<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/NCT02991209</url>
  </required_header>
  <id_info>
    <org_study_id>010815Testis</org_study_id>
    <nct_id>NCT02991209</nct_id>
  </id_info>
  <brief_title>Study of Testosterone vs Placebo in Testicular Cancer Survivors</brief_title>
  <acronym>Einstein</acronym>
  <official_title>A Randomized Double-blind Study of Testosterone Replacement Therapy or Placebo in Testicular Cancer Survivors With Mild Leydig Cell Insufficiency (Einstein-intervention)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mikkel Bandak</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Rigshospitalet, Denmark</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The overall purpose of the study is to evaluate the effect of 12 months testosterone&#xD;
      replacement therapy in testicular cancer survivors with mild Leydig Cell Insufficiency in&#xD;
      order to reduce the risk of cardiovascular disease.&#xD;
&#xD;
      The primary study objective is to evaluate changes in insulin sensitivity. The secondary&#xD;
      study objective is to evaluate changes in the prevalence of metabolic syndrome, body&#xD;
      composition, systemic inflammation and symptoms of testosterone deficiency.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single-center, randomized, double-blind, placebo-controlled intervention study,&#xD;
      designed to evaluate the effect of testosterone replacement therapy in testicular cancer&#xD;
      survivors with mild Leydig Cell Insufficiency.&#xD;
&#xD;
      70 subjects will be randomized to receive either testosterone replacement therapy or placebo.&#xD;
      The subjects will be invited for an information meeting where informed consent is signed. If&#xD;
      a subject is suitable for participation in the trial, subject will be randomized to&#xD;
      testosterone replacement therapy or placebo and baseline investigations will be performed.&#xD;
      Afterwards, a 52-weeks treatment period begins in which subjects receive a daily dose of&#xD;
      testosterone or placebo. Dose adjustment will be made three times during the first 8 weeks of&#xD;
      the study. Evaluation of primary and secondary endpoints will be performed after 26 weeks, at&#xD;
      the end of treatment (52 weeks) and three months after completion of treatment (week 64).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2016</start_date>
  <completion_date type="Actual">June 2019</completion_date>
  <primary_completion_date type="Actual">June 2019</primary_completion_date>
  <phase>Phase 2/Phase 3</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>Changes in insulin sensitivity</measure>
    <time_frame>1 year</time_frame>
    <description>Evaluation of changes in two hours plasma glucose investigated by Oral Glucose Tolerance Test (OGTT)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in fasting plasma lipids between baseline and 52 weeks</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in BMD and fat percent between baseline 52 weeks</measure>
    <time_frame>1 year</time_frame>
    <description>BMD and body composition evaluated by DXA-scan</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in systemic inflammation between baseline and 52 weeks</measure>
    <time_frame>1 year</time_frame>
    <description>Analysis of tnf-alfa, interleukine 1-beta, interleukine 1, interleukine 6, interleukine 8</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in plasma-adipocytokines between baseline and 52 weeks</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in fasting plasma glucose between baseline and 52 weeks</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Quality of life between baseline and 52 weeks.</measure>
    <time_frame>1 year</time_frame>
    <description>EORTC-QLQ C30</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events evaluated by the Common Terminology Criteria for Adverse Events Version 4.0</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in prevalence of metabolic syndrome between baseline and 52 weeks</measure>
    <time_frame>1 year</time_frame>
    <description>According to NCEP-ATPIII criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in haemoglobin A1c between baseline and 52 weeks</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in plasma insulin between baseline and 52 weeks</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in fatigue between baseline and 52 weeks</measure>
    <time_frame>1 year</time_frame>
    <description>MFI-20 (Multidimensional Fatigue Inventory)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Anxiety and depression between baseline and 52 weeks</measure>
    <time_frame>1 year</time_frame>
    <description>HADS (Hospital Anxiety and Depression Scale)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Symptoms of low levels of testosterone, erectile dysfunction between baseline and 52 weeks</measure>
    <time_frame>1 year</time_frame>
    <description>IIEF-15 (International Index of Erectile Dysfunction)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">69</enrollment>
  <condition>Metabolic Syndrome</condition>
  <condition>Testicular Cancer</condition>
  <condition>Leydig Cell Failure in Adult</condition>
  <arm_group>
    <arm_group_label>Tostran 2%</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1 years treatment with transdermal Tostran 2%</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>1 years treatment with placebo gel</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Testosterone</intervention_name>
    <arm_group_label>Tostran 2%</arm_group_label>
    <other_name>Tostran</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebos</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Signed informed consent.&#xD;
&#xD;
          -  Previous treatment for testicular cancer.&#xD;
&#xD;
          -  No signs of relapse 1 year after last treatment (orchiectomy, radiotherapy,&#xD;
             chemotherapy).&#xD;
&#xD;
          -  Free testosterone &lt; the age-adjusted median and &gt; -2 standard deviations (SD) from the&#xD;
             age-adjusted median and LH &gt; 2 SD from the age-adjusted median.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Treatment with testosterone within the last 6 months.&#xD;
