<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/NCT02185274</url>
  </required_header>
  <id_info>
    <org_study_id>MPIP-ENDO1</org_study_id>
    <nct_id>NCT02185274</nct_id>
  </id_info>
  <brief_title>Observational Study on Metabolism and Psychopathology in Transsexual Patients</brief_title>
  <official_title>Observational Study on the Short- and Long-term Effects of Cross-sex-hormone Treatment on Metabolism and Psychopathology in Transsexuals Patients.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Max-Planck-Institute of Psychiatry</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Erlangen-Nürnberg Medical School</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Institute for Sex Research and Forensic Psychiatry, Hamburg, Germany</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hormon-und Stoffwechselzentrum München, Munich, Germany</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Max-Planck-Institute of Psychiatry</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Gender identity disorders (also known as transsexualism) is defined as a condition in which a&#xD;
      person with apparently normal somatic sexual differentiation is convinced that he or she is&#xD;
      actually a member of the other sex. Most patients therefore undergo so called cross-sex&#xD;
      hormone treatment. Treatment protocols follow international consensus statements but vary&#xD;
      considerably between different centres and countries since no prospective and controlled&#xD;
      trials are available on this subject and recommendations are mainly based on retrospective&#xD;
      data analysis and experience of the individual centres. Applying high doses of testosterone&#xD;
      to biological females and vice versa high doses of estradiol to biological males definitely&#xD;
      impacts myriads of body functions, from which it has to be assumed that only a minority has&#xD;
      already been elucidated so far. Especially in male-to-female-transsexuals there seems to be&#xD;
      an increased risk for the development of mood disorders and cardiometabolic comorbidities. In&#xD;
      this multi-center observational study we want to investigate, if there is any difference with&#xD;
      regard to these outcomes, according to the varying standards of cross-sex hormone treatment&#xD;
      between the different centers. Different outcome measures described below will be assessed&#xD;
      each time during routine visits at the different centers.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 2013</start_date>
  <completion_date type="Actual">November 30, 2019</completion_date>
  <primary_completion_date type="Actual">October 31, 2019</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>Incidence of depressive and anxious symptoms following initiation of cross-sex hormone treatment</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Incidence of depressive and anxious symptoms by means of clinical interview and questionnaires in the the study period defined by different cut-off points in the point scales of the corresponding questionnaire (Beck Depression Inventory II = BDII and Symptomcheckliste bei psychischen Störungen = SCL90 for depression and State and Trait Anxiety Inventory = STAI-X1, X2 for anxiety). A comparison will then be done between the different treatment modes.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Differences in the effects of the different treatment types on cardiometabolic parameters</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Differences in the effects of the different treatment types (differing in dose, application route and type of antiandrogen used) on cardiometabolic risk-parameters such as BMI, body-composition, fasting Insulin, fasting glucose, triglycerides, cholesterol, intima media thickness.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Effects of cross-sex hormone treatment on cortisol secretion by hair cortisol measurements</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Assessment of cortisol secretion by a hair sample which provides information about the mean cortisol secretion during the last months. One cm of scalp hair resembles approximately 1 month of growth. This may provide additional information concerning overall cortisol secretion during the last 3 months. One small hair will be sampled by scalp and this will be analysed in regard to psychological and metabolic profiles.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effects of cross-sex hormone treatment on stress-response by means of Dex/CRH-testing</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>The Dex/CRH-Test has been in use for several years for testing the physiological cortisol-response in psychiatric and neurologic patients and is performed on a routine basis in the Max-Planck Institute for Psychiatry in patients suffering from depressive disorders. It is assumed that regulation of cortisol secretion and responsiveness of the hypothalamus-pituitary-adrenal (HPA)-axis is pathophysiologically related to depression. The test has been proven to be save. Common transient side-effects include flushing, palpitation, tachypnoea and feeling of warmth which usually resolve within minutes without further intervention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Genetic predictors for treatment response</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Predictive value of different polymorphism in genes such as the ERa, ERb and AR (Androgen Receptor), GR (Glucocorticoid-Receptor) or genes involved in steroid metabolism and function on metabolic profiles, breast development and psychiatric outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effects of cross-sex hormone treatment on the metabolome</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Differences in plasma and urine metabolome in plasma such as amino acids; carbohydrates and related; catecholamines and related; complex lipids and related; energy metabolism and organic acids; fatty acids (free and from lipids); purines, pyrimidines and related; steroids and related; vitamins, cofactors and related.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effects of cross-sex hormone treatment on peripheral neurotrophins</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Effects of cross-sex hormone treatment on serum Brain-Derived Neurotrophic Factor (BDNF) levels will be assessed in regular intervals during routine visits.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Association of hair cortisol and cortisol response during dex/crh-testing with psychopathology-scores assessed by clinical interview and questionnaires</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>The following interviews will be used:&#xD;
