<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/NCT04492553</url>
  </required_header>
  <id_info>
    <org_study_id>Vitality</org_study_id>
    <nct_id>NCT04492553</nct_id>
  </id_info>
  <brief_title>Gonadal Dysfunction in Male Long-term Survivors of Malignant Lymphoma; Vitality</brief_title>
  <acronym>Vitality</acronym>
  <official_title>Gonadal Dysfunction in Male Long-term Survivors of Malignant Lymphoma; A Prospective Non Randomised Open Label Multicenter Phase Two Study in Male Longterm Survivors of Malignant Lymphoma (Vitality)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Lars Møller Pedersen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Besins Healthcare</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Copenhagen University Hospital at Herlev</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Zealand University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Herlev Hospital</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>
      This study is a prospective non-randomised open label multicenter phase two study in male&#xD;
      long-term survivors of malignant lymphoma including Hodgkin Lymphoma (HL) and Diffuse Large&#xD;
      B-Cell Lymphoma (DLBCL). The study aims to assess whether low levels of testosterone in the&#xD;
      blood of patients cured for aggressive lymphoma, can be effectively treated with Testosterone&#xD;
      gel, and if treatment with testosterone can improve their general quality of life. The&#xD;
      investigators hypothesize that patients will develop sexual dysfunction and poor quality of&#xD;
      life when suffering from untreated reduced level of testosterone.&#xD;
&#xD;
      Cancer treatment is increasingly effective and the overall survival higher, which makes&#xD;
      issues like sexuality and long-term quality of life more and more important to address in&#xD;
      cured cancer patients. Patient sexuality and quality of life is measured by three&#xD;
      questionnaires, and serum testosterone level, during one year of treatment with Testogel. The&#xD;
      intention is to show that future follow-up visits should include focus on sexuality and serum&#xD;
      testosterone, so relevant patients can be identified and treated for their hormonedeficiency&#xD;
      without delay. The expected follow-up program include questionnaires and blood samples, which&#xD;
      are easily implemented and without great cost.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Diffuse large B-cell lymphoma and Hodgkin Lymphoma are two aggressive lymphomas often treated&#xD;
      with doxorubicin containing chemotherapy. Doxorubicin is an anthracycline and is known to be&#xD;
      toxic to both Leydig Cells of the testes and hormone-producing cells of the hypothalamus.&#xD;
      Therefore, patients treated with this drug are at risk of developing hypogonadism. Standard&#xD;
      follow-up programs do not include analysis of hormone levels or treatment of hypogonadism.&#xD;
      With this study the aim is to investigate the effect and toxicity of treatment with exogenous&#xD;
      testosterone in male long-term survivors of malignant lymphoma, to clarify whether it is&#xD;
      relevant to include serum testosterone and potentially testosterone replacement therapy in&#xD;
      standard follow-up programs.&#xD;
&#xD;
      Our Hypothesis:&#xD;
&#xD;
      Hypothesis 1: A significant proportion of long-term male survivors of HL and DLBCL have&#xD;
      impaired quality of life (QoL) due to sexual dysfunction.&#xD;
&#xD;
      Hypothesis 2: A significant proportion of long-term male survivors of HL and DLBCL have&#xD;
      reduced levels of testosterone.&#xD;
&#xD;
      Hypothesis 3: A significant relationship between QoL, sexual dysfunction and testosterone&#xD;
      levels exists.&#xD;
&#xD;
      Hypothesis 4: Substitution with testosterone in carefully selected subgroups will improve&#xD;
      sexual function and QoL.&#xD;
&#xD;
      Hypothesis 5: Treatment with testosterone in this setting is safe with acceptable toxicity.&#xD;
&#xD;
      To assess efficacy and safety of treatment with testosterone replacement therapy on&#xD;
      hypogonadism in lymphoma patients, blood tests and questionnaires are completed throughout&#xD;
      one year of treatment. To assess patient sexuality and quality of life, 3 questionnaires are&#xD;
      included; the European Organisation for Research and Treatment of Cancer (EORTC) Quality of&#xD;
      Life Questionnaire Core 30 (QLQ C30) for general quality of life, EORTC Sexual Health&#xD;
      Questionnaire 22 (SHQ-22) for sexual health and International index of erectile function with&#xD;
      5 questions (IIEF-5) for sexual function.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 1, 2021</start_date>
  <completion_date type="Actual">November 10, 2022</completion_date>
  <primary_completion_date type="Actual">November 10, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Cured lymphoma patients who suffer from hypogonadism identified in a previous study, Vitality-Obs, will be treated with testosterone replacement therapy for the duration of one year. Patients are treated after standard indication and in standard doses. All will receive the same treatment.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Effect of testosterone on QLQ C-30 score</measure>
    <time_frame>1 year</time_frame>
    <description>Effect of treatment with testosterone on QLQ C30 score from baseline to end of study (12 months after inclusion). Scores a measured from 3 scales; function, symptoms and global health. Highest score is 100. Scoring after an algorithm.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Effect of testosterone on QLQ SHQ-22 score</measure>
    <time_frame>1 year</time_frame>
    <description>Effect of treatment with testosterone on QLQ SHQ-22 score from baseline to end of study (12 months after inclusion). Scores a measured from 2 scales; function and symptoms. Highest score is 100. Scoring after an algorithm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of testosterone on IIEF-5 score</measure>
    <time_frame>1 year</time_frame>
    <description>Effect of treatment with testosterone on symptoms of hypogonadism (IIEF-5 score) from baseline to end of study (12 months after inclusion). IIEF-5 is based on 5 questions. Scores range from 5 to 25, Lower scores mean higher degree of erectile dysfunction.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time from baseline until significant change in questionnaire scores are seen</measure>
