Caloric Restriction, Exercise, Sleep
Conditions
Keywords
testosterone, anabolism, muscle mass, military operational stress
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.
Interventions
DRUGTestosterone Undecanoate
single intramuscular injection of 750 mg testosterone undecanoate
DRUGSesame Oil
single intramuscular injection of 750 mg sesame oil solution
Sponsors
United States Army Research Institute of Environmental Medicine
United States Department of Defense
University of Arkansas
Pennington Biomedical Research Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Testosterone single intramuscular injection of 750 mg testosterone undecanoate on Day 8
Testosterone Undecanoate: single intramuscular injection of 750 mg testosterone undecanoate | 16 |
| Placebo single intramuscular injection of 750 mg sesame oil solution on Day 8
Sesame Oil: single intramuscular injection of 750 mg sesame oil solution | 18 |
| Total | 34 |
Baseline characteristics
| Characteristic | Testosterone | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 26.9 years STANDARD_DEVIATION 4.4 | 26.2 years STANDARD_DEVIATION 4.5 | 26.5 years STANDARD_DEVIATION 4.4 |
| BMI | 24.3 kg/m^2 STANDARD_DEVIATION 3.8 | 24.9 kg/m^2 STANDARD_DEVIATION 2.7 | 24.6 kg/m^2 STANDARD_DEVIATION 3.2 |
| Body Mass | 76.5 kg STANDARD_DEVIATION 14.7 | 77.5 kg STANDARD_DEVIATION 10.2 | 77.1 kg STANDARD_DEVIATION 12.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 2 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 16 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height | 177.1 cm STANDARD_DEVIATION 8.1 | 176.3 cm STANDARD_DEVIATION 5.3 | 176.7 cm STANDARD_DEVIATION 6.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 5 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 11 Participants | 12 Participants | 23 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 16 Participants | 18 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 18 |
| other Total, other adverse events | 15 / 16 | 16 / 18 |
| serious Total, serious adverse events | 0 / 16 | 0 / 18 |
Outcome results
Primary
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.
Time frame: Day 5 (Phase 1), Day 26 (Phase 2), Day 47 (Phase 3)
Population: 2 participants in the placebo group dropped out of the study during Phase 2
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Testosterone | Load Carriage Time | 2.5 mile time, Phase 1 | 45.21 min | Standard Error 2.01 |
| Testosterone | Load Carriage Time | 2.5 mile time, Phase 2 | 50.95 min | Standard Error 2.01 |
| Testosterone | Load Carriage Time | 2.5 mile time, Phase 3 | 44.31 min | Standard Error 2.07 |
| Placebo | Load Carriage Time | 2.5 mile time, Phase 1 | 41.58 min | Standard Error 1.94 |
| Placebo | Load Carriage Time | 2.5 mile time, Phase 2 | 47.15 min | Standard Error 1.99 |
| Placebo | Load Carriage Time | 2.5 mile time, Phase 3 | 39.34 min | Standard Error 2.12 |
Primary
Peak Aerobic Capacity
Peak aerobic capacity was measured via treadmill VO2peak near the end of each study phase.
Time frame: Day 4 (Phase 1), Day 25 (Phase 2), Day 46 (Phase 3)
Population: 2 participants in the placebo group dropped out of the study during Phase 2
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Testosterone | Peak Aerobic Capacity | VO2peak, absolute, Phase 1 | 3.22 L/min | Standard Error 0.15 |
| Testosterone | Peak Aerobic Capacity | VO2peak, absolute, Phase 2 | 3.13 L/min | Standard Error 0.15 |
| Testosterone | Peak Aerobic Capacity | VO2peak, absolute, Phase 3 | 3.29 L/min | Standard Error 0.15 |
| Placebo | Peak Aerobic Capacity | VO2peak, absolute, Phase 1 | 3.28 L/min | Standard Error 0.14 |
| Placebo | Peak Aerobic Capacity | VO2peak, absolute, Phase 2 | 3.20 L/min | Standard Error 0.14 |
| Placebo | Peak Aerobic Capacity | VO2peak, absolute, Phase 3 | 3.44 L/min | Standard Error 0.14 |
Primary
Total Mass Lifted
A 3-repetition maximum deadlift assessed muscular strength, endurance, and explosive power near the end of each study phase.
