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Intranasal Delivery of Testosterone and Its Effect on Doping Markers

Sponsor
University of Utah (Other)
Overall Status
Completed
CT.gov ID
NCT02611154
Collaborator
Sports Medicine Research and Testing Laboratory (Industry), Partnership for Clean Competition (Other)
5
Enrollment
1
Location
1
Arm
2
Actual Duration (Months)
2.5
Patients Per Site Per Month

Study Details

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
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
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 :
Nov 18, 2015
Actual Primary Completion Date :
Jan 19, 2016
Actual Study Completion Date :
Jan 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 Names:
  • Natesto

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Steroid Levels in Urine Steroid Profile [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 [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 [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

    Criteria

    Ages Eligible for Study:
    18 Years to 35 Years
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    Yes
    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

    Site City State Country Postal Code
    1 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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Stuart Willick, M.D., University of Utah
    ClinicalTrials.gov Identifier:
    NCT02611154
    Other Study ID Numbers:
    • 84225
    First Posted:
    Nov 20, 2015
    Last Update Posted:
    Feb 11, 2020
    Last Verified:
    Jan 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Stuart Willick, M.D., University of Utah
    Healthy Volunteers
    Sports Medicine
    Men's Health
    Athletes
    Anti-Doping
    Additional relevant MeSH terms:
    Testosterone

    Study Results

    Participant Flow

    Recruitment Details Recruitment for this study began in November 2015 and ended December 2015. The final participant was enrolled on 03DEC2015 and completed the study on 19JAN2016.
    Pre-assignment Detail
    Arm/Group Title Intranasal Testosterone
    Arm/Group Description All participants will be receiving intranasal testosterone and will follow the same study procedures. Testosterone: Participants will self-administer 11 mg 3x daily, for 5 consecutive days for 4 weeks.
    Period Title: Overall Study
    STARTED 5
    COMPLETED 5
    NOT COMPLETED 0

    Baseline Characteristics

    Arm/Group Title Intranasal Testosterone
    Arm/Group Description All participants will be receiving intranasal testosterone and will follow the same study procedures. Testosterone: Participants will self-administer 11 mg 3x daily, for 5 consecutive days for 4 weeks.
    Overall Participants 5
    Age (Count of Participants)
    <=18 years
    0
    0%
    Between 18 and 65 years
    5
    100%
    >=65 years
    0
    0%
    Sex/Gender, Customized (participants) [Number]
    Male Participants
    5
    100%
    Region of Enrollment (participants) [Number]
    United States
    5
    100%

    Outcome Measures

    1. Primary Outcome
    Title Steroid Levels in Urine Steroid Profile
    Description 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
    Time Frame 4 weeks of dosing for each participant

