<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/NCT02229617</url>
  </required_header>
  <id_info>
    <org_study_id>H14-00862</org_study_id>
    <nct_id>NCT02229617</nct_id>
  </id_info>
  <brief_title>Subcutaneous Testosterone Project</brief_title>
  <acronym>STP</acronym>
  <official_title>A Pilot Study of Subcutaneous vs. Intramuscular Testosterone for Gender Affirming Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of British Columbia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Vancouver Coastal Health Research Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of British Columbia</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      For people who identify as transgender, there is a strong sense that they were born into the&#xD;
      wrong body and that their outward looking body does not match how they truly feel about&#xD;
      themselves. They feel male, not female and have always felt that way. There is a great deal&#xD;
      of discomfort or dysphoria about looking and feeling female, and there is a strong desire to&#xD;
      achieve a more masculine appearance. While surgery, clothing and hair for example, can help a&#xD;
      person appear more like a male, many transgender males will want to take testosterone to make&#xD;
      them feel and look more masculine.&#xD;
&#xD;
      This usually involves injecting testosterone into a muscle every 1-2 weeks for many years.&#xD;
      Intramuscular injections can often be uncomfortable or painful, and requires the patient to&#xD;
      be taught how to inject themselves. Or somebody else has to do it. There is a growing trend&#xD;
      in some transgender men to give their injection just below the skin or subcutaneously (like&#xD;
      insulin in a diabetic), because it is less uncomfortable but we don't really know if&#xD;
      testosterone gets into the blood in the same way. At least one clinic in the US already&#xD;
      suggests that patients can use the subcutaneous method but there is almost no research to&#xD;
      show it's the same as intramuscular.&#xD;
&#xD;
      Our project will be looking at a small group of transgender males who are already on&#xD;
      intramuscular testosterone and then switch them over to the same dose of subcutaneous&#xD;
      testosterone, and then compare their levels of testosterone. If those levels are similar,&#xD;
      then patients may chose the less uncomfortable subcutaneous injection.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Rationale:&#xD;
&#xD;
      In caring for transgender males (born female but identify as male), intramuscular (IM)&#xD;
      testosterone is considered standard of care if they elect therapy to transition. Yet, IM&#xD;
      testosterone has limitations: discomfort; a modest amount of teaching; bleeding concerns if&#xD;
      the patient is on anticoagulants; and fluctuations in circulating serum testosterone. Erratic&#xD;
      absorption may also led to variability in mood and energy. Due to these limitations, there is&#xD;
      a trend, especially in younger patients, to use the more comfortable subcutaneous (SC) route.&#xD;
      However, there are little data suggesting equivalency of SC to IM testosterone and virtually&#xD;
      no data in transgender males.&#xD;
&#xD;
      Hypothesis:&#xD;
&#xD;
      In transgender males, SC testosterone will yield similar pharmacokinetics and better&#xD;
      tolerability when compared to IM testosterone.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
        1. To validate, using a cross-over design, whether pharmacokinetic parameters of SC vs. IM&#xD;
           testosterone administration are similar.&#xD;
&#xD;
        2. To characterize, using a validated pain questionnaire and patient diary, tolerability of&#xD;
           SC vs. IM testosterone.&#xD;
&#xD;
      Research Plan:&#xD;
&#xD;
      Patients (19-59 years old) on a weekly self-injection schedule of either T cypionate or&#xD;
      enanthate will be included. Patients with medical instability, recent or imminent surgery&#xD;
      will be excluded. Twenty-five patients will be recruited from the 6 local Vancouver Coastal&#xD;
      HealthTrans Primary Care physicians' clinics.&#xD;
&#xD;
      Using a cross-over design, trough serum testosterone levels from the IM technique will be&#xD;
      determined weekly for 3 weeks. Patients will then switch to SC injection of the same&#xD;
      testosterone ester and dosage, and weekly trough levels measured for another 8 weeks. These&#xD;
      trough measurements will allow us to determine attainment of steady-state testosterone&#xD;
      levels. During the 3rd and 11th week, serial testosterone levels will be collected to&#xD;
      generate noncompartmental pharmacokinetic parameters, which will be compared between the two&#xD;
      techniques. Patients will complete a validated pain analogue questionnaire during the initial&#xD;
      3-week IM phase, and again during weeks 2 and 8 of the SC phase and maintain a diary&#xD;
      throughout the study. Descriptive and inferential statistics will be used with p&lt;0.05&#xD;
      denoting significance.&#xD;
&#xD;
      Significance: If SC testosterone yields similar pharmacokinetics and better tolerability than&#xD;
