<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/NCT03028532</url>
  </required_header>
  <id_info>
    <org_study_id>97194</org_study_id>
    <nct_id>NCT03028532</nct_id>
  </id_info>
  <brief_title>Administration of Clomiphene: Short and Long Term Metabolism in an Anti-Doping Setting</brief_title>
  <official_title>Administration of Clomiphene: Short and Long Term Metabolism in an Anti-Doping Setting</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stuart Willick</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Sports Medicine Research and Testing Laboratory</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Partnership for Clean Competition</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Utah</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Clomiphene (Clomid) is a drug FDA approved to treat female infertility, however, it is often&#xD;
      used by men in an off-label setting to both treat male infertility and in a multitude of&#xD;
      sports disciplines to increase performance.&#xD;
&#xD;
      Study Objectives:&#xD;
&#xD;
        -  Determine detection windows for clomiphene and its metabolites in urine following a&#xD;
           medium-term administration&#xD;
&#xD;
        -  Understand the effect of clomiphene administration on luteinizing hormone (LH),&#xD;
           follicle-stimulating hormone (FSH), and serum testosterone (T) concentrations in a&#xD;
           longitudinal manner&#xD;
&#xD;
        -  Identify changes in current steroidal module of Athlete Biological Passport&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Clomiphene, pharmaceutically prepared as clomiphene citrate, is a selective estrogen receptor&#xD;
      modulator (SERM) with a therapeutic indication to treat female infertility. Though&#xD;
      FDA-approved only for use in women, clomiphene is often prescribed off-label to males to&#xD;
      treat male infertility and secondary hypogonadism due to its ability to increase serum&#xD;
      testosterone levels. Numerous clinical studies have documented both the effectiveness for&#xD;
      these indications and safety of clomiphene administration in males. Increasing the&#xD;
      concentration of circulating testosterone can have additional effects, including the&#xD;
      enhancement of performance in sports. As such, clomiphene is already abused by athletes in&#xD;
      several sporting disciplines, including mixed martial arts, cycling, and bodybuilding.&#xD;
      Therefore, clomiphene is a prohibited substance under the World Anti-Doping Agency code .&#xD;
      Though the parent compound and metabolites of clomiphene are directly detectable in routine&#xD;
      anti-doping screening, the urinary detection window and the effect of clomiphene&#xD;
      administration on other anti-doping markers are unknown and thus the foci of this study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 13, 2017</start_date>
  <completion_date type="Actual">October 15, 2018</completion_date>
  <primary_completion_date type="Actual">January 25, 2018</primary_completion_date>
  <phase>Phase 1</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>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The window of detection for the clomiphene parent compound and metabolites following a 30-day administration will be identified.</measure>
    <time_frame>Day 30 through end of study participation (minimum, Day 72)</time_frame>
    <description>◦This will be determined as the amount of time following the final dose (day 30) until clomiphene nor its metabolites are no longer detectable in a urine sample.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Effect of clomiphene administration on serum LH, FSH, and T levels for potential inclusion into a hematological-based longitudinal steroid profile.</measure>
    <time_frame>Day 30 through end of study participation (minimum, Day 72)</time_frame>
    <description>A baseline for LH, FSH, and T will be established using the average of serum concentrations calculated from the pre-administration samples from each subject.The change in serum concentrations following administration will be compared against the baseline values.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect on current steroidal module of Athlete Biological Passport</measure>
    <time_frame>Day 30 through end of study participation (minimum, Day 72)</time_frame>
    <description>◦The steroidal module of the Athlete Biological Passport, a statistical model used to identify doping, will be used for data analysis in this study.As stated in the ABP Operating Guidelines, the steroidal compounds described above are considered for the ABP steroidal module in addition to the following ratios: T/E, A/T, A/Etio, 5aAdiol/5βAdiol, and 5aAdiol/E. Changes in the urinary steroid concentrations and these ratios will be assessed over the course of the study.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Sports Drug Abuse</condition>
  <condition>Abuse of Steroids or Hormones</condition>
  <arm_group>
    <arm_group_label>Clomid</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All participants will be receiving Clomid and will follow the same study procedures.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Clomid</intervention_name>
