Trial of Testosterone Undecanoate for Optimizing Performance During Military Operations

Phase 4

Completed

Brief Summary: The objective of this study is to determine the effects of a single dose of testosterone undecanoate during and in recovery from simulated operational stress.

Detailed Description: This is a double-blind, randomized, placebo controlled trial in 32 physically active men exposed to 20 complete days (days 8-27) of simulated operational stress followed by 20 complete days of recovery (days 29-48). After completing baseline testing (Phase 1), participants will be randomized to receive either a single intramuscular injection of testosterone undecanoate or an isovolumetric placebo (Day 8). The 20-day simulated operational stress (Phase 2) will be highly controlled (live-in study) and consist of 4 successive cycles of undulating stress, starting with 2 consecutive days of low stress followed by 3 consecutive days of high stress. Low- and high-stress days will result from low and high militarily-relevant exercise-induced energy expenditures, adequate and restricted sleep (8 hours vs. 4 hours daily), and diet restriction to produce energy deficits. After completing Phase 2, participants will be released to resume their habitual physical activity routines and will be provided a controlled diet to consume (Phase 3), to assess recovery from sustained, severe operational stress.

Recruitment & Eligibility

Inclusion Criteria

Men aged 18-35 years
Ability to understand verbal or written instructions/testing materials in English
Physically active (as determined by accelerometry and review of a physical activity log)
Not taking any prescription medications and/or willing to refrain from all medication use prior to and throughout the entire study period, unless provided/approved by the study physician
Willing to refrain from alcohol, smoking, e-cigarettes or use of any nicotine product, caffeine, and dietary supplement use throughout the entire study period
Willing to live on the Pennington Biomedical Research Center inpatient unit for 20 consecutive days
Meets age-specific US Army body composition standards according to Army Regulation 600-9, which includes estimates of percent body fat based on height, weight, and circumference measures (neck and waist)
Total testosterone concentration is within the normal physiological range (300-1,000 ng/dL)

Exclusion Criteria

Musculoskeletal injuries that compromise exercise capability
Diagnosed cardiometabolic disorders (i.e., hypertension, hyperlipidemia, kidney disease, diabetes, etc.)
Allergies or intolerance to foods, vegetarian practices, or history of complications with lidocaine
Anabolic steroid, human growth hormone, or nutritional testosterone precursor-like supplement use within the past 6 months
Will not refrain from smoking (any nicotine product), alcohol, caffeine, or any other dietary supplement during the study
Adults unable to consent
Women
Prisoners
Sedentary or engages in insufficient quantities of physical activity per week (aerobic and/or resistance training as determined by accelerometry and review of a physical activity log)
Exceeds age-specific US Army body composition standards according to Army Regulation 600-9
Previous history of kidney stones unless otherwise approved by the medical investigator
Systolic blood pressure > 150 or diastolic blood pressure > 95 mmHg
Previous history of breast or prostate cancer
Previous history of Chronic Obstructive Pulmonary Disease or Obstructive Sleep Apnea
Prostate-Specific Antigen (PSA) > 3ng/ml, Hematocrit > 50%, or positive urine drug screening
Based on the investigative team's clinical judgment, a subject may not be appropriate for participation in the study

Arm && Interventions

Group	Intervention	Description
Placebo	Sesame Oil	single intramuscular injection of 750 mg sesame oil solution on Day 8
Testosterone	Testosterone Undecanoate	single intramuscular injection of 750 mg testosterone undecanoate on Day 8

Primary Outcome Measures

Name	Time	Method
Load Carriage Time	Day 5 (Phase 1), Day 26 (Phase 2), Day 47 (Phase 3)	A load carriage time trial (a militarily relevant aerobic performance assessment) was conducted near the end of each study phase to assess aerobic performance.
Vertical Jump Height	Day 4 (Phase 1), Day 25 (Phase 2), Day 46 (Phase 3)	Lower-body peak power was assessed near the end of each phase using a vertical jump test.
Total Mass Lifted	Day 4 (Phase 1), Day 25 (Phase 2), Day 46 (Phase 3)	A 3-repetition maximum deadlift assessed muscular strength, endurance, and explosive power near the end of each study phase.
Wingate Peak Power	Day 4 (Phase 1), Day 25 (Phase 2), Day 46 (Phase 3)	Anaerobic capacity was assessed using a Wingate anaerobic cycle test near the end of each study phase.
Peak Aerobic Capacity	Day 4 (Phase 1), Day 25 (Phase 2), Day 46 (Phase 3)	Peak aerobic capacity was measured via treadmill VO2peak near the end of each study phase.

Secondary Outcome Measures

Name	Time	Method
Body Composition	Day 7 (Phase 1), Day 28 (Phase 2), Day 49 (Phase 3)	A four-compartment (4C) model factoring in body mass, body volume, total body water, and bone mineral content was used to calculate fat-free body mass and fat mass at the end of each study phase.