Clinical trial NCT03028532: Administration of Clomiphene: Short and Long Term Metabolism in an Anti-Doping Setting
Official title: Administration of Clomiphene: Short and Long Term Metabolism in an Anti-Doping Setting
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Sports Drug Abuse
Abuse of Steroids or Hormones
Keywords: Healthy Volunteers
Sports Medicine
Anti-doping
Athletes
Men's Health
Lead sponsor: University of Utah
Sponsor class: OTHER
Collaborators: name: Sports Medicine Research and Testing Laboratory
name: Partnership for Clean Competition
First posted: 2017-01-23
Enrollment: 12
Sex: MALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: 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

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

- Active males who engage in regular exercise between the ages of 18 and 40 on the day of enrollment

• For this study, regular exercise is defined as: physical activity resulting in an increased heart rate for at least 30 minutes per day, 4-5 days per week.

Exclusion Criteria:

* Individuals outside of the described age range on the day of enrollment
* Individuals who are in a Registered Testing Pool for anti-doping purposes, or individuals who for any reason could be subject to doping control testing
* Individuals who are unwilling or unable to provide blood or urine samples
* Individuals who do not actively exercise
* Individuals with any history of cancer, cardiovascular disease, endocrine abnormalities, infertility, hypoandrogenism, renal disease, hepatic disease, neurologic disease, or any psychiatric history
* Individuals who have previously used anabolic steroids, selective estrogen receptor modulators (SERMs), selective androgen receptor modulators (SARMs), or who are currently using any substances included on the WADA Prohibited List
* History of venous thromboembolic disease (i.e. deep vein thrombosis or pulmonary embolism)
* History of untreated cataracts
* History of intracranial lesions such as pituitary tumors
* Transaminase elevation greater than 3 times the upper limit of normal (ULN)
* Moderate or heavy alcohol intake

Primary outcomes:
measure: The window of detection for the clomiphene parent compound and metabolites following a 30-day administration will be identified.
timeFrame: Day 30 through end of study participation (minimum, Day 72)
Secondary outcomes:
measure: Effect of clomiphene administration on serum LH, FSH, and T levels for potential inclusion into a hematological-based longitudinal steroid profile.
timeFrame: Day 30 through end of study participation (minimum, Day 72)
measure: Effect on current steroidal module of Athlete Biological Passport
timeFrame: Day 30 through end of study participation (minimum, Day 72)
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: Heidi Jo Hansen
state: Utah
Study officials:
affiliation: University of Utah
name: Stuart Willick, MD
role: PRINCIPAL_INVESTIGATOR
References:
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: 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: 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: 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: 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: 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: 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: 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: 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: Miller GD, Moore C, Nair V, Hill B, Willick SE, Rogol AD, Eichner D. Hypothalamic-Pituitary-Testicular Axis Effects and Urinary Detection Following Clomiphene Administration in Males. J Clin Endocrinol Metab. 2019 Mar 1;104(3):906-914. doi: 10.1210/jc.2018-01159.