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Urine Steroid Profile - Day 6 Urine Steroid Profile - Day 13 Urine Steroid Profile - Day 21 Urine Steroid Profile - Day 28 Urine Steroid Profile - Day 29 Urine Steroid Profile - Day 30 Urine Steroid Profile - Day 35 Urine Steroid Profile - Day 42
    Arm/Group Description Day 6 steroid level in urine. Urine sample analyzed within 24 hours of dosing. Day 13 steroid level in urine. Urine sample analyzed within 24 hours of dosing. Day 21 steroid level in urine. Urine sample analyzed within 24 hours of dosing. Day 28 steroid level in urine. Urine sample analyzed within 24 hours of dosing. Day 29 steroid level in urine. Urine sample analyzed within the 24-48 hour window post-administration. Day 30 steroid level in urine. Urine sample analyzed within the 48-72 hour window post-administration. Urine was collected at Day 35 to identify any suppression of endogenous testosterone production following administration. Urine was collected at Day 42 to identify any suppression of endogenous testosterone production following administration.
    Measure Participants 5 5 5 5 5 5 5 5
    Testosterone
    69.5773456
    (35.54601116)
    138.0291641
    (141.9066157)
    163.117081
    (109.276721)
    107.7160658
    (113.703136)
    14.15587072
    (4.228012086)
    21.42280994
    (14.29364856)
    32.9077285
    (13.76180063)
    28.14492389
    (6.661553442)
    Epitestosterone
    14.54132527
    (7.954646945)
    16.23444899
    (11.98868156)
    10.08654906
    (4.588211806)
    9.736167767
    (4.015340993)
    12.22899541
    (4.434891082)
    16.38534782
    (4.918171284)
    27.76476978
    (16.66310752)
    32.56796986
    (10.94213563)
    Androsterone
    2780.422993
    (1545.144279)
    3147.357191
    (2520.278196)
    3377.718911
    (1511.306185)
    4014.439418
    (4846.667258)
    1098.544542
    (430.6835869)
    1689.228939
    (968.2213645)
    2292.971167
    (853.7596469)
    1561.824479
    (663.1827091)
    Etiocholanolone
    3420.811467
    (2957.358109)
    2984.088377
    (2078.022714)
    3168.249168
    (1630.873996)
    4614.568182
    (7192.193898)
    1154.779419
    (460.2075499)
    1810.282342
    (1552.137347)
    2612.685992
    (2105.416619)
    1281.752255
    (372.3518874)
    5αAdiol
    81.50246345
    (28.87216828)
    70.09892435
    (31.91867777)
    79.92660959
    (19.82671546)
    83.39693284
    (59.00306611)
    37.53345262
    (7.673138406)
    51.7003489
    (22.77519196)
    60.19484767
    (21.91151504)
    56.94343765
    (30.25653073)
    5βAdiol
    323.5235566
    (95.27658018)
    370.2752839
    (244.8399242)
    386.6496467
    (178.3061711)
    369.209311
    (243.4060107)
    145.5896139
    (54.18663296)
    158.5303528
    (90.57253904)
    166.0185686
    (97.42880397)
    85.54384971
    (17.46215146)
    2. Secondary Outcome
    Title Number of Participants With Suspicious Steroid Profile in Urine Samples at Baseline
    Description 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.
    Time Frame Day 1, Day 3, Day 5

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Testosterone Epitestosterone Androsterone Etiocholanolone 5αAdiol 5βAdiol
    Arm/Group Description Testosterone level will be measured in the urine sample. Epitestosterone level will be measured in the urine sample. Androsterone level will be measured in the urine sample. Etiocholanolone level will be measured in the urine sample. 5αAdiol level will be measured in the urine sample. 5βAdiol level will be measured in the urine sample.
    Measure Participants 5 5 5 5 5 5
    Count of Participants [Participants]
    0
    0%
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    3. Secondary Outcome
    Title Testosterone Level in Blood as Measured for Safety
    Description 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.
    Time Frame Day 0 and Day 19

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Serum Testosterone - Day 0 Serum Testosterone - Day 19
    Arm/Group Description Serum Testosterone at Day 0 Serum Testosterone at Day 19
    Measure Participants 5 5
    Mean (Full Range) [ng/mL]
    408.4
    373.4

    Adverse Events

    Time Frame 2 months
    Adverse Event Reporting Description
    Arm/Group Title Intranasal Testosterone
    Arm/Group Description All participants will be receiving intranasal testosterone and will follow the same study procedures. Testosterone: Participants will self-administer 11 mg 3x daily, for 5 consecutive days for 4 weeks.
    All Cause Mortality
    Intranasal Testosterone
    Affected / at Risk (%) # Events
    Total / (NaN)
    Serious Adverse Events
    Intranasal Testosterone
    Affected / at Risk (%) # Events
    Total 0/5 (0%)
    Other (Not Including Serious) Adverse Events
    Intranasal Testosterone
    Affected / at Risk (%) # Events
    Total 0/5 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Geoffry Miller
    Organization Sports Medicine Research & Testing Laboratory
    Phone 801-994-9519
    Email gmiller@smrtl.org
    Responsible Party:
    Stuart Willick, M.D., University of Utah
    ClinicalTrials.gov Identifier:
    NCT02611154
    Other Study ID Numbers:
    • 84225
    First Posted:
    Nov 20, 2015
    Last Update Posted:
    Feb 11, 2020
    Last Verified:
    Jan 1, 2020