    <time_frame>1 year</time_frame>
    <description>Time from baseline to a significant decrease in QLQ C30, QLQ SHQ-22 (a little change 5-10 points difference, moderate change 10-20, very much change above 20) and IIEF-5 (changing from at least one category to the next) score is seen.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>S-testosteron change</measure>
    <time_frame>1 year</time_frame>
    <description>S-testosterone from baseline to end of study (12 months after inclusion).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Testosterone dose needed for significant change in scores</measure>
    <time_frame>1 year</time_frame>
    <description>Testosterone dose needed before significant decrease in QLQ C30, QLQ SHQ-22 and IIEF-5 score. Dosing range from 1 to 2 sachets of Testogel per day.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">7</enrollment>
  <condition>Hypogonadism</condition>
  <arm_group>
    <arm_group_label>Testogel</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All patients will be treated with Testogel. Starting dose is 1 sachet of gel daily applied to the skin of arms, thighs or abdomen. Dose adjustments are made after serum-levels of testosterone. All patients will be treated for a total of 52 weeks, unless they exit the study early because of side-effects or other reasons.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AndroGel</intervention_name>
    <description>Treatment indication: hypogonadism after cancer treatment. Dosage: 1-2 sachets a day. Follows standard treatment.</description>
    <arm_group_label>Testogel</arm_group_label>
    <other_name>Testogel</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 18-65 years at inclusion&#xD;
&#xD;
          2. Male&#xD;
&#xD;
          3. Verified diagnosis of de novo DLBCL or classical HL diagnosed between April 2008 and&#xD;
             April 2018 according to World Health Organization (WHO) classification.&#xD;
&#xD;
          4. Completed curative intent first line treatment with anthracycline-containing&#xD;
             chemotherapy with or without consolidating radiotherapy, with disease in complete&#xD;
             remission at End of Treatment (EOT) Positron Emissions Tomography / Computerized&#xD;
             Tomography (PET/CT) at least one year prior to inclusion.&#xD;
&#xD;
          5. Literate in Danish&#xD;
&#xD;
          6. Serum testosterone level below threshold for age adjusted reference level used in the&#xD;
             local laboratory at the time of inclusion.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Concurrent low-grade lymphoma&#xD;
&#xD;
          2. Current or prior lymphoproliferative disease of the central nervous system (CNS)&#xD;
&#xD;
          3. Current or prior lymphoproliferative disease of the testes&#xD;
&#xD;
          4. Contraindications for the treatment with testosterone: Verified prostate cancer /&#xD;
             Prostate Specific Antigen (PSA) &gt; 3 ng/ml, cancer of the mammae, primary liver cancer&#xD;
             or polycythaemia vera / Hct &gt; 0,49.&#xD;
&#xD;
          5. Mental or physical conditions that are expected to prevent the necessary &quot;compliance&quot;&#xD;
             and/or &quot;adherence&quot; in relation to the study procedures&#xD;
&#xD;
          6. Current or prior anabolic steroid drug abuse&#xD;
&#xD;
          7. Treatment with second line chemotherapy or high dose therapy.&#xD;
&#xD;
          8. Known allergies to additives in Testogel.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Gender is based on social security number</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lars Møller Pedersen, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Zealand University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Copenhagen University Hospital</name>
      <address>
        <city>Copenhagen</city>
        <zip>2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Herlev University Hospital</name>
      <address>
        <city>Herlev</city>
        <zip>2730</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zealand University Hospital</name>
      <address>
        <city>Roskilde</city>
        <zip>4000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>July 27, 2020</study_first_submitted>
  <study_first_submitted_qc>July 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 30, 2020</study_first_posted>
  <last_update_submitted>November 28, 2022</last_update_submitted>
  <last_update_submitted_qc>November 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 29, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Herlev Hospital</investigator_affiliation>
    <investigator_full_name>Lars Møller Pedersen</investigator_full_name>
    <investigator_title>Senior consultant</investigator_title>
  </responsible_party>
  <keyword>quality of life</keyword>
  <keyword>sexuality</keyword>
  <keyword>sexual health</keyword>
  <keyword>EORTC</keyword>
  <keyword>QLQ-C30</keyword>
  <keyword>SHQ-22</keyword>
  <keyword>IIEF-5</keyword>
  <keyword>hypogonadism</keyword>
  <keyword>testosterone</keyword>
  <keyword>cancer</keyword>
  <keyword>lymphoma</keyword>
  <keyword>diffuse large b-cell lymphoma</keyword>
  <keyword>hodgkin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Hypogonadism</mesh_term>
    <mesh_term>Gonadal Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Testosterone</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/NCT04492553
org study id: Vitality
nct id: NCT04492553
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
This study is a prospective non-randomised open label multicenter phase two study in male
      long-term survivors of malignant lymphoma including Hodgkin Lymphoma (HL) and Diffuse Large
      B-Cell Lymphoma (DLBCL). The study aims to assess whether low levels of testosterone in the
      blood of patients cured for aggressive lymphoma, can be effectively treated with Testosterone
      gel, and if treatment with testosterone can improve their general quality of life. The
      investigators hypothesize that patients will develop sexual dysfunction and poor quality of
      life when suffering from untreated reduced level of testosterone.

