Adaptions and Resiliency to Multi-Stressor OpeRations

Hypogonadism Clinical Trial

— ARMOR  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06455969
• Other study ID #: STUDY23090134
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: June 17, 2024
• Est. completion date: August 1, 2026

Study information

• Verified date: June 2024
• Source: University of Pittsburgh
• Contact: Bradley C Nindl, PhD
• Phone: 412-246-0460
• Email: bnindl[@]pitt.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 120
• Est. completion date: August 1, 2026
• Est. primary completion date: August 1, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

1. Age 18-40 years

2. body mass index (BMI) 18-30 kg/m2

3. weight stable (±10 lbs) in past 2 months

4. takes part in moderate physical activity for at least 150 minutes/week

5. currently free of upper or lower body /extremity injury or impairment

6. able to commit to study duration

7. agrees to adhere to study requirements

8. not taking prescription medications or be willing to refrain from medication prior to and throughout the study period, unless approved by study physician

9. in men, total testosterone concentration within normal physiological range (300-1000 ng/dL)

10. in women, eumenorrheic (cycles of 26-35 days) and not using hormonal contraceptives for previous 3 months

Exclusion Criteria:

1. 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

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. irregular lab results (e.g., PSA >3 ng/mL)

13. Current diagnoses of disorders known to affect bone metabolism including hyperthyroidism, hyperparathyroidism, osteomalacia, Cushing's, diabetes mellitus or renal insufficiency

14. 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.

15. History of deep vein thrombosis, pulmonary embolism, or clotting disorders.

16. History of stroke or myocardial infarction

17. Serum 25-hydroxyvitamin D < 20 ng/mL

18. Thyroid dysfunction

19. Serum creatinine > 2 mg/dL

20. Personal history or history of a first-degree relative with breast cancer

21. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 2x the upper limit of normal

22. Serum bilirubin > 2 mg/dL

23. Serum alkaline phosphatase > 150 U/L

24. Plasma hemoglobin < 10 gm/dL

25. Hematocrit > 50

26. Fracture within the last 6 months.

27. Serum testosterone level < 270 or > 1070 ng/dL

28. Systolic blood pressure > 160 or diastolic blood pressure > 95

29. Active substance abuse

30. Triglycerides > 150 fasting

31. History of hereditary angioedema

32. History of chest pain at rest, during daily activities of living, or when performing physical activity

33. Musculoskeletal injury removing subject from physical activity for more than a month within the past 2 years

34. Recreational drug use more than 2 times per month in each of the previous 6 months

35. Self-reported vision is worse than 20/20.

36. Personal history or history of a first-degree relative with breast cancer

37. Experienced a fracture within the last 6 months

38. participated and taken investigational drug in any other clinical trial (including bioequivalence study) within six months prior to study drug administration

39. Diagnosed with eating disorder

40. Have food allergies, intolerance, restriction, or special diet needs

41. History of endometriosis

42. Current diagnosis of reproductive health issues, such as ovarian cysts, PCOS, pelvic lesions, undiagnosed ovarian enlargement

43. Have undiagnosed abnormal vaginal bleeding

44. Currently breastfeeding or within 2 months after stopping breastfeeding

45. Have dietary restrictions

Related Conditions & MeSH terms

• Hypogonadism
• Musculoskeletal Injury

Intervention

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).
• Testosterone gel (AndroGel 1.25g)
Male subjects will be randomly assigned to receive a topical testosterone gel (1.25g dose).
• Estradiol / Levonorgestrel Transdermal System [Climara Pro]
Female subjects will be randomly assigned to receive a estrogen/ progesterone patch.
• Placebo Patch
Female subjects will be randomly assigned to receive a placebo patch identical to the Climara Pro patch.

Locations

Country	Name	City	State
United States	Neuromuscular Research Laboratory	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Bradley Nindl	U.S. Army Medical Research and Development Command

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Biomechanical: Tendon Cross-Sectional Area, change from baseline and throughout training, mean		Through study completion, an average of 8 weeks
Primary	Biomechanical: Tendon Shear Wave Elastography, change from baseline and throughout training, mean		Through study completion, an average of 8 weeks
Primary	Biomechanical: Tendon Thickness, change from baseline and throughout training, mean		Through study completion, an average of 8 weeks
Primary	Biomechanical: Quadriceps Muscle Cross-sectional Area, change from baseline and throughout training, mean		Through study completion, an average of 8 weeks
Primary	Biomechanical: Quadricpes Muscle Echointensity, change from baseline and throughout training, mean		Through study completion, an average of 8 weeks
Primary	Body composition: Lean mass, change from baseline, mean		Through study completion, an average of 8 weeks
Primary	Body Composition: Fat mass, change from baseline, mean		Through study completion, an average of 8 weeks
Primary	Body Composition: Body mass, change from baseline and throughout training, mean		Through study completion, an average of 8 weeks
Primary	Body Composition: Body Fat Percentage, change from baseline, mean		Through study completion, an average of 8 weeks
Primary	Biochemical: Bone turnover markers (CTx + P1NP), change from baseline, mean		Through study completion, an average of 8 weeks
Primary	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	Bone microarchitecture: High Resolution- peripheral Computed Tomography, change from baseline, mean		Through study completion, an average of 8 weeks
Secondary	Biochemical: Cell culture, extracellular vesicles, micro- RNAs, change from baseline and throughout study, mean		Through study completion, an average of 8 weeks
Secondary	Biochemical: Measures of inflammation (IL6, IL-1B, TNFa, CRP), change from baseline and throughout study, mean		Through study completion, an average of 8 weeks
Secondary	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

External Links

•   Lab Website