, Piccinni MP, Saad F, Adorini L, Vannelli GB, Maggi M. Testosterone protects from metabolic syndrome-associated prostate inflammation: an experimental study in rabbit. J Endocrinol. 2012 Jan;212(1):71-84. doi: 10.1530/JOE-11-0289. Epub 2011 Oct 18.</citation>
    <PMID>22010203</PMID>
  </reference>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>September 17, 2014</study_first_submitted>
  <study_first_submitted_qc>September 22, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2014</study_first_posted>
  <last_update_submitted>October 11, 2018</last_update_submitted>
  <last_update_submitted_qc>October 11, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 12, 2018</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>Testosterone replacement therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prostatic Hyperplasia</mesh_term>
    <mesh_term>Insulin Resistance</mesh_term>
    <mesh_term>Hypogonadism</mesh_term>
    <mesh_term>Hyperplasia</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/NCT02248467
org study id: ANDRO-AOUC-2013-01
nct id: NCT02248467
lead sponsor: 
has dmc: No
The primary purpose of the study is to evaluate, in obese and hypogonadal patients eligible
      for bariatric surgery, the effect of testosterone replacement therapy in improving lower
      urinary tract symptoms (LUTS) assessed using the IPSS (International Prostate Symptom Score)
      questionnaire, compared to hypogonadal untreated subjects and eugonadal subjects.
Primary objective:

      - Evaluation in obese and hypogonadal patients candidates for bariatric surgery of the effect
      of testosterone replacement therapy in improving the symptoms of LUTS (assessed using the
      IPSS questionnaire) compared to hypogonadal untreated subjects and eugonadal subjects.

      Secondary objectives:

        -  Evaluation of the effect of testosterone in obese and hypogonadal patients candidates
           for bariatric surgery in improving metabolic parameters (glycaemia, oral glucose
           tolerance test, HbA1c, total cholesterol, HDL cholesterol, triglycerides, arterial
           pressure, BMI, waist circumference) compared to hypogonadal untreated subjects and
           eugonadal subjects

        -  Evaluation of the effect of testosterone in obese and hypogonadal patients candidates
           for bariatric surgery in improving uroflowmetric parameters compared to hypogonadal
           untreated subjects and eugonadal subjects

        -  Evaluation of the effect of testosterone in obese and hypogonadal patients candidates
           for bariatric surgery on the ultrasound characteristics of the prostate
           (macro-calcifications, intraprostatic arterial velocity, volume of the prostate gland).

        -  Evaluation of the effect of testosterone in obese and hypogonadal patients candidates
           for bariatric surgery on pre-adipocytes isolated from visceral adipose tissue samples
           collected during surgical procedures, as compared to hypogonadal untreated subjects and
           eugonadal subjects.
observational model: Cohort
time perspective: Prospective
measure: IPSS score (LUTS) improvement
time frame: 1 yr after surgery
description: For each patient the presence of an improvement of LUTS, assessed by IPSS score, will be evaluated by calculating the difference between the scores of the IPSS questionnaire administered at V1 compared to that administered to V0, V2 as compared to V1, or V3 as compared to V2. The mean of this change will be then compared between different groups (eugonadal; untreated hypogonadal; treated hypogonadal)
measure: Presence of Metabolic Syndrome
time frame: 1 yr after surgery
description: The diagnosis of MetS parameters will be re-evaluated to confirm the presence or absence (waist circumference, dyslipidemia, blood pressure, fasting plasma glucose)
measure: Volumetric change of the prostate
time frame: 1 yr after surgery
measure: Change in the number of prostatic macrocalcifications
time frame: 1 yr after surgery
measure: Change in the peak of arterial velocity at the colour-doppler ultrasound of the prostate
time frame: 1 yr after surgery
measure: Improvement of sexual function
time frame: 1 yr after surgery
description: Improvement of sexual function will be assessed by evaluating differences in the score obtained at the IIEF-5 (International Index of Erectile Function), a questionnaire which assesses erectile function by 5 questions with a score from 0 to 5, by giving 5 to the best erectile function. Scores range from 1 to 25, and a cut-off of 21 defines erectile dysfunction (score <21).
measure: Improvement of symptoms of hypogonadism
time frame: 1 yr after surgery
description: Improvement of sexual function will be assessed by evaluating differences in the score obtained at the AMS (Aging Male's symptoms). This questionnaire consists of 17 questions which investigate the disturbances of the psychological, somatic and sexual domain; for each question the patient gives a numerical answer ranging from 1 (no symptoms) to 5 (very severe symptoms). The assessment of symptoms is obtained from the numerical sum of 17 responses. The symptoms are classified as: • absent: score 17 to 26; • mild: score 27 to 36; • moderate: score 37 to 49; • severe: score ≥ 50.
measure: Preadipocyte dysfunction assessed in preadipocyte isolated from visceral adipose tissue obtained during bariatric surgery
time frame: 1 yr after surgery
measure: Variations in histomorphometric and molecular parameters of hepatic tissue obtained during bariatric surgery
time frame: 1 yr after surgery
arm group label: eugonadal
description: 50 eugonadal subjects
arm group label: untreated hypogonadal
description: 25 asymptomatic hypogonadal subjects
arm group label: treated hypogonadal
description: 25 symptomatic hypogonadal subjects treated - In the present study, we decided to monitor only sexual symptoms of androgen deficiency due to the fact that testosterone replacement therapy (TRT) should be expected to improve them in the time span until surgery. These patients will be treated with TRT as per clinical practice.
study pop: 
sampling method: Probability Sample
criteria: 
gender: Male
minimum age: 25 Years
maximum age: 65 Years
healthy volunteers: No
last name: Mario Maggi
role: Principal Investigator
affiliation: University of Florence
facility: 
country: Italy
citation: Lotti F, Corona G, Colpi GM, Filimberti E, Degli Innocenti S, Mancini M, Baldi E, Noci I, Forti G, Adorini L, Maggi M. Elevated body mass index correlates with higher seminal plasma interleukin 8 levels and ultrasonographic abnormalities of the prostate in men attending an andrology clinic for infertility. J Endocrinol Invest. 2011 Nov;34(10):e336-42. doi: 10.3275/7855. Epub 2011 Jul 7.
PMID: 21738005
citation: Filippi S, Vignozzi L, Morelli A, Chavalmane AK, Sarchielli E, Fibbi B, Saad F, Sandner P, Ruggiano P, Vannelli GB, Mannucci E, Maggi M. Testosterone partially ameliorates metabolic profile and erectile responsiveness to PDE5 inhibitors in an animal model of male metabolic syndrome. J Sex Med. 2009 Dec;6(12):3274-88. doi: 10.1111/j.1743-6109.2009.01467.x. Epub 2009 Sep 1.
PMID: 19732305
citation: Vignozzi L, Morelli A, Sarchielli E, Comeglio P, Filippi S, Cellai I, Maneschi E, Serni S, Gacci M, Carini M, Piccinni MP, Saad F, Adorini L, Vannelli GB, Maggi M. Testosterone protects from metabolic syndrome-associated prostate inflammation: an experimental study in rabbit. J Endocrinol. 2012 Jan;212(1):71-84. doi: 10.1530/JOE-11-0289. Epub 2011 Oct 18.
PMID: 22010203
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: Insulin Resistance
mesh term: Hypogonadism
mesh term: Hyperplasia