The MINI-PLUS interview assessing DSM axis I disorders [57].&#xD;
The SCID-II interview assessing DSM axis II disorders&#xD;
The following questionaires will be used&#xD;
• stress coping (SVF-78)&#xD;
Personality:&#xD;
personality (EPQ, TPQ,NEO-FFI)&#xD;
self-reported quality of life (SF-36)&#xD;
subjective body experience (FBeK)&#xD;
self concept (SKI)&#xD;
social support (B-Lor, FSOZ-U)&#xD;
early life trauma (CTQ)&#xD;
Psychopathology:&#xD;
State-Trait Anxiety Inventory (STAI Form X1, STAI Form X2)&#xD;
Depressive symptoms (BDI II)&#xD;
Psychopathology in general (SCL-90)&#xD;
Associations of cortisol- and ACTH response following dex/crg-challenge will be analyzed with regard to the presence of depression assessed by clinical interview and psychopathology scores assessed by BDI and STAIX. The other questionnaires will be used for multidimensional modelling.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Predictive value of hair cortisol and cortisol response in dex/crh-testing treatment for depression and anxiety</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Predictive value of hair cortisol 3 month at baseline and after treatment initiation and cortisol response at baseline and after 3 month after treatment initiation during dex/crh-testing for 12 month incidence of depressive or anxiety disorders assessed by clinical interview and questionnaires.&#xD;
The following interviews will be used:&#xD;
The MINI-PLUS interview assessing DSM axis I disorders [57].&#xD;
The SCID-II interview assessing DSM axis II disorders&#xD;
The following questionaires will be used&#xD;
State-Trait Anxiety Inventory (STAI Form X1, STAI Form X2)&#xD;
Depressive symptoms (BDI II)&#xD;
Psychopathology in general (SCL-90)</description>
  </secondary_outcome>
  <enrollment type="Actual">100</enrollment>
  <condition>Transsexualism</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      -  2 x 10ml serum&#xD;
&#xD;
        -  10ml urine&#xD;
&#xD;
        -  Hair sample&#xD;
&#xD;
        -  7,5ml EDTA-Blood for DNA and plasma&#xD;
&#xD;
        -  2,5ml blood for mRNA-Analysis&#xD;
&#xD;
        -  8,5ml stabilized serum&#xD;
&#xD;
        -  Stool sample (2-5ml)&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients will be recruited from the outpatient clinics of the corresponding centres. Every&#xD;
        patient is eligible who has not yet received any cross-sex hormone treatment. Patients will&#xD;
        be invited to participate at the regular visit after which it is planned to start hormone&#xD;
        treatment. Further visits will follow the regular check-up visits in the corresponding&#xD;
        centers.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion criteria&#xD;
&#xD;
          -  Patients with the diagnosis gender identity disorder (ICD-10: F64.0), who have given&#xD;
             written informed consent following adequate oral and written information.&#xD;
&#xD;
        General Exclusion criteria&#xD;
&#xD;
          -  Patients below the age of 18&#xD;
&#xD;
          -  Legally incompetent patients&#xD;
&#xD;
          -  Prior intake of cross-sex hormones&#xD;
&#xD;
          -  Missing written informed consent&#xD;
&#xD;
          -  Intersexuality&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Matthias K Auer, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Max Planck Insitute of Psychiatry, Department of Neuroendocrinology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Gynaecological department of the University hospital of Erlangen</name>
      <address>
        <city>Erlangen</city>
        <zip>91054</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institute for Sex Research and Forensic Psychiatry</name>
      <address>
        <city>Hamburg</city>
        <zip>20246</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hormon- und Stoffwechselzentrum München</name>
      <address>
        <city>Munich</city>
        <zip>80333</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>June 18, 2014</study_first_submitted>
  <study_first_submitted_qc>July 3, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 9, 2014</study_first_posted>
  <last_update_submitted>February 24, 2020</last_update_submitted>
  <last_update_submitted_qc>February 24, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 25, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Transsexualism</keyword>
  <keyword>Cross-sex hormone treatment</keyword>
  <keyword>Sex hormones</keyword>
  <keyword>Mood</keyword>
  <keyword>Stress</keyword>
  <keyword>Cortisol</keyword>
  <keyword>Cardiovascular</keyword>
  <keyword>Metabolome</keyword>
  <!-- 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/NCT02185274
org study id: MPIP-ENDO1
nct id: NCT02185274
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
Gender identity disorders (also known as transsexualism) is defined as a condition in which a
      person with apparently normal somatic sexual differentiation is convinced that he or she is
      actually a member of the other sex. Most patients therefore undergo so called cross-sex
      hormone treatment. Treatment protocols follow international consensus statements but vary
      considerably between different centres and countries since no prospective and controlled
      trials are available on this subject and recommendations are mainly based on retrospective
      data analysis and experience of the individual centres. Applying high doses of testosterone
      to biological females and vice versa high doses of estradiol to biological males definitely
      impacts myriads of body functions, from which it has to be assumed that only a minority has
