<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/NCT03792321</url>
  </required_header>
  <id_info>
    <org_study_id>SBCE-KG-2014-1</org_study_id>
    <nct_id>NCT03792321</nct_id>
  </id_info>
  <brief_title>Study on Effects of Testosterone Replacement Therapy in Hypogonadal Type 2 Diabetic Patients&quot; (SETH2)</brief_title>
  <acronym>SETH2</acronym>
  <official_title>Study on Effects of Testosterone Replacement Therapy in Hypogonadal Type 2</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Medical Centre Ljubljana</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Medical Centre Ljubljana</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>
      Aim of the study was to investigate the effects of testosterone replacement therapy on&#xD;
      components of metabolic syndrome, vascular function and morphology, grade of non-alcoholic&#xD;
      fatty liver disease (NAFLD), bone mineral density (BMD) and health-related quality of life.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Studies have shown that approximately 50 % of older obese males, who are being treated for&#xD;
      diabetes mellitus type 2, also exhibit low testosterone levels. Hypogonadism negatively&#xD;
      affects glycemic control, exacerbates early cardio-vascular disease, causes osteoporosis,&#xD;
      erectile disfunction, reduces lean body mass, accelerates the accumulation of visceral fat&#xD;
      and leads to obesity.&#xD;
&#xD;
      Patients with diabetes mellitus type 2 and confirmed hypogonadism were enrolled into this&#xD;
      randomized, double-blind, placebo-controlled clinical study. Placebo group patients were&#xD;
      receiving placebo throughout the first year of this study and Testosterone group patients&#xD;
      were receiving testosterone undecanoate during first year. Both groups were receiving&#xD;
      testosterone undecanoate throughout the second year of this study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 10, 2014</start_date>
  <completion_date type="Actual">March 5, 2018</completion_date>
  <primary_completion_date type="Actual">March 5, 2015</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>
    <intervention_model_description>55 patients were divided in two groups. P group patients were receiving placebo throughout the first year of this study and T group patients were receiving testosterone. Both groups were receiving TRT throughout the second year.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Effects of testosterone replacement therapy on glycemic control - fasting plasma glucose (FPG) mmol/l</measure>
    <time_frame>FPG was measured at baseline, after 12 months and after 24 months</time_frame>
    <description>The primary outcome measure was change in glycemic control - fasting plasma glucose (FPG) mmol/l</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effects of testosterone replacement therapy on glycemic control - glycated hemoglobin A1c (HbA1c) %</measure>
    <time_frame>HbA1c was measured at baseline, after 12 months and after 24 months</time_frame>
    <description>The primary outcome measure was change in glycemic control - glycated hemoglobin A1c (HbA1c) %</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effects of testosterone replacement therapy on parameters of metabolic syndrome - change in HOMA-IR</measure>
    <time_frame>HOMA-IR was calculated at the baseline, after 12 months and after 24 months of clinical trial.</time_frame>
    <description>The primary outcome measure was change in Homeostasis model assessment of insulin resistance (HOMA-IR)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effects of testosterone replacement therapy on vascular function - change in flow mediated dilatation (FMD) %</measure>
    <time_frame>FMD was measured at baseline, after 12 months and after 24 months</time_frame>
    <description>The primary outcome measure was change in flow mediated dilatation (FMD) % assessed by vascular ultrasound</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effects of testosterone replacement therapy on vascular morphology - intima-media thickness (IMT)</measure>
    <time_frame>IMT was measured at baseline, after 12 months and after 24 months</time_frame>
    <description>The primary outcome measure was change in intima-media thickness (IMT) mm assessed by vascular ultrasound</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Effects of testosterone replacement therapy on non-alcoholic fatty liver disease (NAFLD)</measure>
    <time_frame>Grade of NAFLD was determined at baseline and after 24 months</time_frame>
    <description>The secondary outcome was change in grade of non-alcoholic fatty liver disease (NAFLD) graded as either &quot;none&quot;, &quot;mild&quot;, &quot;moderate&quot; and &quot;severe&quot;, assessed by abdominal ultrasound</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effects of testosterone replacement therapy on bone mineral density (BMD)</measure>
    <time_frame>Change in bone mineral density was measured at baseline and after 24 months</time_frame>
    <description>The secondary outcome was change in bone mineral density assessed by dual-energy x-ray absorptiometry (DXA) g/cm^2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effects of testosterone replacement on total testosterone (TT), calculated free testosterone (cFT), and calculated bioavailable testosterone (BT) concentrations</measure>