      Cancer treatment is increasingly effective and the overall survival higher, which makes
      issues like sexuality and long-term quality of life more and more important to address in
      cured cancer patients. Patient sexuality and quality of life is measured by three
      questionnaires, and serum testosterone level, during one year of treatment with Testogel. The
      intention is to show that future follow-up visits should include focus on sexuality and serum
      testosterone, so relevant patients can be identified and treated for their hormonedeficiency
      without delay. The expected follow-up program include questionnaires and blood samples, which
      are easily implemented and without great cost.
Diffuse large B-cell lymphoma and Hodgkin Lymphoma are two aggressive lymphomas often treated
      with doxorubicin containing chemotherapy. Doxorubicin is an anthracycline and is known to be
      toxic to both Leydig Cells of the testes and hormone-producing cells of the hypothalamus.
      Therefore, patients treated with this drug are at risk of developing hypogonadism. Standard
      follow-up programs do not include analysis of hormone levels or treatment of hypogonadism.
      With this study the aim is to investigate the effect and toxicity of treatment with exogenous
      testosterone in male long-term survivors of malignant lymphoma, to clarify whether it is
      relevant to include serum testosterone and potentially testosterone replacement therapy in
      standard follow-up programs.

      Our Hypothesis:

      Hypothesis 1: A significant proportion of long-term male survivors of HL and DLBCL have
      impaired quality of life (QoL) due to sexual dysfunction.