      IM testosterone, it will reduce the perceived barrier of IM injections and mitigate&#xD;
      non-compliance. There are potential cost savings as patients will not require a clinician to&#xD;
      inject. The findings may also be generalized to hypogonadal males. Ultimately, results are&#xD;
      crucial to designing a larger multi-center study to provide definitive dosing&#xD;
      recommendations.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2015</start_date>
  <completion_date type="Actual">May 2016</completion_date>
  <primary_completion_date type="Actual">May 2016</primary_completion_date>
  <phase>Phase 1/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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Serum Testosterone (Total)</measure>
    <time_frame>11 weeks</time_frame>
    <description>To compare the steady state levels of total serum testosterone using the Subcutaneous (SC) and Intramuscular (IM) injection routes in a group of transgender males who are already on stable IM dosages.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of serum testosterone</measure>
    <time_frame>2 weeks</time_frame>
    <description>We will be measuring alternate day serum testosterone levels during the subjects final week of IM testosterone injections (week #3) and the final week of SC testosterone injections (week #11).</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Tolerability and discomfort assessment</measure>
    <time_frame>11 weeks</time_frame>
    <description>Study participants will complete a weekly questionnaire regarding tolerability and discomfort, as well as a final questionnaire asking for preferred method of injection.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Gender Dysphoria</condition>
  <arm_group>
    <arm_group_label>Injectable testosterone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>We will take a group of transgender males, already on a stable dosage of intramuscular testosterone, and then using their same type and dosage, switch them to the subcutaneous injection route. Weekly trough (just before their weekly injection) levels of total serum testosterone will be taken to compare the steady states of those two injection routes.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Subcutaneous testosterone</intervention_name>
    <arm_group_label>Injectable testosterone</arm_group_label>
    <other_name>Testosterone cypionate</other_name>
    <other_name>Testosteron enanthate</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Transgender males or identifying along the male spectrum&#xD;
&#xD;
          -  Currently on stable doses of weekly IM testosterone&#xD;
&#xD;
          -  Using either Testosterone cypionate or enanthate&#xD;
&#xD;
          -  Between 19-59 years old&#xD;
&#xD;
          -  Stable doses of regular medications&#xD;
&#xD;
          -  Receive their transgender care from one of five(5) Vancouver-based physicians who&#xD;
             specialize in transgender care (Three Bridges or Raven Song Community Health Centres).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Medically or psychiatrically unstable&#xD;
&#xD;
          -  Recent or imminent surgery (6-8 weeks) that has or may affect testosterone dosage&#xD;
&#xD;
          -  Unable to present for nine(9) weeks of weekly blood work and two(2) weeks of alternate&#xD;
             day blood work&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>59 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mary Ensom, Pharm D/PhD</last_name>
    <role>Study Director</role>
    <affiliation>University of British Columbia, Faculty of Pharmaceutical Sciences</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Three Bridges Community Health Centre</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V6Z 1W2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Raven Song Community Health Centre</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>June 2016</verification_date>
  <study_first_submitted>August 28, 2014</study_first_submitted>
  <study_first_submitted_qc>August 28, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 1, 2014</study_first_posted>
  <last_update_submitted>June 2, 2016</last_update_submitted>
  <last_update_submitted_qc>June 2, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">June 6, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Intramuscular testosterone</keyword>
  <keyword>Subcutaneous testosterone</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gender Dysphoria</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>
  <!-- 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/NCT02229617
org study id: H14-00862
nct id: NCT02229617
lead sponsor: 
collaborator: 
has dmc: No
For people who identify as transgender, there is a strong sense that they were born into the
      wrong body and that their outward looking body does not match how they truly feel about
      themselves. They feel male, not female and have always felt that way. There is a great deal
      of discomfort or dysphoria about looking and feeling female, and there is a strong desire to
      achieve a more masculine appearance. While surgery, clothing and hair for example, can help a
      person appear more like a male, many transgender males will want to take testosterone to make
      them feel and look more masculine.

