Trial of Testosterone Undecanoate for Optimizing Performance During Military Operations (OPS II)

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

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.

Study Overview

• Status: Completed
• Conditions: Sleep; Exercise; Caloric Restriction
• Intervention / Treatment: Drug: Sesame Oil; Drug: Testosterone Undecanoate

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.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Pennington Biomedical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Pennington Biomedical Research Center
• Collaborators: United States Department of Defense; University of Arkansas; United States Army Research Institute of Environmental Medicine
• Investigators: Principal Investigator: Jennifer C Rood, PhD, Pennington Biomedical Research Center

Publications and helpful links

General Publications

• Varanoske AN, Harris MN, Hebert C, Howard EE, Johannsen NM, Heymsfield SB, Greenway FL, Margolis LM, Lieberman HR, Church DD, Ferrando AA, Rood JC, Pasiakos SM. Effects of testosterone undecanoate on performance during multi-stressor military operations: A trial protocol for the Optimizing Performance for Soldiers II study. Contemp Clin Trials Commun. 2021 Jul 3;23:100819. doi: 10.1016/j.conctc.2021.100819. eCollection 2021 Sep.

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2019
• Primary Completion (Actual): July 8, 2021
• Study Completion (Actual): July 8, 2021

Study Registration Dates

• First Submitted: October 4, 2019
• First Submitted That Met QC Criteria: October 7, 2019
• First Posted (Actual): October 9, 2019

Study Record Updates

• Last Update Posted (Actual): October 7, 2022
• Last Update Submitted That Met QC Criteria: September 12, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: muscle mass; testosterone; anabolism; military operational stress
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Androgens; Anabolic Agents; Testosterone; Methyltestosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate
• Other Study ID Numbers: PBRC 2019-017; W81XWH19C0162 (Other Grant/Funding Number: USA MED RESEARCH ACQ ACTIVITY); W81XWH19D0010 (Other Grant/Funding Number: USA MED RESEARCH ACQ ACTIVITY)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No