Adaptions and Resiliency to Multi-Stressor OpeRations

NCT06455969 | Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: STUDY23090134
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hormonal Contraception; Musculoskeletal Injury; Hypogonadism

Keywords

Military; Multi-stressor Training; Tendon; Muscle; Bone

Outcome Measures

Primary Outcomes (11)

• Biomechanical: Tendon Cross-Sectional Area, change from baseline and throughout training, mean

  Through study completion, an average of 8 weeks

• Biomechanical: Tendon Shear Wave Elastography, change from baseline and throughout training, mean

  Through study completion, an average of 8 weeks

• Biomechanical: Tendon Thickness, change from baseline and throughout training, mean

  Through study completion, an average of 8 weeks

• Biomechanical: Quadriceps Muscle Cross-sectional Area, change from baseline and throughout training, mean

  Through study completion, an average of 8 weeks

• Biomechanical: Quadriceps Muscle Echointensity, change from baseline and throughout training, mean

  Through study completion, an average of 8 weeks

• Body composition: Lean mass, change from baseline, mean

  Through study completion, an average of 8 weeks

• Body Composition: Fat mass, change from baseline, mean

  Through study completion, an average of 8 weeks

• Body Composition: Body mass, change from baseline and throughout training, mean

  Through study completion, an average of 8 weeks

• Body Composition: Body Fat Percentage, change from baseline, mean

  Through study completion, an average of 8 weeks

• Biochemical: Bone turnover markers (CTx + P1NP), change from baseline, mean

  Through study completion, an average of 8 weeks

• Biochemical: Sex steroid hormones (Testosterone, Sex Hormone Binding Globulin, Estradiol), change from baseline and throughout training, mean

  Through study completion, an average of 8 weeks

Secondary Outcomes (4)

• Bone microarchitecture: High Resolution- peripheral Computed Tomography, change from baseline, mean

  Through study completion, an average of 8 weeks

• Biochemical: Cell culture, extracellular vesicles, micro- RNAs, change from baseline and throughout study, mean

  Through study completion, an average of 8 weeks

• Biochemical: Measures of inflammation (IL6, IL-1B, TNFa, CRP), change from baseline and throughout study, mean

  Through study completion, an average of 8 weeks

• Biochemical: Measures of anabolism (Growth Hormone, Insulin-like growth factor-1), change from baseline and throughout study, mean

  Through study completion, an average of 8 weeks

Study Arms (5)

CONTROL (men + women)

NO INTERVENTION

The control group will maintain their habitual exercise, diet, and sleep patterns, all of which will be monitored throughout the study.

STRESS (men + women): Multi-Stressor Training

ACTIVE COMPARATOR

Research volunteers will be randomized into the stress exposure group (STRESS) will undergo a 4-week exercise training program consisting of 5 consecutive days of strenuous physical training followed by 2 days of recovery (energy balance, no structured exercise). The exercise training program will consist of military-relevant physical training exercises (e.g., load carriage, aerobic and resistance exercises) that progressively increase in duration and intensity to increase exercise energy expenditure. Participants will perform multiple exercises per day using a variety of endurance and muscle loading modalities designed to mimic movements typically observed during real-life military operations.

Other: Multi-Stressor Training

SUPPRESS (men): Multi-Stressor Training + Zoladex + AndroGel 1.25g

EXPERIMENTAL

In addition to participating in the multi-stressor training program, male participants randomized to the GnRH suppressed (SUPPRESS) group will be administered a long-acting GnRH agonist (Zoladex) by trained medical professionals to suppress endogenous gonadal steroids. Following GnRH agonist administration, men will be administered 1.25g/day (SUPPRESS) of topical 1% testosterone gel (AndroGel, Abbvie, North Chicago, IL) to be applied to the shoulders, upper arms, and/or stomach area daily.

Drug: Goserelin 3.6 MG; Other: Multi-Stressor Training; Drug: Testosterone gel (AndroGel 1.25g)

Hormonal Contraceptive Use (women): Multi-stressor training + Hormonal Contraceptive Use

ACTIVE COMPARATOR

Female participants who report that they are currently using hormonal contraception will undergo the multi-stressor training program.

Other: Multi-Stressor Training

REPLACE (men): Multi-Stressor Training + Zoladex + AndroGel 5g

EXPERIMENTAL

Following GnRH agonist administration, men will be administered 5g/day (REPLACE) of topical 1% testosterone gel (AndroGel, Abbvie, North Chicago, IL) to be applied to the shoulders, upper arms, and/or stomach area daily.

Drug: Goserelin 3.6 MG; Other: Multi-Stressor Training; Drug: Testosterone gel (AndroGel 5g)

Interventions

Goserelin 3.6 MG DRUG

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.

Also known as: Zoladex

REPLACE (men): Multi-Stressor Training + Zoladex + AndroGel 5g; SUPPRESS (men): Multi-Stressor Training + Zoladex + AndroGel 1.25g

Multi-Stressor Training OTHER

A 4-week physical training program that mimics military training.

Hormonal Contraceptive Use (women): Multi-stressor training + Hormonal Contraceptive Use; REPLACE (men): Multi-Stressor Training + Zoladex + AndroGel 5g; STRESS (men + women): Multi-Stressor Training; SUPPRESS (men): Multi-Stressor Training + Zoladex + AndroGel 1.25g

Testosterone gel (AndroGel 5g) DRUG

Male subjects will be randomly assigned to receive a topical testosterone gel (5g dose).