    <description>Participants will self-administer Clomid (50mg oral tablet) once daily for 30 consecutive days</description>
    <arm_group_label>Clomid</arm_group_label>
    <other_name>Clomiphene</other_name>
    <other_name>Clomifene</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        - Active males who engage in regular exercise between the ages of 18 and 40 on the day of&#xD;
        enrollment&#xD;
&#xD;
        • For this study, regular exercise is defined as: physical activity resulting in an&#xD;
        increased heart rate for at least 30 minutes per day, 4-5 days per week.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Individuals outside of the described age range on the day of enrollment&#xD;
&#xD;
          -  Individuals who are in a Registered Testing Pool for anti-doping purposes, or&#xD;
             individuals who for any reason could be subject to doping control testing&#xD;
&#xD;
          -  Individuals who are unwilling or unable to provide blood or urine samples&#xD;
&#xD;
          -  Individuals who do not actively exercise&#xD;
&#xD;
          -  Individuals with any history of cancer, cardiovascular disease, endocrine&#xD;
             abnormalities, infertility, hypoandrogenism, renal disease, hepatic disease,&#xD;
             neurologic disease, or any psychiatric history&#xD;
&#xD;
          -  Individuals who have previously used anabolic steroids, selective estrogen receptor&#xD;
             modulators (SERMs), selective androgen receptor modulators (SARMs), or who are&#xD;
             currently using any substances included on the WADA Prohibited List&#xD;
&#xD;
          -  History of venous thromboembolic disease (i.e. deep vein thrombosis or pulmonary&#xD;
             embolism)&#xD;
&#xD;
          -  History of untreated cataracts&#xD;
&#xD;
          -  History of intracranial lesions such as pituitary tumors&#xD;
&#xD;
          -  Transaminase elevation greater than 3 times the upper limit of normal (ULN)&#xD;
&#xD;
          -  Moderate or heavy alcohol intake&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Stuart Willick, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Utah</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Heidi Jo Hansen</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84124</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/016131s026lbl.pdf</url>
    <description>Clomid Drug Information</description>
  </link>
  <link>
    <url>http://www.usada.org/testing/results/sanctions/</url>
    <description>USADA Sanctions</description>
  </link>
  <link>
    <url>http://www.evolutionary.org/clomid-clomiphene-citrate</url>
    <description>Clomid Drug Information</description>
  </link>
  <link>
    <url>http://www.mmafighting.com/2016/7/23/12261944/brock-lesnar-tested-positive-for-anti-estrogen-lesnar-jon-jones-won-t</url>
    <description>Clomid Use in MMA</description>
  </link>
  <reference>
    <citation>Guay AT, Jacobson J, Perez JB, Hodge MB, Velasquez E. Clomiphene increases free testosterone levels in men with both secondary hypogonadism and erectile dysfunction: who does and does not benefit? Int J Impot Res. 2003 Jun;15(3):156-65. doi: 10.1038/sj.ijir.3900981.</citation>
    <PMID>12904801</PMID>
  </reference>
  <reference>
    <citation>Katz DJ, Nabulsi O, Tal R, Mulhall JP. Outcomes of clomiphene citrate treatment in young hypogonadal men. BJU Int. 2012 Aug;110(4):573-8. doi: 10.1111/j.1464-410X.2011.10702.x. Epub 2011 Nov 1.</citation>
    <PMID>22044663</PMID>
  </reference>
  <reference>
    <citation>Niederberger C. Re: outcomes of clomiphene citrate treatment in young hypogonadal men. J Urol. 2013 Mar;189(3):1039. doi: 10.1016/j.juro.2012.11.143. Epub 2013 Jan 22. No abstract available.</citation>
    <PMID>23394666</PMID>
  </reference>
  <reference>
    <citation>Taylor F, Levine L. Clomiphene citrate and testosterone gel replacement therapy for male hypogonadism: efficacy and treatment cost. J Sex Med. 2010 Jan;7(1 Pt 1):269-76. doi: 10.1111/j.1743-6109.2009.01454.x. Epub 2009 Aug 17.</citation>
    <PMID>19694928</PMID>
  </reference>
  <reference>
    <citation>Chandrapal JC, Nielson S, Patel DP, Zhang C, Presson AP, Brant WO, Myers JB, Hotaling JM. Characterising the safety of clomiphene citrate in male patients through prostate-specific antigen, haematocrit, and testosterone levels. BJU Int. 2016 Dec;118(6):994-1000. doi: 10.1111/bju.13546. Epub 2016 Jun 24.</citation>
    <PMID>27226135</PMID>
  </reference>
  <reference>
    <citation>Helo S, Mahon J, Ellen J, Wiehle R, Fontenot G, Hsu K, Feustel P, Welliver C, McCullough A. Serum levels of enclomiphene and zuclomiphene in men with hypogonadism on long-term clomiphene citrate treatment. BJU Int. 2017 Jan;119(1):171-176. doi: 10.1111/bju.13625. Epub 2016 Sep 11.</citation>
    <PMID>27511863</PMID>
  </reference>
  <reference>
    <citation>Moskovic DJ, Katz DJ, Akhavan A, Park K, Mulhall JP. Clomiphene citrate is safe and effective for long-term management of hypogonadism. BJU Int. 2012 Nov;110(10):1524-8. doi: 10.1111/j.1464-410X.2012.10968.x. Epub 2012 Mar 28.</citation>