      Hypothesis 2: A significant proportion of long-term male survivors of HL and DLBCL have
      reduced levels of testosterone.

      Hypothesis 3: A significant relationship between QoL, sexual dysfunction and testosterone
      levels exists.

      Hypothesis 4: Substitution with testosterone in carefully selected subgroups will improve
      sexual function and QoL.

      Hypothesis 5: Treatment with testosterone in this setting is safe with acceptable toxicity.

      To assess efficacy and safety of treatment with testosterone replacement therapy on
      hypogonadism in lymphoma patients, blood tests and questionnaires are completed throughout
      one year of treatment. To assess patient sexuality and quality of life, 3 questionnaires are
      included; the European Organisation for Research and Treatment of Cancer (EORTC) Quality of
      Life Questionnaire Core 30 (QLQ C30) for general quality of life, EORTC Sexual Health
      Questionnaire 22 (SHQ-22) for sexual health and International index of erectile function with
      5 questions (IIEF-5) for sexual function.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Cured lymphoma patients who suffer from hypogonadism identified in a previous study, Vitality-Obs, will be treated with testosterone replacement therapy for the duration of one year. Patients are treated after standard indication and in standard doses. All will receive the same treatment.
primary purpose: Treatment
masking: None (Open Label)
measure: Effect of testosterone on QLQ C-30 score
time frame: 1 year
description: Effect of treatment with testosterone on QLQ C30 score from baseline to end of study (12 months after inclusion). Scores a measured from 3 scales; function, symptoms and global health. Highest score is 100. Scoring after an algorithm.
measure: Effect of testosterone on QLQ SHQ-22 score
time frame: 1 year
description: Effect of treatment with testosterone on QLQ SHQ-22 score from baseline to end of study (12 months after inclusion). Scores a measured from 2 scales; function and symptoms. Highest score is 100. Scoring after an algorithm.
measure: Effect of testosterone on IIEF-5 score
time frame: 1 year
description: Effect of treatment with testosterone on symptoms of hypogonadism (IIEF-5 score) from baseline to end of study (12 months after inclusion). IIEF-5 is based on 5 questions. Scores range from 5 to 25, Lower scores mean higher degree of erectile dysfunction.
measure: Time from baseline until significant change in questionnaire scores are seen
time frame: 1 year
description: Time from baseline to a significant decrease in QLQ C30, QLQ SHQ-22 (a little change 5-10 points difference, moderate change 10-20, very much change above 20) and IIEF-5 (changing from at least one category to the next) score is seen.
measure: S-testosteron change
time frame: 1 year
description: S-testosterone from baseline to end of study (12 months after inclusion).
measure: Testosterone dose needed for significant change in scores
time frame: 1 year
description: Testosterone dose needed before significant decrease in QLQ C30, QLQ SHQ-22 and IIEF-5 score. Dosing range from 1 to 2 sachets of Testogel per day.
arm group label: Testogel
arm group type: Experimental
description: All patients will be treated with Testogel. Starting dose is 1 sachet of gel daily applied to the skin of arms, thighs or abdomen. Dose adjustments are made after serum-levels of testosterone. All patients will be treated for a total of 52 weeks, unless they exit the study early because of side-effects or other reasons.
intervention type: Drug
intervention name: AndroGel
description: Treatment indication: hypogonadism after cancer treatment. Dosage: 1-2 sachets a day. Follows standard treatment.
arm group label: Testogel
other name: Testogel
criteria: 
gender: Male
gender based: Yes
gender description: Gender is based on social security number
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Lars Møller Pedersen, MD
role: Principal Investigator
affiliation: Zealand University Hospital
facility: 
facility: 
facility: 
country: Denmark
responsible party type: Sponsor-Investigator
investigator affiliation: Herlev Hospital
investigator full name: Lars Møller Pedersen
investigator title: Senior consultant
mesh term: Lymphoma
mesh term: Hypogonadism
mesh term: Gonadal Disorders
mesh term: Testosterone