    <time_frame>Changes in total testosterone (TT), calculated free testosterone (cFT), and calculated bioavailable testosterone (BT) concentrations were measured baseline, after 12 months and 24 months</time_frame>
    <description>The secondary outcome were changes in total testosterone (TT), calculated free testosterone (cFT), and calculated bioavailable testosterone (BT) concentrations - all in nmol/l</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effects of testosterone replacement on prostate specific antigen (PSA)</measure>
    <time_frame>Prostate specific antigen (PSA) was measured at baseline,3,6,12,15,18 and 24 months</time_frame>
    <description>The secondary outcome was change in prostate specific antigen (PSA) ng/ml</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effects of testosterone replacement on hematocrit</measure>
    <time_frame>Hematocrit was measured at baseline,3,6,12,15,18 and 24 months</time_frame>
    <description>The secondary outcome was change in hematocrit (Hct) %</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">55</enrollment>
  <condition>Hypogonadism, Male</condition>
  <condition>Diabetes Mellitus, Type 2</condition>
  <condition>Obesity</condition>
  <arm_group>
    <arm_group_label>Testosterone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Testosterone arm patients were receiving testosterone undecanoate 1000 mg intramuscular injections two years; according to the protocol every 10 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo arm patients were receiving placebo throughout the first year of this study and testosterone undecanoate 1000 mg intramuscular injections during second year.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Testosterone Undecanoate</intervention_name>
    <description>1000 mg i.m. every 10 weeks</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>Testosterone</arm_group_label>
    <other_name>Nebido</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  men aged &gt; 35 years&#xD;
&#xD;
          -  body mass index &gt; 30 kg/m2&#xD;
&#xD;
          -  confirmed hypogonadism&#xD;
&#xD;
          -  type 2 diabetes mellitus treated with non-insulin therapy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  previously treated hypogonadism&#xD;
&#xD;
          -  the 2 diabetes mellitus treated with insulin therapy&#xD;
&#xD;
          -  a history of current prostate or breast cancer&#xD;
&#xD;
          -  severe benign prostatic hyperplasia&#xD;
&#xD;
          -  elevated prostate-specific antigen (PSA &gt; 4.0 lg/l)&#xD;
&#xD;
          -  severe heart failure&#xD;
&#xD;
          -  acute coronary event or procedure during the six months leading up to the study&#xD;
&#xD;
          -  chronic obstructive lung disease&#xD;
&#xD;
          -  hypothyroidism&#xD;
&#xD;
          -  severe obstructive sleep apnea (OSA)&#xD;
&#xD;
          -  active infection&#xD;
&#xD;
          -  rheumatoid arthritis&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>35 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kristina Groti Antonic, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Medical Centre Ljubljana</affiliation>
  </overall_official>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>December 27, 2018</study_first_submitted>
  <study_first_submitted_qc>January 2, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 3, 2019</study_first_posted>
  <last_update_submitted>January 2, 2019</last_update_submitted>
  <last_update_submitted_qc>January 2, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 4, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University Medical Centre Ljubljana</investigator_affiliation>
    <investigator_full_name>Kristina Groti</investigator_full_name>
    <investigator_title>Principal Investigator; MD, PhD, specialist in Internal medicine</investigator_title>
  </responsible_party>
  <keyword>testosterone</keyword>
  <keyword>hypogonadism</keyword>
  <keyword>diabetes mellitus</keyword>
  <keyword>visceral obesity</keyword>
  <keyword>insulin resistance</keyword>
  <keyword>metabolic syndrome</keyword>
  <keyword>NAFLD</keyword>
  <keyword>endothelial function</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
    <mesh_term>Hypogonadism</mesh_term>
    <mesh_term>Eunuchism</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Methyltestosterone</mesh_term>
    <mesh_term>Testosterone</mesh_term>
    <mesh_term>Testosterone undecanoate</mesh_term>
    <mesh_term>Testosterone enanthate</mesh_term>
    <mesh_term>Testosterone 17 beta-cypionate</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/NCT03792321
org study id: SBCE-KG-2014-1
nct id: NCT03792321
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
Aim of the study was to investigate the effects of testosterone replacement therapy on
      components of metabolic syndrome, vascular function and morphology, grade of non-alcoholic
      fatty liver disease (NAFLD), bone mineral density (BMD) and health-related quality of life.
Studies have shown that approximately 50 % of older obese males, who are being treated for
      diabetes mellitus type 2, also exhibit low testosterone levels. Hypogonadism negatively
      affects glycemic control, exacerbates early cardio-vascular disease, causes osteoporosis,
      erectile disfunction, reduces lean body mass, accelerates the accumulation of visceral fat
      and leads to obesity.

