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

NCT03028532 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 97194
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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

Conditions

Sports Drug Abuse; Abuse of Steroids or Hormones

Keywords

Healthy Volunteers; Sports Medicine; Anti-doping; Athletes; Men's Health

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Effect of clomiphene administration on serum LH, FSH, and T levels for potential inclusion into a hematological-based longitudinal steroid profile.

  Day 30 through end of study participation (minimum, Day 72)

• Effect on current steroidal module of Athlete Biological Passport

  Day 30 through end of study participation (minimum, Day 72)

Study Arms (1)

Clomid

EXPERIMENTAL

All participants will be receiving Clomid and will follow the same study procedures.

Drug: Clomid

Interventions

Clomid DRUG

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

Also known as: Clomiphene, Clomifene

Clomid

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• \- 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Stuart Willick: lead
• Sports Medicine Research and Testing Laboratory: collaborator
• Partnership for Clean Competition: collaborator

Study Sites (1)

Heidi Jo Hansen

Salt Lake City, Utah, 84124, United States

Location

Related Publications (10)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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.

  PMID: 30295816 DERIVED

Related Links

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

MeSH Terms

Interventions

Clomiphene

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Stuart Willick, MD

  University of Utah

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 19, 2017
• First Posted: January 23, 2017
• Study Start: March 13, 2017
• Primary Completion: January 25, 2018
• Study Completion: October 15, 2018
• Last Updated: January 30, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)