NCT06455969

Adaptions and Resiliency to Multi-Stressor OpeRations

Musculoskeletal Resiliency and Adaptation to Sex Steroid Suppression and Replacement During Multi-Stressor Training

• Status: Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 120 (estimated)
• Sponsor: Bradley Nindl · Academic / Other
• Sex: All
• Age: 18 Years – 40 Years
• Healthy volunteers: Accepted

Summary

Non-combat-related muscle, tendon and bone injuries are the most common injuries suffered by military personnel, particularly in new recruits. These injuries impact military readiness and are responsible for roughly 60% of limited duty days, 65% of soldiers who are unable to deploy, and nearly $500 million in medical cost to the government annually in the Army alone. Drug interventions must be studied and developed to prevent these negative outcomes and prepare military personnel for the demands of military service. At the current time, military leadership has identified critical gaps in understanding how to minimize these injuries and train soldiers with drug intervention serving among those gaps. The goal of this study is to determine how a hormonal intervention can change muscle, tendon, and bone function as well as physical and psychological performance in response to mental and physical stress. To do so, we will examine sex hormone (testosterone, estrogen) levels, muscle, tendon, and bone images, blood samples, and physical and mental performance. We will look at things like changes in hormone levels, chemicals released from active skeletal muscles, and your body composition. The results from this study will be used to improve physical readiness training in the military with the goal of reducing injuries.

Detailed description

Suppression of the reproductive hypothalamic-pituitary-gonadal (HPG) axis is a common physiological response to strenuous military training and can be difficult to replicate in simulated environments. Additionally, whether HPG suppression contributes to the physiological changes, performance decrements, and high MSK injury risk associated with multi-stressor military training is unknown. Thus, we will utilize pharmacological inhibition of the HPG axis to test if estrogen and testosterone replacement will mitigate injury risk and performance decrements following military-relevant multi-stressor training. This project aims to deliver a state-of-the-art evaluation of male and female adaptive responses to multi-stressor training and evidence-based guidance for the safe and ethical use of exogenous hormone replacement as a MSK injury mitigation solution during multi-stressor training and operations.

Conditions

• Musculoskeletal Injury
• Hypogonadism

Interventions

Type	Name	Description
DRUG	Goserelin 3.6 MG	Goserelin acetate (Zoladex) is a gonadotropin-releasing hormone agonist (GnRH). GnRH agonists induce a transient increase in sex hormone concentrations, but subsequently inhibit gonadotropin secretion and the production of testosterone in men and estrogen in women. An equilibration period will occur to allow steroid concentrations to reduce.
OTHER	Multi-Stressor Training	A 4-week physical training program that mimics military training.
DRUG	Testosterone gel (AndroGel 5g)	Male subjects will be randomly assigned to receive a topical testosterone gel (5g dose).
DRUG	Testosterone gel (AndroGel 1.25g)	Male subjects will be randomly assigned to receive a topical testosterone gel (1.25g dose).
DRUG	Estradiol / Levonorgestrel Transdermal System [Climara Pro]	Female subjects will be randomly assigned to receive a estrogen/ progesterone patch.
DRUG	Placebo Patch	Female subjects will be randomly assigned to receive a placebo patch identical to the Climara Pro patch.

Timeline

• Start date: 2024-07-15
• Primary completion: 2026-08-01
• Completion: 2026-08-01
• First posted: 2024-06-13
• Last updated: 2025-08-24

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study