Administration of Clomiphene: Short and Long Term Metabolism in an Anti-Doping Setting

Sports Drug Abuse Clinical Trial

Official title:

Administration of Clomiphene: Short and Long Term Metabolism in an Anti-Doping Setting

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03028532
• Other study ID #: 97194
• Status: Completed
• Phase: Phase 1
• Start date: March 13, 2017
• Est. completion date: October 15, 2018

Study information

• Verified date: January 2020
• Source: University of Utah
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: October 15, 2018
• Est. primary completion date: January 25, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Abuse of Steroids or Hormones
• Sports Drug Abuse
• Substance-Related Disorders

Intervention

Drug:
• Clomid
Participants will self-administer Clomid (50mg oral tablet) once daily for 30 consecutive days

Locations

Country	Name	City	State
United States	Heidi Jo Hansen	Salt Lake City	Utah

Sponsors (3)

Lead Sponsor	Collaborator
Stuart Willick	Partnership for Clean Competition, Sports Medicine Research and Testing Laboratory

Country where clinical trial is conducted

United States, 

References & Publications (9)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The window of detection for the clomiphene parent compound and metabolites following a 30-day administration will be identified.	?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.	Day 30 through end of study participation (minimum, Day 72)
Secondary	Effect of clomiphene administration on serum LH, FSH, and T levels for potential inclusion into a hematological-based longitudinal steroid profile.	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.	Day 30 through end of study participation (minimum, Day 72)
Secondary	Effect on current steroidal module of Athlete Biological Passport	?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/5ßAdiol, and 5aAdiol/E. Changes in the urinary steroid concentrations and these ratios will be assessed over the course of the study.	Day 30 through end of study participation (minimum, Day 72)

External Links

•   Clomid Drug Information
•   Clomid Drug Information
•   Clomid Use in MMA
•   USADA Sanctions