Trial of Testosterone Undecanoate for Optimizing Performance During Military Operations

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Randomized, Double-blind, Placebo Controlled Trial of Testosterone Undecanoate for Optimizing Physical and Cognitive Performance During Military Operations (OPS II)

Conditions
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Caloric Restriction, Exercise, Sleep

Intervention / Treatment
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* Drug: Testosterone Undecanoate
* Drug: Sesame Oil


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>single intramuscular injection of 750 mg sesame oil solution on Day 8 | Drug: Sesame Oil<br>* single intramuscular injection of 750 mg sesame oil solution<br>|
| Experimental: Testosterone<br>single intramuscular injection of 750 mg testosterone undecanoate on Day 8 | Drug: Testosterone Undecanoate<br>* single intramuscular injection of 750 mg testosterone undecanoate<br>* Other names: Aveed;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body Composition | 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. | Day 7 (Phase 1), Day 28 (Phase 2), Day 49 (Phase 3) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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testosterone, anabolism, muscle mass, military operational stress