Time frame: Day 4 (Phase 1), Day 25 (Phase 2), Day 46 (Phase 3)
Population: 2 participants in the placebo group dropped out of the study during Phase 2
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Testosterone | Total Mass Lifted | Total Mass Lifted, Phase 1 | 127.4 kg | Standard Error 7.4 |
| Testosterone | Total Mass Lifted | Total Mass Lifted, Phase 2 | 122.7 kg | Standard Error 7.4 |
| Testosterone | Total Mass Lifted | Total Mass Lifted, Phase 3 | 126.7 kg | Standard Error 7.7 |
| Placebo | Total Mass Lifted | Total Mass Lifted, Phase 1 | 127.9 kg | Standard Error 7 |
| Placebo | Total Mass Lifted | Total Mass Lifted, Phase 2 | 119.0 kg | Standard Error 7.2 |
| Placebo | Total Mass Lifted | Total Mass Lifted, Phase 3 | 129.8 kg | Standard Error 7.2 |
Primary
Vertical Jump Height
Lower-body peak power was assessed near the end of each phase using a vertical jump test.
Time frame: Day 4 (Phase 1), Day 25 (Phase 2), Day 46 (Phase 3)
Population: 2 participants in the placebo group dropped out of the study during Phase 2
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Testosterone | Vertical Jump Height | Vertical Jump Height, Phase 1 | 54.5 cm | Standard Error 2.5 |
| Testosterone | Vertical Jump Height | Vertical Jump Height, Phase 2 | 49.1 cm | Standard Error 2.5 |
| Testosterone | Vertical Jump Height | Vertical Jump Height, Phase 3 | 54.0 cm | Standard Error 2.5 |
| Placebo | Vertical Jump Height | Vertical Jump Height, Phase 1 | 53.6 cm | Standard Error 2.4 |
| Placebo | Vertical Jump Height | Vertical Jump Height, Phase 2 | 50.0 cm | Standard Error 2.5 |
| Placebo | Vertical Jump Height | Vertical Jump Height, Phase 3 | 50.5 cm | Standard Error 2.5 |
Primary
Wingate Peak Power
Anaerobic capacity was assessed using a Wingate anaerobic cycle test near the end of each study phase.
Time frame: Day 4 (Phase 1), Day 25 (Phase 2), Day 46 (Phase 3)
Population: 2 participants in the placebo group dropped out of the study during Phase 2
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Testosterone | Wingate Peak Power | Wingate peak power, absolute, Phase 1 | 879.4 W | Standard Error 49.6 |
| Testosterone | Wingate Peak Power | Wingate peak power, absolute, Phase 2 | 753.8 W | Standard Error 49.6 |
| Testosterone | Wingate Peak Power | Wingate peak power, absolute, Phase 3 | 821.8 W | Standard Error 49.6 |
| Placebo | Wingate Peak Power | Wingate peak power, absolute, Phase 1 | 837.8 W | Standard Error 49.6 |
| Placebo | Wingate Peak Power | Wingate peak power, absolute, Phase 2 | 736.0 W | Standard Error 49.6 |
| Placebo | Wingate Peak Power | Wingate peak power, absolute, Phase 3 | 790.8 W | Standard Error 49.6 |
Secondary
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.
Time frame: Day 7 (Phase 1), Day 28 (Phase 2), Day 49 (Phase 3)
Population: 2 participants in the placebo group dropped out of the study during Phase 2
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Testosterone | Body Composition | Fat-free Mass at end of Phase 1 | 59.2 kg | Standard Error 2 |
| Testosterone | Body Composition | Fat-free Mass at end of Phase 2 | 59.6 kg | Standard Error 2 |
| Testosterone | Body Composition | Fat-free Mass at end of Phase 3 | 59.5 kg | Standard Error 2 |
| Testosterone | Body Composition | Fat Mass at end of Phase 1 | 17.3 kg | Standard Error 1.5 |
| Testosterone | Body Composition | Fat Mass at end of Phase 2 | 13.0 kg | Standard Error 1.5 |
| Testosterone | Body Composition | Fat Mass at end of Phase 3 | 15.1 kg | Standard Error 1.5 |
| Placebo | Body Composition | Fat Mass at end of Phase 2 | 14.4 kg | Standard Error 1.6 |
| Placebo | Body Composition | Fat-free Mass at end of Phase 1 | 59.8 kg | Standard Error 2.1 |
| Placebo | Body Composition | Fat Mass at end of Phase 1 | 17.5 kg | Standard Error 1.6 |
| Placebo | Body Composition | Fat-free Mass at end of Phase 2 | 57.9 kg | Standard Error 2.1 |
| Placebo | Body Composition | Fat Mass at end of Phase 3 | 15.5 kg | Standard Error 1.6 |
| Placebo | Body Composition | Fat-free Mass at end of Phase 3 | 59.6 kg | Standard Error 2.1 |