    <PMID>22458540</PMID>
  </reference>
  <reference>
    <citation>Patel DP, Brant WO, Myers JB, Presson AP, Johnstone EB, Dorais JA, Aston KI, Carrell DT, Hotaling JM. The safety and efficacy of clomiphene citrate in hypoandrogenic and subfertile men. Int J Impot Res. 2015 Nov-Dec;27(6):221-4. doi: 10.1038/ijir.2015.21. Epub 2015 Aug 20.</citation>
    <PMID>26289907</PMID>
  </reference>
  <reference>
    <citation>Roth LW, Ryan AR, Meacham RB. Clomiphene citrate in the management of male infertility. Semin Reprod Med. 2013 Jul;31(4):245-50. doi: 10.1055/s-0033-1345271. Epub 2013 Jun 17.</citation>
    <PMID>23775379</PMID>
  </reference>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>January 19, 2017</study_first_submitted>
  <study_first_submitted_qc>January 19, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 23, 2017</study_first_posted>
  <last_update_submitted>January 29, 2020</last_update_submitted>
  <last_update_submitted_qc>January 29, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 30, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Utah</investigator_affiliation>
    <investigator_full_name>Stuart Willick</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Healthy Volunteers</keyword>
  <keyword>Sports Medicine</keyword>
  <keyword>Anti-doping</keyword>
  <keyword>Athletes</keyword>
  <keyword>Men's Health</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Substance-Related Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Clomiphene</mesh_term>
    <mesh_term>Enclomiphene</mesh_term>
    <mesh_term>Zuclomiphene</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/NCT03028532
org study id: 97194
nct id: NCT03028532
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Clomiphene (Clomid) is a drug FDA approved to treat female infertility, however, it is often
      used by men in an off-label setting to both treat male infertility and in a multitude of
      sports disciplines to increase performance.

      Study Objectives:

        -  Determine detection windows for clomiphene and its metabolites in urine following a
           medium-term administration

        -  Understand the effect of clomiphene administration on luteinizing hormone (LH),
           follicle-stimulating hormone (FSH), and serum testosterone (T) concentrations in a
           longitudinal manner

        -  Identify changes in current steroidal module of Athlete Biological Passport
Clomiphene, pharmaceutically prepared as clomiphene citrate, is a selective estrogen receptor
      modulator (SERM) with a therapeutic indication to treat female infertility. Though
      FDA-approved only for use in women, clomiphene is often prescribed off-label to males to
      treat male infertility and secondary hypogonadism due to its ability to increase serum
      testosterone levels. Numerous clinical studies have documented both the effectiveness for
      these indications and safety of clomiphene administration in males. Increasing the
      concentration of circulating testosterone can have additional effects, including the
      enhancement of performance in sports. As such, clomiphene is already abused by athletes in
      several sporting disciplines, including mixed martial arts, cycling, and bodybuilding.
      Therefore, clomiphene is a prohibited substance under the World Anti-Doping Agency code .
      Though the parent compound and metabolites of clomiphene are directly detectable in routine
      anti-doping screening, the urinary detection window and the effect of clomiphene
      administration on other anti-doping markers are unknown and thus the foci of this study.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: The window of detection for the clomiphene parent compound and metabolites following a 30-day administration will be identified.
time frame: Day 30 through end of study participation (minimum, Day 72)
description: ◦This will be determined as the amount of time following the final dose (day 30) until clomiphene nor its metabolites are no longer detectable in a urine sample.
measure: Effect of clomiphene administration on serum LH, FSH, and T levels for potential inclusion into a hematological-based longitudinal steroid profile.
time frame: Day 30 through end of study participation (minimum, Day 72)
description: A baseline for LH, FSH, and T will be established using the average of serum concentrations calculated from the pre-administration samples from each subject.The change in serum concentrations following administration will be compared against the baseline values.
measure: Effect on current steroidal module of Athlete Biological Passport
time frame: Day 30 through end of study participation (minimum, Day 72)
description: ◦The steroidal module of the Athlete Biological Passport, a statistical model used to identify doping, will be used for data analysis in this study.As stated in the ABP Operating Guidelines, the steroidal compounds described above are considered for the ABP steroidal module in addition to the following ratios: T/E, A/T, A/Etio, 5aAdiol/5βAdiol, and 5aAdiol/E. Changes in the urinary steroid concentrations and these ratios will be assessed over the course of the study.
