Intranasal Delivery of Testosterone and Its Effect on Doping Markers (Intranasal)

• ClinicalTrials.gov Identifier: NCT02611154
• Recruitment Status: Completed
• First Posted: November 20, 2015
• Results First Posted: March 10, 2017
• Last Update Posted: February 11, 2020
• Sponsor: University of Utah
• Collaborators: Sports Medicine Research and Testing Laboratory; Partnership for Clean Competition
• Information provided by (Responsible Party): Stuart Willick, University of Utah

Study Description

Brief Summary:

Hypothesis: Intranasal administration of exogenous testosterone results in a characteristic profile during anti-doping testing, which is different than the profile seen when testosterone is administered into muscle, on skin or under the tongue.

Objective: The investigators aim to characterize the unique steroid doping profile following administration of intranasal testosterone to healthy, active volunteer subjects.

Condition or disease	Intervention/treatment	Phase
Abuse of Anabolic Steroids	Drug: Testosterone	Phase 4

Detailed Description:

Testosterone is a substance commonly abused in the sporting world despite being banned by all American sports leagues, international federations, and the World Anti-Doping Agency. Current methods employed to detect exogenously administered testosterone include direct detection using isotope ratio mass spectrometry (IRMS) and indirect detection using the athlete biological passport (ABP). However, different formulations of testosterone (oral, transdermal, sublingual, etc) are expected to result in characteristic IRMS profiles, affect the ABP readings in unique ways, and differ in their windows of detection. In 2014, a new formulation of testosterone, Natesto, which is administered intranasally, was FDA approved. Though only approved for medical use, it is expected athletes may use this product, and its effect on steroid doping markers has yet to be determined. Characterization of this detection profile is necessary for confirmation of the exact product being administered in an anti-doping setting. In this study, the investigators aim to understand the effects on the steroid doping profile following a single administration of Natesto to healthy, active volunteers. Windows of detection will be determined for the standard dosing of Natesto, and the effects on ABP markers and IRMS profiles will also be established.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Intranasal Delivery of Testosterone and Its Effect on Doping Markers
• Actual Study Start Date: November 18, 2015
• Actual Primary Completion Date: January 19, 2016
• Actual Study Completion Date: January 19, 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Intranasal Testosterone; All participants will be receiving intranasal testosterone and will follow the same study procedures.	Drug: Testosterone; Participants will self-administer 11 mg 3x daily, for 5 consecutive days for 4 weeks.; Other Name: Natesto

Outcome Measures

Primary Outcome Measures :

1. Steroid Levels in Urine Steroid Profile [ Time Frame: 4 weeks of dosing for each participant ]

   Participants were instructed to follow this dosing pattern:

   Begin taking Intranasal Testosterone at Day 1 for 5 consecutive days (Days 1-5), then to take 2 days off (Day 6 and 7) Urine sample at Day 6 Begin taking Intranasal Testosterone at Day 8 for 5 consecutive days (Days 8-12), then to take 3 days off (Day 13, Day 14, Day 15) Urine sample at Day 13 Begin taking Intranasal Testosterone at Day 16 for 5 consecutive days (Days 16-20), then to take 2 days off (Day 21 and 22) Urine sample at Day 21 Begin taking Intranasal Testosterone at Day 23 for 5 consecutive days (Days 23-27 ), then to take 2 days off (Day 28 and 29) Urine sample at Day 28

   The first day of the dosing pattern is considered Day 1 and the last day of the pattern is considered Day 29.

   Samples 4-8 were analyzed between 0 and 24hours post-dose Sample 9 was analyzed 48 hours post-dose Sample 10 was analyzed 72 hours post-dose Sample 11 was analyzed one week post-dose

Secondary Outcome Measures :

1. Number of Participants With Suspicious Steroid Profile in Urine Samples at Baseline [ Time Frame: Day 1, Day 3, Day 5 ]
   Participants were asked to provide 3 urine samples at Day 1, Day 3, Day 5 to measure their baseline urinary steroid marker levels. To accommodate participant schedules, all baseline samples were collected within a two week timeframe. This outcome is measuring if any participants baseline urine samples resulted in a suspicious steroid profile. For this study, "suspicious" is defined as any urine sample resulting in testosterone steroid detection above 200ng/mL.
2. Testosterone Level in Blood as Measured for Safety [ Time Frame: Day 0 and Day 19 ]
   Testosterone level in blood to ensure safety levels of testosterone prior to (Day 0) and after the first two weeks of drug administration (Day 19). Steroid levels below the normal range were considered safe to continue study participation.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 35 Years (Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Males between the ages of 18 and 35 years-old who participate in regular, moderate to high intensity physical activity will be recruited for the study.

Exclusion Criteria:

1. Individuals below the age of 18 or greater than the age of 35 on the day of enrollment
2. 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.
3. Unwilling to provide blood or urine samples
4. Not actively exercising
5. Individuals with any history of cancer, cardiovascular disease, endocrine abnormalities, renal disease, hepatic disease, neurologic disease or any psychiatric history
6. Individuals with a history of nasal disorders, nasal surgeries, sinus surgeries, or sinus disease
7. Individuals that have a baseline hematocrit value above the normal range
8. Individuals that are diabetic or are currently taking a diabetic medication
9. Individuals that are currently using any WADA prohibited substances
10. Individuals that have recently used or currently using anabolic androgenic steroids

Contacts and Locations

Locations

United States, Utah

University of Utah Orthopaedic Center

Salt Lake City, Utah, United States, 84108

Sponsors and Collaborators

University of Utah

Sports Medicine Research and Testing Laboratory

Partnership for Clean Competition

Investigators

• Principal Investigator: Stuart Willick, MD; University of Utah

More Information

Publications:

Saudan C, Baume N, Robinson N, Avois L, Mangin P, Saugy M. Testosterone and doping control. Br J Sports Med. 2006 Jul;40 Suppl 1:i21-4. Review.

Geyer H, Schänzer W, Thevis M. Anabolic agents: recent strategies for their detection and protection from inadvertent doping. Br J Sports Med. 2014 May;48(10):820-6. doi: 10.1136/bjsports-2014-093526. Epub 2014 Mar 14. Review.

Sottas PE, Saugy M, Saudan C. Endogenous steroid profiling in the athlete biological passport. Endocrinol Metab Clin North Am. 2010 Mar;39(1):59-73, viii-ix. doi: 10.1016/j.ecl.2009.11.003.

Vernec AR. The Athlete Biological Passport: an integral element of innovative strategies in antidoping. Br J Sports Med. 2014 May;48(10):817-9. doi: 10.1136/bjsports-2014-093560. Epub 2014 Mar 21.

Jia H, Sullivan CT, McCoy SC, Yarrow JF, Morrow M, Borst SE. Review of health risks of low testosterone and testosterone administration. World J Clin Cases. 2015 Apr 16;3(4):338-44. doi: 10.12998/wjcc.v3.i4.338. Review.

Bassil N, Alkaade S, Morley JE. The benefits and risks of testosterone replacement therapy: a review. Ther Clin Risk Manag. 2009 Jun;5(3):427-48. Epub 2009 Jun 22.

• Responsible Party: Stuart Willick, M.D., University of Utah
• ClinicalTrials.gov Identifier: NCT02611154
• Other Study ID Numbers: 84225
• First Posted: November 20, 2015
• Results First Posted: March 10, 2017
• Last Update Posted: February 11, 2020
• Last Verified: January 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Data will be published in scientific literature without Patient Health Information (PHI) identifying any participant data.

Keywords provided by Stuart Willick, University of Utah:

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

Additional relevant MeSH terms:

Testosterone; Androgens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs