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

Sponsor

Stuart Willick (Other)

Overall Status

Completed

CT.gov ID

NCT03028532

Collaborator

Sports Medicine Research and Testing Laboratory (Industry), Partnership for Clean Competition (Other)

Enrollment

Location

Arm

19.1

Actual Duration (Months)

0.6

Patients Per Site Per Month

Study Details

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

Condition or Disease	Intervention/Treatment	Phase
Sports Drug Abuse Abuse of Steroids or Hormones	Drug: Clomid	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

12 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

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

Actual Study Start Date :

Mar 13, 2017

Actual Primary Completion Date :

Jan 25, 2018

Actual Study Completion Date :

Oct 15, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Clomid All participants will be receiving Clomid and will follow the same study procedures.	Drug: Clomid Participants will self-administer Clomid (50mg oral tablet) once daily for 30 consecutive days Other Names: Clomiphene Clomifene

Arm

Intervention/Treatment

Experimental: Clomid

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

Drug: Clomid

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

Other Names:

Clomiphene

Clomifene

Outcome Measures

Primary Outcome Measures

The window of detection for the clomiphene parent compound and metabolites following a 30-day administration will be identified. [Day 30 through end of study participation (minimum, Day 72)]
◦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. [Day 30 through end of study participation (minimum, Day 72)]
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 [Day 30 through end of study participation (minimum, Day 72)]
◦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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 40 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

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