Sports Drug AbusePhase 1NCT03028532
Administration of Clomiphene: Short and Long Term Metabolism in an Anti-Doping Setting
A Phase 1 study testing Clomid in people with Sports Drug Abuse and Abuse of Steroids or Hormones, run by Stuart Willick at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 40 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Sports Drug Abuse, Abuse of Steroids or Hormones
- What is being tested?
- Clomid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Mar 2017to 15 Oct 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
Read the 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.
- Conditions
- Sports Drug Abuse, Abuse of Steroids or Hormones
- Being tested
- Clomid
- Keywords
- Healthy Volunteers, Sports Medicine, Anti-doping, Athletes, Men's Health
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClomidDrug
Also called Clomiphene, Clomifene
Participants will self-administer Clomid (50mg oral tablet) once daily for 30 consecutive days
| Study group | Role | What they receive |
|---|---|---|
| Clomid | Experimental | All participants will be receiving Clomid and will follow the same study procedures. Receives: Drug: Clomid |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
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.
Measured: Day 30 through end of study participation (minimum, Day 72)
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.
Measured: Day 30 through end of study participation (minimum, Day 72)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2017 (estimated)
- Study start13 Mar 2017
- Primary completion25 Jan 2018
- Study completion15 Oct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Sports Drug AbuseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stuart Willick
- Sponsor type
- University, hospital or other
- Collaborators
- Sports Medicine Research and Testing Laboratory, Partnership for Clean Competition
- Responsible party
- Sponsor-investigator, Stuart Willick, University of Utah
- Investigators
- Stuart Willick, MD, Principal investigator, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03028532
- Sponsor's protocol ID
- 97194
- Status last verified
- Jan 2020
- First submitted
- 19 Jan 2017
- Last updated
- 30 Jan 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 12904801Katz 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.
PubMed 22044663Niederberger 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.
PubMed 23394666Taylor 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.
PubMed 19694928Chandrapal 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.
PubMed 27226135Helo 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.
PubMed 27511863Moskovic 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.
PubMed 22458540Patel 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.
PubMed 26289907Roth 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.
PubMed 23775379Miller 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.
PubMed 30295816
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Administration of Clomiphene: Short and Long Term Metabolism in an Anti-Doping Setting
- ClinicalTrials.gov ID
- NCT03028532
- Acronym / sponsor ID
- 97194
- Conditions
- Sports Drug Abuse, Abuse of Steroids or Hormones
- Keywords
- Healthy Volunteers, Sports Medicine, Anti-doping, Athletes, Men's Health
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Stuart WillickUniversity, hospital or other
- Collaborators
- Sports Medicine Research and Testing Laboratory, Partnership for Clean Competition
- Study start
- 13 Mar 2017 (actual)
- Primary completion
- 25 Jan 2018 (actual)
- Study completion
- 15 Oct 2018 (actual)
- First posted
- 23 Jan 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Clomid | Experimental | Drug: ClomidAll participants will be receiving Clomid and will follow the same study procedures. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ClomidAlso: Clomiphene, ClomifeneParticipants will self-administer Clomid (50mg oral tablet) once daily for 30 consecutive days | Drug | Clomid |
Primary outcome
The window of detection for the clomiphene parent compound and metabolites following a 30-day administration will be identified.
Time frame: 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.
2 secondary outcomes
Effect of clomiphene administration on serum LH, FSH, and T levels for potential inclusion into a hematological-based longitudinal steroid profile.
Time frame: Day 30 through end of study participation (minimum, Day 72)
Effect on current steroidal module of Athlete Biological Passport
Time frame: Day 30 through end of study participation (minimum, Day 72)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2020.
- Background: PubMed 12904801Guay 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.
- Background: PubMed 22044663Katz 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.
- Background: PubMed 23394666Niederberger 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.
- Background: PubMed 19694928Taylor 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.
- Background: PubMed 27226135Chandrapal 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.
- Background: PubMed 27511863Helo 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.
- Background: PubMed 22458540Moskovic 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.
- Background: PubMed 26289907Patel 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.
- Background: PubMed 23775379Roth 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.
- Derived from this study: PubMed 30295816Miller 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.
- Clomid Drug InformationLink provided by the sponsor.
- USADA SanctionsLink provided by the sponsor.
- Clomid Drug InformationLink provided by the sponsor.
- Clomid Use in MMALink provided by the sponsor.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stuart Willick, MD principal investigator
University of Utah
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Clomid in people with Sports Drug Abuse and Abuse of Steroids or Hormones, run by Stuart Willick at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The window of detection for the clomiphene parent compound and metabolites following a 30-day administration will be identified. (time frame: Day 30 through end of study participation (minimum, Day 72)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03028532, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2020.