<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/NCT03254641</url>
  </required_header>
  <id_info>
    <org_study_id>H-17004362</org_study_id>
    <nct_id>NCT03254641</nct_id>
  </id_info>
  <brief_title>Calciotropic Effects After hCG Stimulation Test</brief_title>
  <official_title>Calciotropic Effects After hCG Stimulation Test</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Martin Blomberg Jensen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Rigshospitalet, Denmark</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</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>
      We have in a pilot study found that serum calcium levels change in response to hCG&#xD;
      stimulation test. We observed that serum calcium level measured at baseline and 72 hours&#xD;
      after hCG stimulation were different in men with gonadal insufficiency referred for this&#xD;
      stimulation test. Now we want to investigate a large cohort of men referred for hCG&#xD;
      stimulation test due to suspected impaired gonadal function.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Introduction:&#xD;
&#xD;
      hCG signals through the LHCGR receptor and is know to stimulate testosterone production. hCG&#xD;
      stimulation tests are therefore used to evaulate the capacity of the testis to respond to&#xD;
      LH/hCG and thereby determine the degree og gonadal insufficiency and need for testosterone&#xD;
      supplementation. Some groups have found LHCRG in extragondal tissues indicating a direct&#xD;
      effect of hCG/LH outside the gonads. We noticed that some men with gonadal insuffciency had a&#xD;
      low calcium level after hCG stimulation test. Now we would like to investigate whether this&#xD;
      putative effect on calcium homeostasis of hCG is due to a direct effect or an indirect effect&#xD;
      through testosterone or other sex steroids that also change in response to hCG stimulation.&#xD;
      Moreover, we would like to clarify whether the chnage in calcium is compensated by classical&#xD;
      regulators such as PTH, 1,25OH2D3, calcitonin, phosphate, CTX, alkaline phosphatase or other&#xD;
      factors.&#xD;
&#xD;
      Aim of study:&#xD;
&#xD;
      The purpose of this study is to describe changes in calcium and calciotropic hormones after&#xD;
      hCG stimulation test&#xD;
&#xD;
      DESIGN This is a prospective observational study&#xD;
&#xD;
      Patients and methods 100 men referred for hCG stimulation test due to suspected gonadal&#xD;
      insuffciency age 18-60 years at Department of growth and reproduction, Rigshospitalet&#xD;
&#xD;
      Exclusion criteria are&#xD;
&#xD;
      intake of high dose calcium (above 1 mg daily) Known Disorders related to calcium metabolism,&#xD;
      hypercalcemia, Granulomatous disease such as Wegener, tuberculosis, etc,&#xD;
&#xD;
      SAMPLE SIZE CALCULATION AND STATISTICS By using a test level of 5% (level of significance),&#xD;
      power of 80% and at least 100 men completing the trial will enable us to detect a change in&#xD;
      calcium of 10%, and a change in serum PTH of 30%.&#xD;
&#xD;
      SCREENING AND TIME COURSE Men referred for hCG stimulation test at ourDepartment will be&#xD;
      screened for eligibility to the study. Those who meet the criteria for participation will be&#xD;
      informed, and if they consent allocated to the study.&#xD;
&#xD;
      Each person will have one blood sampling performed prior to the test and 72 and 96 hours&#xD;
      after the test.&#xD;
&#xD;
      Blood samples Venus blood is drawn preoperatively before hCG administration, 72 and 96 hours&#xD;
      after. Serum will be send for analysis within 45 minutes and the rest frozen within 1 hour&#xD;
      and will be stored at minus 20 degrees celsius until analysis.&#xD;
&#xD;
      OUTCOME MEASUREMENTS&#xD;
&#xD;
      Primary endpoints&#xD;
&#xD;
      •Changes in total, albumin corrected and ionized calcium&#xD;
&#xD;
      Main Secondary endpoints&#xD;
&#xD;
        -  Changes in PTH&#xD;
&#xD;
        -  Changes in 1,25OH2D3&#xD;
&#xD;
        -  Changes in Phosphate&#xD;
&#xD;
        -  Changes in FGF23&#xD;
&#xD;
        -  Changes in Calcitonin&#xD;
&#xD;
        -  Changes in LHCGR in serum&#xD;
&#xD;
        -  Changes in Cortisol&#xD;
&#xD;
        -  Changes in total and free testosterone&#xD;
&#xD;
        -  Changes in total and free estradiol&#xD;
&#xD;
        -  Changes in kidney function (GFR/creatinin)&#xD;
&#xD;
        -  Changes in gonadotropins&#xD;
&#xD;
        -  Changes in 25OHD, 24,25OH2D3&#xD;
&#xD;
        -  Changes in serum concentrations of putative regulators and downstream signals&#xD;
           osteocalcin, osteopontin, RANKL, osteoprotegerin (OPG), alpha Klotho, Sclerostin and&#xD;
           IGF-1.&#xD;
&#xD;
      Temporal changes in serum level of binding proteins. differences for vitamin D binding&#xD;
      protein, albumin and sex hormone binding globulin.&#xD;
&#xD;
      Predefined subgroups orchiectomized men/ bilaterally irradiated testis High versus low&#xD;
      baseline estradiol/testosterone Low/high calcium/PTH baseline&#xD;
&#xD;
      ANALYSIS AND INTERVENTION&#xD;
&#xD;
      Reproductive hormones and growth factors will be analysed at dept. of GR, Rigshospitalet.&#xD;
      Other serum analyses will be analysed at Department of clinical biochemistry, and Aarhus&#xD;
      Kommune Hospital&#xD;
&#xD;
      ETHICS AND SIDE EFFECTS All the patients will have full-filled their investigation, before&#xD;