      This usually involves injecting testosterone into a muscle every 1-2 weeks for many years.
      Intramuscular injections can often be uncomfortable or painful, and requires the patient to
      be taught how to inject themselves. Or somebody else has to do it. There is a growing trend
      in some transgender men to give their injection just below the skin or subcutaneously (like
      insulin in a diabetic), because it is less uncomfortable but we don't really know if
      testosterone gets into the blood in the same way. At least one clinic in the US already
      suggests that patients can use the subcutaneous method but there is almost no research to
      show it's the same as intramuscular.

      Our project will be looking at a small group of transgender males who are already on
      intramuscular testosterone and then switch them over to the same dose of subcutaneous
      testosterone, and then compare their levels of testosterone. If those levels are similar,
      then patients may chose the less uncomfortable subcutaneous injection.
Rationale:

      In caring for transgender males (born female but identify as male), intramuscular (IM)
      testosterone is considered standard of care if they elect therapy to transition. Yet, IM
      testosterone has limitations: discomfort; a modest amount of teaching; bleeding concerns if
      the patient is on anticoagulants; and fluctuations in circulating serum testosterone. Erratic
      absorption may also led to variability in mood and energy. Due to these limitations, there is
      a trend, especially in younger patients, to use the more comfortable subcutaneous (SC) route.
      However, there are little data suggesting equivalency of SC to IM testosterone and virtually
      no data in transgender males.

      Hypothesis:

      In transgender males, SC testosterone will yield similar pharmacokinetics and better
      tolerability when compared to IM testosterone.

      Objectives:

        1. To validate, using a cross-over design, whether pharmacokinetic parameters of SC vs. IM
           testosterone administration are similar.

        2. To characterize, using a validated pain questionnaire and patient diary, tolerability of
           SC vs. IM testosterone.

      Research Plan:

      Patients (19-59 years old) on a weekly self-injection schedule of either T cypionate or
      enanthate will be included. Patients with medical instability, recent or imminent surgery
      will be excluded. Twenty-five patients will be recruited from the 6 local Vancouver Coastal
      HealthTrans Primary Care physicians' clinics.

      Using a cross-over design, trough serum testosterone levels from the IM technique will be
      determined weekly for 3 weeks. Patients will then switch to SC injection of the same
      testosterone ester and dosage, and weekly trough levels measured for another 8 weeks. These
      trough measurements will allow us to determine attainment of steady-state testosterone
      levels. During the 3rd and 11th week, serial testosterone levels will be collected to
      generate noncompartmental pharmacokinetic parameters, which will be compared between the two
      techniques. Patients will complete a validated pain analogue questionnaire during the initial
      3-week IM phase, and again during weeks 2 and 8 of the SC phase and maintain a diary
      throughout the study. Descriptive and inferential statistics will be used with p<0.05
      denoting significance.

      Significance: If SC testosterone yields similar pharmacokinetics and better tolerability than
      IM testosterone, it will reduce the perceived barrier of IM injections and mitigate
      non-compliance. There are potential cost savings as patients will not require a clinician to
      inject. The findings may also be generalized to hypogonadal males. Ultimately, results are
      crucial to designing a larger multi-center study to provide definitive dosing
      recommendations.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Serum Testosterone (Total)
time frame: 11 weeks
description: To compare the steady state levels of total serum testosterone using the Subcutaneous (SC) and Intramuscular (IM) injection routes in a group of transgender males who are already on stable IM dosages.
measure: Pharmacokinetics of serum testosterone
time frame: 2 weeks
description: We will be measuring alternate day serum testosterone levels during the subjects final week of IM testosterone injections (week #3) and the final week of SC testosterone injections (week #11).
measure: Tolerability and discomfort assessment
time frame: 11 weeks
description: Study participants will complete a weekly questionnaire regarding tolerability and discomfort, as well as a final questionnaire asking for preferred method of injection.
arm group label: Injectable testosterone
arm group type: Active Comparator
description: We will take a group of transgender males, already on a stable dosage of intramuscular testosterone, and then using their same type and dosage, switch them to the subcutaneous injection route. Weekly trough (just before their weekly injection) levels of total serum testosterone will be taken to compare the steady states of those two injection routes.
intervention type: Drug
intervention name: Subcutaneous testosterone
arm group label: Injectable testosterone
other name: Testosterone cypionate
other name: Testosteron enanthate
criteria: 
gender: Male
minimum age: 19 Years
maximum age: 59 Years
healthy volunteers: No
last name: Mary Ensom, Pharm D/PhD
role: Study Director
affiliation: University of British Columbia, Faculty of Pharmaceutical Sciences
facility: 
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Gender Dysphoria
mesh term: Methyltestosterone
mesh term: Testosterone
mesh term: Testosterone undecanoate
mesh term: Testosterone enanthate
mesh term: Testosterone 17 beta-cypionate