REPLACE (men): Multi-Stressor Training + Zoladex + AndroGel 5g

Testosterone gel (AndroGel 1.25g) DRUG

Male subjects will be randomly assigned to receive a topical testosterone gel (1.25g dose).

SUPPRESS (men): Multi-Stressor Training + Zoladex + AndroGel 1.25g

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-40 years
• body mass index (BMI) 18-30 kg/m2
• weight stable (±10 lbs) in past 2 months
• takes part in moderate physical activity for at least 150 minutes/week
• currently free of upper or lower body /extremity injury or impairment
• able to commit to study duration
• agrees to adhere to study requirements
• not taking prescription medications or be willing to refrain from medication prior to and throughout the study period, unless approved by study physician
• in women, eumenorrheic (cycles of 26-35 days) OR using monophasic oral contraceptive pills with norethindrone acetate (e.g., first generation progestin) for previous 3 months
• \) Current smoker 2) current clinical diagnosis of an eating disorder 3) use of medication incompatible with measurement of reproductive and metabolic hormones or which may interfere with any of the study outcomes; with the exception of approved contraceptives for the contraceptive STRESS \& CONTROL groups 4) current oligo/amenorrhea in women 5) any metabolic or endocrine disease 6) has been diagnosed with a medical condition, physical or psychological, that currently prevents potential subjects from exercising 7) currently pregnant or becomes pregnant during the study 8) history of heart condition OR high blood pressure 9) treating physician requires subject participates in medically supervised physical activity only 10) history of drug addiction, or regular use of recreational drugs 11) currently undergoing treatment for or have a history of mental health conditions 12) Current diagnoses of disorders known to affect bone metabolism including hyperthyroidism, hyperparathyroidism, osteomalacia, Cushing's, diabetes mellitus or renal insufficiency 13) Current use of medications known to affect bone metabolism including estrogens, androgens, anti-estrogens, bisphosphonates (oral bisphosphonates within one year of the baseline visit or IV bisphosphonates within three years of the baseline visit), calcitonin, fluoride, oral or inhaled glucocorticoids, suppressive doses of thyroxine, lithium, pharmacological doses of vitamin D (greater than 2000 IU/day), anti-convulsants, depot medroxyprogesterone within 6 months; with the exception of approved contraceptives for the contraceptive STRESS \& CONTROL groups 14) History of deep vein thrombosis, pulmonary embolism, or clotting disorders. 15) History of stroke or myocardial infarction 16) Fracture within the last 6 months. 17) Systolic blood pressure \> 160 or diastolic blood pressure \> 95 18) Active substance abuse 19) History of hereditary angioedema 20) History of chest pain at rest, during daily activities of living, or when performing physical activity 21) Musculoskeletal injury removing subject from physical activity for more than a month within the past 2 years 22) Recreational drug use more than 2 times per month in each of the previous 6 months 23) Self-reported vision is worse than 20/20. 24) Personal history or history of a first-degree relative with breast cancer 25) Participated and taken investigational drug in any other clinical trial (including bioequivalence study) within six months prior to study drug administration 26) Diagnosed with eating disorder 27) Have food allergies, intolerance, restriction, or special diet needs 28) History of endometriosis 29) Current diagnosis of reproductive health issues, such as ovarian cysts, PCOS, pelvic lesions, undiagnosed ovarian enlargement 30) Have undiagnosed abnormal vaginal bleeding 31) Currently breastfeeding or within 2 months after stopping breastfeeding 32) Frequent headaches accompanied by vision changes (indicative of possible pituitary pathology)
• For SUPPRESS and REPLACE:
• listed above 33) PSA \>3 ng/mL) 34) Serum 25-hydroxyvitamin D \< 20 ng/mL 35) Thyroid dysfunction 36) Serum creatinine \> 2 mg/dL 37) Personal history or history of a first-degree relative with breast cancer 38) Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \> 2x the upper limit of normal 39) Serum bilirubin \> 2 mg/dL 40) Serum alkaline phosphatase \> 150 U/L 41) Plasma hemoglobin \< 10 gm/dL 42) Hematocrit \> 50 43) In men, Serum testosterone level \< 270 or \> 1070 ng/dL (\< 9 or \> 37 nmol/ L) 44) Triglycerides \> 150 fasting

Sponsors & Collaborators

• Bradley Nindl: lead
• U.S. Army Medical Research and Development Command: collaborator

Study Sites (1)

Neuromuscular Research Laboratory

Pittsburgh, Pennsylvania, 15203, United States

RECRUITING

Related Links

• Lab Website

MeSH Terms

Conditions

Hypogonadism

Interventions

Goserelin; Testosterone

Condition Hierarchy (Ancestors)

Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones

Study Officials

• Bradley C Nindl, PhD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bradley C Nindl, PhD

CONTACT

412-246-0460; bnindl@pitt.edu

Kristin J Koltun, PhD

CONTACT

412-246-0460; kjk116@pitt.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 6, 2024
• First Posted: June 13, 2024
• Study Start: July 15, 2024
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: August 18, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP
• Time Frame: Beginning 1 year and ending 5 years following publication.
• Access Criteria: Investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose. For individual participant data meta-analysis. Proposals should be directed to bnindl@pitt.edu. To gain access, data requesters will need to sign a data access agreement.

Locations

US (1)