      they are invited to the study. They will be informed of potential adverse effects, and they&#xD;
      can leave the trial at any point without any consequences. This study poses no additional&#xD;
      risk to the patients except for the blood samples as everything else is according to standard&#xD;
      clinical practice.&#xD;
&#xD;
      PUBLICATION OF RESULTS All results, positive or negative will be submitted to peer reviewed&#xD;
      scientific journals. Data will successively be obtained and transferred to a statistical&#xD;
      database.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 1, 2017</start_date>
  <completion_date type="Actual">October 6, 2020</completion_date>
  <primary_completion_date type="Actual">September 30, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>change in total, albumin corrected or ionized calcium</measure>
    <time_frame>72 and 96 hours after hCG injection</time_frame>
    <description>mmol/l</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PTH</measure>
    <time_frame>72 and 96 hours after hCG injection</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>1,25OH2D3</measure>
    <time_frame>72 and 96 hours after hCG injection</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phosphate</measure>
    <time_frame>72 and 96 hours after hCG injection</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>cortisol</measure>
    <time_frame>72 and 96 hours after hCG injection</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>total and free testosterone</measure>
    <time_frame>72 and 96 hours after hCG injection</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>total and free estradiol</measure>
    <time_frame>72 and 96 hours after hCG injection</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>albumin, Shbg, VDBP</measure>
    <time_frame>72 and 96 hours after hCG injection</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>25OHD or 24,25OH2D3</measure>
    <time_frame>72 and 96 hours after hCG injection</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>bone factors such as CTX, osteocalcin, RANKL, FGF23</measure>
    <time_frame>72 and 96 hours after hCG injection</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>LHCGR</measure>
    <time_frame>72 and 96 hours after hCG injection</time_frame>
    <description>in serum</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>kidney function</measure>
    <time_frame>72 and 96 hours after hCG injection</time_frame>
    <description>eGFR/creatinine</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">242</enrollment>
  <condition>Hypogonadism, Male</condition>
  <arm_group>
    <arm_group_label>hypogondal men</arm_group_label>
    <description>men referred for hCG stimulation test</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>human chorionic gonadotropin</intervention_name>
    <description>5000 IE times one</description>
    <arm_group_label>hypogondal men</arm_group_label>
    <other_name>hCG</other_name>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      serum&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        men with suspected gonadal i suffciency ofter after orchiectomy or bilateral irradiation&#xD;
        due to testis cancer&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        - men aged 18-60 years referred for hCG stimulation test due to previous treatment for&#xD;
        testis cancer&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  high intake calcium&#xD;
&#xD;
          -  know disorders in calcium homeostasis&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <gender_description>referred for hCG stimulation test</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Department of Growth and Reproduction, Rigshospitalet</name>
      <address>
        <city>Copenhagen</city>
        <zip>2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <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>October 2020</verification_date>
  <study_first_submitted>August 15, 2017</study_first_submitted>
  <study_first_submitted_qc>August 15, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 18, 2017</study_first_posted>
  <last_update_submitted>October 6, 2020</last_update_submitted>
  <last_update_submitted_qc>October 6, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 8, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Rigshospitalet, Denmark</investigator_affiliation>
    <investigator_full_name>Martin Blomberg Jensen</investigator_full_name>
    <investigator_title>MD, group leader</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <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>Chorionic Gonadotropin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>share all available data through danish data archive</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_time_frame>2 years after study completion</ipd_time_frame>
  </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/NCT03254641
org study id: H-17004362
nct id: NCT03254641
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
We have in a pilot study found that serum calcium levels change in response to hCG
      stimulation test. We observed that serum calcium level measured at baseline and 72 hours
      after hCG stimulation were different in men with gonadal insufficiency referred for this
      stimulation test. Now we want to investigate a large cohort of men referred for hCG
      stimulation test due to suspected impaired gonadal function.
Introduction:

