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

Primary Purpose

Sports Drug Abuse, Abuse of Steroids or Hormones

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Clomid

About this trial

This is an interventional basic science trial for Sports Drug Abuse focused on measuring Healthy Volunteers, Sports Medicine, Anti-doping, Athletes, Men's Health

Eligibility Criteria

18 Years - 40 Years (Adult)MaleAccepts Healthy Volunteers

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

Sites / Locations

Heidi Jo Hansen

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Clomid

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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/5βAdiol, and 5aAdiol/E. Changes in the urinary steroid concentrations and these ratios will be assessed over the course of the study.

Full Information

NCT ID

NCT03028532

First Posted

January 19, 2017

Last Updated

January 29, 2020

Sponsor

Stuart Willick

Collaborators

Sports Medicine Research and Testing Laboratory, Partnership for Clean Competition

1. Study Identification

Unique Protocol Identification Number

NCT03028532

Brief Title

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

2. Study Status

Record Verification Date

January 2020

Overall Recruitment Status

Completed

Study Start Date

March 13, 2017 (Actual)

Primary Completion Date

January 25, 2018 (Actual)

Study Completion Date

October 15, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Stuart Willick

Collaborators

Sports Medicine Research and Testing Laboratory, Partnership for Clean Competition

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Sports Drug Abuse, Abuse of Steroids or Hormones

Keywords

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

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

12 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Clomid

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Clomid

Other Intervention Name(s)

Clomiphene, Clomifene

Intervention Description

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

Primary Outcome Measure Information:

Title

The window of detection for the clomiphene parent compound and metabolites following a 30-day administration will be identified.

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.

Time Frame

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

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

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

Title

Effect on current steroidal module of Athlete Biological Passport

Description

Time Frame

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

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

40 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Stuart Willick, MD

Organizational Affiliation

University of Utah

Official's Role

Principal Investigator

Facility Information:

Facility Name

Heidi Jo Hansen

City

Salt Lake City

State/Province

Utah

ZIP/Postal Code

84124

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

12904801

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.

Results Reference

background

PubMed Identifier

22044663

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.

Results Reference

background

PubMed Identifier

23394666

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.

Results Reference

background

PubMed Identifier

19694928

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.

Results Reference

background

PubMed Identifier

27226135

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.

Results Reference

background

PubMed Identifier

27511863

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.

Results Reference

background

PubMed Identifier

22458540

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.

Results Reference

background

PubMed Identifier

26289907

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.

Results Reference

background

PubMed Identifier

23775379

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.

Results Reference

background

PubMed Identifier

30295816

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.

Results Reference

derived

Links:

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

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

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