      already been elucidated so far. Especially in male-to-female-transsexuals there seems to be
      an increased risk for the development of mood disorders and cardiometabolic comorbidities. In
      this multi-center observational study we want to investigate, if there is any difference with
      regard to these outcomes, according to the varying standards of cross-sex hormone treatment
      between the different centers. Different outcome measures described below will be assessed
      each time during routine visits at the different centers.
observational model: Cohort
time perspective: Prospective
measure: Incidence of depressive and anxious symptoms following initiation of cross-sex hormone treatment
time frame: Up to 5 years
description: Incidence of depressive and anxious symptoms by means of clinical interview and questionnaires in the the study period defined by different cut-off points in the point scales of the corresponding questionnaire (Beck Depression Inventory II = BDII and Symptomcheckliste bei psychischen Störungen = SCL90 for depression and State and Trait Anxiety Inventory = STAI-X1, X2 for anxiety). A comparison will then be done between the different treatment modes.
measure: Differences in the effects of the different treatment types on cardiometabolic parameters
time frame: Up to 5 years
description: Differences in the effects of the different treatment types (differing in dose, application route and type of antiandrogen used) on cardiometabolic risk-parameters such as BMI, body-composition, fasting Insulin, fasting glucose, triglycerides, cholesterol, intima media thickness.
measure: Effects of cross-sex hormone treatment on cortisol secretion by hair cortisol measurements
time frame: Up to 5 years
description: Assessment of cortisol secretion by a hair sample which provides information about the mean cortisol secretion during the last months. One cm of scalp hair resembles approximately 1 month of growth. This may provide additional information concerning overall cortisol secretion during the last 3 months. One small hair will be sampled by scalp and this will be analysed in regard to psychological and metabolic profiles.
measure: Effects of cross-sex hormone treatment on stress-response by means of Dex/CRH-testing
time frame: Up to 5 years
description: The Dex/CRH-Test has been in use for several years for testing the physiological cortisol-response in psychiatric and neurologic patients and is performed on a routine basis in the Max-Planck Institute for Psychiatry in patients suffering from depressive disorders. It is assumed that regulation of cortisol secretion and responsiveness of the hypothalamus-pituitary-adrenal (HPA)-axis is pathophysiologically related to depression. The test has been proven to be save. Common transient side-effects include flushing, palpitation, tachypnoea and feeling of warmth which usually resolve within minutes without further intervention.
measure: Genetic predictors for treatment response
time frame: Up to 5 years
description: Predictive value of different polymorphism in genes such as the ERa, ERb and AR (Androgen Receptor), GR (Glucocorticoid-Receptor) or genes involved in steroid metabolism and function on metabolic profiles, breast development and psychiatric outcome.
measure: Effects of cross-sex hormone treatment on the metabolome
time frame: Up to 5 years
description: Differences in plasma and urine metabolome in plasma such as amino acids; carbohydrates and related; catecholamines and related; complex lipids and related; energy metabolism and organic acids; fatty acids (free and from lipids); purines, pyrimidines and related; steroids and related; vitamins, cofactors and related.
measure: Effects of cross-sex hormone treatment on peripheral neurotrophins
time frame: Up to 5 years
description: Effects of cross-sex hormone treatment on serum Brain-Derived Neurotrophic Factor (BDNF) levels will be assessed in regular intervals during routine visits.
measure: Association of hair cortisol and cortisol response during dex/crh-testing with psychopathology-scores assessed by clinical interview and questionnaires
time frame: Up to 5 years
description: The following interviews will be used:
The MINI-PLUS interview assessing DSM axis I disorders [57].
The SCID-II interview assessing DSM axis II disorders
The following questionaires will be used
• stress coping (SVF-78)
Personality:
personality (EPQ, TPQ,NEO-FFI)
self-reported quality of life (SF-36)
subjective body experience (FBeK)
self concept (SKI)
social support (B-Lor, FSOZ-U)
early life trauma (CTQ)
Psychopathology:
State-Trait Anxiety Inventory (STAI Form X1, STAI Form X2)
Depressive symptoms (BDI II)
Psychopathology in general (SCL-90)
Associations of cortisol- and ACTH response following dex/crg-challenge will be analyzed with regard to the presence of depression assessed by clinical interview and psychopathology scores assessed by BDI and STAIX. The other questionnaires will be used for multidimensional modelling.
measure: Predictive value of hair cortisol and cortisol response in dex/crh-testing treatment for depression and anxiety
time frame: Up to 5 years
description: Predictive value of hair cortisol 3 month at baseline and after treatment initiation and cortisol response at baseline and after 3 month after treatment initiation during dex/crh-testing for 12 month incidence of depressive or anxiety disorders assessed by clinical interview and questionnaires.
The following interviews will be used:
The MINI-PLUS interview assessing DSM axis I disorders [57].
The SCID-II interview assessing DSM axis II disorders
The following questionaires will be used
State-Trait Anxiety Inventory (STAI Form X1, STAI Form X2)
Depressive symptoms (BDI II)
Psychopathology in general (SCL-90)
-  2 x 10ml serum

        -  10ml urine

        -  Hair sample

        -  7,5ml EDTA-Blood for DNA and plasma

        -  2,5ml blood for mRNA-Analysis

        -  8,5ml stabilized serum

        -  Stool sample (2-5ml)
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Matthias K Auer, MD
role: Principal Investigator
affiliation: Max Planck Insitute of Psychiatry, Department of Neuroendocrinology
facility: 
facility: 
facility: 
country: Germany
responsible party type: Sponsor