      hCG signals through the LHCGR receptor and is know to stimulate testosterone production. hCG
      stimulation tests are therefore used to evaulate the capacity of the testis to respond to
      LH/hCG and thereby determine the degree og gonadal insufficiency and need for testosterone
      supplementation. Some groups have found LHCRG in extragondal tissues indicating a direct
      effect of hCG/LH outside the gonads. We noticed that some men with gonadal insuffciency had a
      low calcium level after hCG stimulation test. Now we would like to investigate whether this
      putative effect on calcium homeostasis of hCG is due to a direct effect or an indirect effect
      through testosterone or other sex steroids that also change in response to hCG stimulation.
      Moreover, we would like to clarify whether the chnage in calcium is compensated by classical
      regulators such as PTH, 1,25OH2D3, calcitonin, phosphate, CTX, alkaline phosphatase or other
      factors.

      Aim of study:

      The purpose of this study is to describe changes in calcium and calciotropic hormones after
      hCG stimulation test

      DESIGN This is a prospective observational study

      Patients and methods 100 men referred for hCG stimulation test due to suspected gonadal
      insuffciency age 18-60 years at Department of growth and reproduction, Rigshospitalet

      Exclusion criteria are

      intake of high dose calcium (above 1 mg daily) Known Disorders related to calcium metabolism,
      hypercalcemia, Granulomatous disease such as Wegener, tuberculosis, etc,

      SAMPLE SIZE CALCULATION AND STATISTICS By using a test level of 5% (level of significance),
      power of 80% and at least 100 men completing the trial will enable us to detect a change in
      calcium of 10%, and a change in serum PTH of 30%.

      SCREENING AND TIME COURSE Men referred for hCG stimulation test at ourDepartment will be
      screened for eligibility to the study. Those who meet the criteria for participation will be
      informed, and if they consent allocated to the study.

      Each person will have one blood sampling performed prior to the test and 72 and 96 hours
      after the test.

      Blood samples Venus blood is drawn preoperatively before hCG administration, 72 and 96 hours
      after. Serum will be send for analysis within 45 minutes and the rest frozen within 1 hour
      and will be stored at minus 20 degrees celsius until analysis.

      OUTCOME MEASUREMENTS

      Primary endpoints

      •Changes in total, albumin corrected and ionized calcium

      Main Secondary endpoints

        -  Changes in PTH

        -  Changes in 1,25OH2D3

        -  Changes in Phosphate

        -  Changes in FGF23

        -  Changes in Calcitonin

        -  Changes in LHCGR in serum

        -  Changes in Cortisol

        -  Changes in total and free testosterone

        -  Changes in total and free estradiol

        -  Changes in kidney function (GFR/creatinin)

        -  Changes in gonadotropins

        -  Changes in 25OHD, 24,25OH2D3

        -  Changes in serum concentrations of putative regulators and downstream signals
           osteocalcin, osteopontin, RANKL, osteoprotegerin (OPG), alpha Klotho, Sclerostin and
           IGF-1.

      Temporal changes in serum level of binding proteins. differences for vitamin D binding
      protein, albumin and sex hormone binding globulin.

      Predefined subgroups orchiectomized men/ bilaterally irradiated testis High versus low
      baseline estradiol/testosterone Low/high calcium/PTH baseline

      ANALYSIS AND INTERVENTION

      Reproductive hormones and growth factors will be analysed at dept. of GR, Rigshospitalet.
      Other serum analyses will be analysed at Department of clinical biochemistry, and Aarhus
      Kommune Hospital

      ETHICS AND SIDE EFFECTS All the patients will have full-filled their investigation, before
      they are invited to the study. They will be informed of potential adverse effects, and they
      can leave the trial at any point without any consequences. This study poses no additional
      risk to the patients except for the blood samples as everything else is according to standard
      clinical practice.

      PUBLICATION OF RESULTS All results, positive or negative will be submitted to peer reviewed
      scientific journals. Data will successively be obtained and transferred to a statistical
      database.
observational model: Case-Only
time perspective: Prospective
measure: change in total, albumin corrected or ionized calcium
time frame: 72 and 96 hours after hCG injection
description: mmol/l
measure: PTH
time frame: 72 and 96 hours after hCG injection
measure: 1,25OH2D3
time frame: 72 and 96 hours after hCG injection
measure: Phosphate
time frame: 72 and 96 hours after hCG injection
measure: cortisol
time frame: 72 and 96 hours after hCG injection
measure: total and free testosterone
time frame: 72 and 96 hours after hCG injection
measure: total and free estradiol
time frame: 72 and 96 hours after hCG injection
measure: albumin, Shbg, VDBP
time frame: 72 and 96 hours after hCG injection
measure: 25OHD or 24,25OH2D3
time frame: 72 and 96 hours after hCG injection
measure: bone factors such as CTX, osteocalcin, RANKL, FGF23
time frame: 72 and 96 hours after hCG injection
measure: LHCGR
time frame: 72 and 96 hours after hCG injection
description: in serum
measure: kidney function
time frame: 72 and 96 hours after hCG injection
description: eGFR/creatinine
arm group label: hypogondal men
description: men referred for hCG stimulation test
intervention type: Drug
intervention name: human chorionic gonadotropin
description: 5000 IE times one
arm group label: hypogondal men
other name: hCG
serum
study pop: 
sampling method: Probability Sample
criteria: 
gender: Male
gender based: Yes
gender description: referred for hCG stimulation test
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
facility: 
country: Denmark
responsible party type: Sponsor-Investigator
investigator affiliation: Rigshospitalet, Denmark
investigator full name: Martin Blomberg Jensen
investigator title: MD, group leader
mesh term: Hypogonadism
mesh term: Eunuchism
mesh term: Chorionic Gonadotropin
sharing ipd: Yes
ipd description: share all available data through danish data archive
ipd info type: Study Protocol
ipd time frame: 2 years after study completion