      Patients with diabetes mellitus type 2 and confirmed hypogonadism were enrolled into this
      randomized, double-blind, placebo-controlled clinical study. Placebo group patients were
      receiving placebo throughout the first year of this study and Testosterone group patients
      were receiving testosterone undecanoate during first year. Both groups were receiving
      testosterone undecanoate throughout the second year of this study.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: 55 patients were divided in two groups. P group patients were receiving placebo throughout the first year of this study and T group patients were receiving testosterone. Both groups were receiving TRT throughout the second year.
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Effects of testosterone replacement therapy on glycemic control - fasting plasma glucose (FPG) mmol/l
time frame: FPG was measured at baseline, after 12 months and after 24 months
description: The primary outcome measure was change in glycemic control - fasting plasma glucose (FPG) mmol/l
measure: Effects of testosterone replacement therapy on glycemic control - glycated hemoglobin A1c (HbA1c) %
time frame: HbA1c was measured at baseline, after 12 months and after 24 months
description: The primary outcome measure was change in glycemic control - glycated hemoglobin A1c (HbA1c) %
measure: Effects of testosterone replacement therapy on parameters of metabolic syndrome - change in HOMA-IR
time frame: HOMA-IR was calculated at the baseline, after 12 months and after 24 months of clinical trial.
description: The primary outcome measure was change in Homeostasis model assessment of insulin resistance (HOMA-IR)
measure: Effects of testosterone replacement therapy on vascular function - change in flow mediated dilatation (FMD) %
time frame: FMD was measured at baseline, after 12 months and after 24 months
description: The primary outcome measure was change in flow mediated dilatation (FMD) % assessed by vascular ultrasound
measure: Effects of testosterone replacement therapy on vascular morphology - intima-media thickness (IMT)
time frame: IMT was measured at baseline, after 12 months and after 24 months
description: The primary outcome measure was change in intima-media thickness (IMT) mm assessed by vascular ultrasound
measure: Effects of testosterone replacement therapy on non-alcoholic fatty liver disease (NAFLD)
time frame: Grade of NAFLD was determined at baseline and after 24 months
description: The secondary outcome was change in grade of non-alcoholic fatty liver disease (NAFLD) graded as either "none", "mild", "moderate" and "severe", assessed by abdominal ultrasound
measure: Effects of testosterone replacement therapy on bone mineral density (BMD)
time frame: Change in bone mineral density was measured at baseline and after 24 months
description: The secondary outcome was change in bone mineral density assessed by dual-energy x-ray absorptiometry (DXA) g/cm^2
measure: Effects of testosterone replacement on total testosterone (TT), calculated free testosterone (cFT), and calculated bioavailable testosterone (BT) concentrations
time frame: Changes in total testosterone (TT), calculated free testosterone (cFT), and calculated bioavailable testosterone (BT) concentrations were measured baseline, after 12 months and 24 months
description: The secondary outcome were changes in total testosterone (TT), calculated free testosterone (cFT), and calculated bioavailable testosterone (BT) concentrations - all in nmol/l
measure: Effects of testosterone replacement on prostate specific antigen (PSA)
time frame: Prostate specific antigen (PSA) was measured at baseline,3,6,12,15,18 and 24 months
description: The secondary outcome was change in prostate specific antigen (PSA) ng/ml
measure: Effects of testosterone replacement on hematocrit
time frame: Hematocrit was measured at baseline,3,6,12,15,18 and 24 months
description: The secondary outcome was change in hematocrit (Hct) %
arm group label: Testosterone
arm group type: Active Comparator
description: Testosterone arm patients were receiving testosterone undecanoate 1000 mg intramuscular injections two years; according to the protocol every 10 weeks
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo arm patients were receiving placebo throughout the first year of this study and testosterone undecanoate 1000 mg intramuscular injections during second year.
intervention type: Drug
intervention name: Testosterone Undecanoate
description: 1000 mg i.m. every 10 weeks
arm group label: Placebo
arm group label: Testosterone
other name: Nebido
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: Male
minimum age: 35 Years
maximum age: N/A
healthy volunteers: No
last name: Kristina Groti Antonic, MD, PhD
role: Principal Investigator
affiliation: University Medical Centre Ljubljana
responsible party type: Principal Investigator
investigator affiliation: University Medical Centre Ljubljana
investigator full name: Kristina Groti
investigator title: Principal Investigator; MD, PhD, specialist in Internal medicine
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Hypogonadism
mesh term: Eunuchism
mesh term: Methyltestosterone
mesh term: Testosterone
mesh term: Testosterone undecanoate
mesh term: Testosterone enanthate
mesh term: Testosterone 17 beta-cypionate
sharing ipd: Undecided