&#xD;
          -  Contraindications to testosterone treatment (prostate cancer, prostate specific&#xD;
             antigen (PSA)&gt; 4 ng/mL), malignancy suspect prostate by digital rectal examination,&#xD;
             Alanine aminotransferase (ALT)&gt; 1.5 upper reference level, Erythrocyte Volume Fraction&#xD;
             (EVF) &gt; 50%.&#xD;
&#xD;
          -  Breast cancer.&#xD;
&#xD;
          -  Symptomatic obstructive sleep apnoea syndrome&#xD;
&#xD;
          -  Heart failure &gt; NYHA II.&#xD;
&#xD;
          -  Uncontrolled hypertension: (Systolic blood pressure &gt; 160 mm Hg despite&#xD;
             antihypertensive treatment, measured at two separate occasions)&#xD;
&#xD;
          -  Inability to understand information about the trial&#xD;
&#xD;
          -  Participation in any other clinical trial&#xD;
&#xD;
          -  Allergy for the active substance or additives in Tostran or placebo.&#xD;
&#xD;
          -  Known diabetes mellitus, or diabetes mellitus detected at screening or baseline tests.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Rigshospitalet</name>
      <address>
        <city>Copenhagen</city>
        <zip>2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>November 25, 2016</study_first_submitted>
  <study_first_submitted_qc>December 9, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 13, 2016</study_first_posted>
  <last_update_submitted>March 5, 2020</last_update_submitted>
  <last_update_submitted_qc>March 5, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 6, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Rigshospitalet, Denmark</investigator_affiliation>
    <investigator_full_name>Mikkel Bandak</investigator_full_name>
    <investigator_title>MD, Research Fellow</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Testicular Neoplasms</mesh_term>
    <mesh_term>Metabolic Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Testosterone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT02991209
org study id: 010815Testis
nct id: NCT02991209
lead sponsor: 
has dmc: No
The overall purpose of the study is to evaluate the effect of 12 months testosterone
      replacement therapy in testicular cancer survivors with mild Leydig Cell Insufficiency in
      order to reduce the risk of cardiovascular disease.

      The primary study objective is to evaluate changes in insulin sensitivity. The secondary
      study objective is to evaluate changes in the prevalence of metabolic syndrome, body
      composition, systemic inflammation and symptoms of testosterone deficiency.
This is a single-center, randomized, double-blind, placebo-controlled intervention study,
      designed to evaluate the effect of testosterone replacement therapy in testicular cancer
      survivors with mild Leydig Cell Insufficiency.

      70 subjects will be randomized to receive either testosterone replacement therapy or placebo.
      The subjects will be invited for an information meeting where informed consent is signed. If
      a subject is suitable for participation in the trial, subject will be randomized to
      testosterone replacement therapy or placebo and baseline investigations will be performed.
      Afterwards, a 52-weeks treatment period begins in which subjects receive a daily dose of
      testosterone or placebo. Dose adjustment will be made three times during the first 8 weeks of
      the study. Evaluation of primary and secondary endpoints will be performed after 26 weeks, at
      the end of treatment (52 weeks) and three months after completion of treatment (week 64).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Changes in insulin sensitivity
time frame: 1 year
description: Evaluation of changes in two hours plasma glucose investigated by Oral Glucose Tolerance Test (OGTT)
measure: Changes in fasting plasma lipids between baseline and 52 weeks
time frame: 1 year
measure: Changes in BMD and fat percent between baseline 52 weeks
time frame: 1 year
description: BMD and body composition evaluated by DXA-scan
measure: Changes in systemic inflammation between baseline and 52 weeks
time frame: 1 year
description: Analysis of tnf-alfa, interleukine 1-beta, interleukine 1, interleukine 6, interleukine 8
measure: Changes in plasma-adipocytokines between baseline and 52 weeks
time frame: 1 year
measure: Changes in fasting plasma glucose between baseline and 52 weeks
time frame: 1 year
measure: Changes in Quality of life between baseline and 52 weeks.
time frame: 1 year
description: EORTC-QLQ C30
measure: Adverse events evaluated by the Common Terminology Criteria for Adverse Events Version 4.0
time frame: 1 year
measure: Changes in prevalence of metabolic syndrome between baseline and 52 weeks
time frame: 1 year
description: According to NCEP-ATPIII criteria
measure: Changes in haemoglobin A1c between baseline and 52 weeks
time frame: 1 year
measure: Changes in plasma insulin between baseline and 52 weeks
time frame: 1 year
measure: Changes in fatigue between baseline and 52 weeks
time frame: 1 year
description: MFI-20 (Multidimensional Fatigue Inventory)
measure: Changes in Anxiety and depression between baseline and 52 weeks
time frame: 1 year
description: HADS (Hospital Anxiety and Depression Scale)
measure: Changes in Symptoms of low levels of testosterone, erectile dysfunction between baseline and 52 weeks
time frame: 1 year
description: IIEF-15 (International Index of Erectile Dysfunction)
arm group label: Tostran 2%
arm group type: Experimental
description: 1 years treatment with transdermal Tostran 2%
arm group label: Placebo
arm group type: Placebo Comparator
description: 1 years treatment with placebo gel
intervention type: Drug
intervention name: Testosterone
arm group label: Tostran 2%
other name: Tostran
intervention type: Drug
intervention name: Placebos
arm group label: Placebo
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
facility: 
country: Denmark
responsible party type: Sponsor-Investigator
investigator affiliation: Rigshospitalet, Denmark
investigator full name: Mikkel Bandak
investigator title: MD, Research Fellow
mesh term: Testicular Neoplasms
mesh term: Metabolic Syndrome
mesh term: Testosterone
sharing ipd: No