arm group label: Clomid
arm group type: Experimental
description: All participants will be receiving Clomid and will follow the same study procedures.
intervention type: Drug
intervention name: Clomid
description: Participants will self-administer Clomid (50mg oral tablet) once daily for 30 consecutive days
arm group label: Clomid
other name: Clomiphene
other name: Clomifene
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Stuart Willick, MD
role: Principal Investigator
affiliation: University of Utah
facility: 
country: United States
url: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/016131s026lbl.pdf
description: Clomid Drug Information
url: http://www.usada.org/testing/results/sanctions/
description: USADA Sanctions
url: http://www.evolutionary.org/clomid-clomiphene-citrate
description: Clomid Drug Information
url: http://www.mmafighting.com/2016/7/23/12261944/brock-lesnar-tested-positive-for-anti-estrogen-lesnar-jon-jones-won-t
description: Clomid Use in MMA
citation: Guay AT, Jacobson J, Perez JB, Hodge MB, Velasquez E. Clomiphene increases free testosterone levels in men with both secondary hypogonadism and erectile dysfunction: who does and does not benefit? Int J Impot Res. 2003 Jun;15(3):156-65. doi: 10.1038/sj.ijir.3900981.
PMID: 12904801
citation: Katz DJ, Nabulsi O, Tal R, Mulhall JP. Outcomes of clomiphene citrate treatment in young hypogonadal men. BJU Int. 2012 Aug;110(4):573-8. doi: 10.1111/j.1464-410X.2011.10702.x. Epub 2011 Nov 1.
PMID: 22044663
citation: Niederberger C. Re: outcomes of clomiphene citrate treatment in young hypogonadal men. J Urol. 2013 Mar;189(3):1039. doi: 10.1016/j.juro.2012.11.143. Epub 2013 Jan 22. No abstract available.
PMID: 23394666
citation: Taylor F, Levine L. Clomiphene citrate and testosterone gel replacement therapy for male hypogonadism: efficacy and treatment cost. J Sex Med. 2010 Jan;7(1 Pt 1):269-76. doi: 10.1111/j.1743-6109.2009.01454.x. Epub 2009 Aug 17.
PMID: 19694928
citation: Chandrapal JC, Nielson S, Patel DP, Zhang C, Presson AP, Brant WO, Myers JB, Hotaling JM. Characterising the safety of clomiphene citrate in male patients through prostate-specific antigen, haematocrit, and testosterone levels. BJU Int. 2016 Dec;118(6):994-1000. doi: 10.1111/bju.13546. Epub 2016 Jun 24.
PMID: 27226135
citation: Helo S, Mahon J, Ellen J, Wiehle R, Fontenot G, Hsu K, Feustel P, Welliver C, McCullough A. Serum levels of enclomiphene and zuclomiphene in men with hypogonadism on long-term clomiphene citrate treatment. BJU Int. 2017 Jan;119(1):171-176. doi: 10.1111/bju.13625. Epub 2016 Sep 11.
PMID: 27511863
citation: Moskovic DJ, Katz DJ, Akhavan A, Park K, Mulhall JP. Clomiphene citrate is safe and effective for long-term management of hypogonadism. BJU Int. 2012 Nov;110(10):1524-8. doi: 10.1111/j.1464-410X.2012.10968.x. Epub 2012 Mar 28.
PMID: 22458540
citation: Patel DP, Brant WO, Myers JB, Presson AP, Johnstone EB, Dorais JA, Aston KI, Carrell DT, Hotaling JM. The safety and efficacy of clomiphene citrate in hypoandrogenic and subfertile men. Int J Impot Res. 2015 Nov-Dec;27(6):221-4. doi: 10.1038/ijir.2015.21. Epub 2015 Aug 20.
PMID: 26289907
citation: Roth LW, Ryan AR, Meacham RB. Clomiphene citrate in the management of male infertility. Semin Reprod Med. 2013 Jul;31(4):245-50. doi: 10.1055/s-0033-1345271. Epub 2013 Jun 17.
PMID: 23775379
responsible party type: Sponsor-Investigator
investigator affiliation: University of Utah
investigator full name: Stuart Willick
investigator title: Principal Investigator
mesh term: Substance-Related Disorders
mesh term: Clomiphene
mesh term: Enclomiphene
mesh term: Zuclomiphene
sharing ipd: No