Physiological and Psychological Effects of Testosterone During Severe Energy Deficit and Recovery

Phase 4

Completed

Conditions: Caloric Restriction
Exercise

Interventions: Drug: testosterone enanthate
Drug: Sesame Oil

Registration Number: NCT02734238

Lead Sponsor: Pennington Biomedical Research Center

Brief Summary: The objective of this study is to determine whether maintaining a eugonadal state, during severe, sustained energy deficit, attenuates physiological decrements, particularly the loss of lean body mass.

Detailed Description: This study will enroll up to 60 physically active men in a 3-phase randomized, placebo-controlled trial. After completing a 14-day (free-living, phase 1), energy-adequate, diet-acclimation phase (protein, 1.6 g∙kg-1∙d-1; fat 30% total energy intake, with remaining energy derived from carbohydrate), participants will be randomized to one of two experimental groups and undergo a 28-day (live-in, phase 2), 55% energy deficit phase: energy deficit alone (DEF) or energy deficit + exogenous testosterone (DEF+TEST). Recovery (free-living, phase 3) will be assessed after completing phase 2 to determine when body mass has been recovered within ± 2.5% of initial body mass (duration will vary, 42-day maximum for phase 3). This study will delineate the contribution of testosterone declines from the physical and mental demands encountered by Warfighters during military training and combat operations on complex markers of physiological and psychological status, addressing a direct, consistently observed, gap in knowledge.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 53

Inclusion Criteria

Physically active (at least 2 days per week aerobic and/or resistance exercise)
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
- At the discretion of the study physician, wash-out period for medications, supplements, and over-the-counter medications is ≥ 1 to 4 weeks
- Wash-out period for caffeine and alcohol is ≥ 7 days
Willing to live on the Pennington Biomedical Research Center inpatient unit for 28 consecutive days
Willing to have a urine drug screening
Meets age-specific U.S. 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, total testosterone (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
Any use of antibiotics, except topical antibiotics, within 3 months of study participation
Colonoscopy within 3 months of study participation
Chronic use of laxatives, stool softeners, antacids, or anti-diarrheal medications (≥ once a week)
History of gastrointestinal disease (e.g., celiac, irritable bowel syndrome, colitis, Crohn's disease)
Restrained eater (the Three-Factor Eating Questionnaire) as assessed by the study's psychological and behavioral assessment staff
Adults unable to consent
Women
Prisoners
Metal implants, claustrophobia, head size incompatible with MRI equipment, etc.
Sedentary or engages in <2 days of physical activity per week (aerobic and/or resistance training)
Exceeds age-specific U.S. 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
Findings of lab results of prostate-specific antigen > 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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Energy Deficit + Testosterone	testosterone enanthate	Participants randomly assigned to the intervention condition will be subject to exercise-induced energy expenditure resulting in a 55% energy deficit and will be administered testosterone enanthate injections during phase 2 of the trial.
Energy Deficit	Sesame Oil	Participants randomly assigned to the control condition will be subject to exercise-induced energy expenditure resulting in a 55% energy deficit and will be administered sesame oil placebo injections during phase 2 of the trial.

Primary Outcome Measures

Name	Time	Method
Body Composition at the End of Each Study Phase	end of each study phase: Day 11 for Phase 1, Day 39 for Phase 2, up to Day 85 for Phase 3	Height was measured using a stadiometer. Weight was measured using a calibrated digital scale. Body composition was determined using dual-energy X-ray absorptiometry. These data were used to calculate fat-free body mass, fat mass, and total body tissue mass.

Secondary Outcome Measures