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Completed

NCT Number: NCT05964920

Does Human Skeletal Muscle Possess an Epigenetic Memory of Testosterone?

This project's primary aim of this double-blinded, randomised, placebo-controlled trial is to investigate whether short-term testosterone administration +/- resistance exercise training induces a muscle memory response that can lead to longer-lasting benefits in aged human skeletal muscle.

The investigators will provide older men with the anabolic hormone, testosterone or placebo, with or without resistance training, followed by a period of testosterone abstinence and detraining, followed by a subsequent repeated period of resistance training (retraining). This will help determine if earlier encounters with short-term testosterone administration can be "remembered" and if adaptation to later retraining can be enhanced as a consequence of encountering testosterone earlier.

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Key information

Conditions

Healthy Aging Age-Related Sarcopenia Testosterone Deficiency

Age range

55 year–70 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Norwegian School of Sport Sciences

Oslo, 0863, Norway

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Sedentary males
  • 55-70 years old
  • Serum testosterone levels >8 nmol/L measured in the morning
  • Without any known illness, disease or other conditions
  • Undergone screening through medical questionnaire, physical examination, routine blood tests and urine sample
  • Written informed consent received

Exclusion criteria

  • Current or previous participation in a formal exercise regime
  • A BMI < 18 or > 30 kg·m2
  • Hypersensitivity to the study drug or to any of its constituents
  • Active cardiovascular disease: uncontrolled hypertension (BP > 160/100 mmHg), angina, heart failure (class III/IV), arrhythmia, right to left cardiac shunt, recent cardiac event
  • Family history of early (<55y) death from cardiovascular disease
  • Haematocrit >50%
  • Malignancy
  • Prostate-specific antigen (PSA) >4 ng/mL
  • Lower urinary tract symptoms
  • Taking beta-adrenergic blocking agents, statins, non-steroidal anti-inflammatory drugs
  • Cerebrovascular disease: previous stroke, aneurysm (large vessel or intracranial), epilepsy
  • Respiratory diseases including: pulmonary hypertension, chronic obstructive pulmanary disease (COPD), asthma, sleep apnoea
  • Metabolic disease: hyper and hypo parathyroidism, untreated hyper and hypothyroidism, Cushing's disease, type 1 or 2 diabetes
  • Active inflammatory bowel or renal disease
  • Current or previous steroid treatment or hormone replacement therapy
  • Clotting dysfunction
  • Musculoskeletal or neurological disorders
  • Alcohol or drug abuse
  • Receiving oral anticoagulants
  • Serum testosterone levels above the reference range for 50 year olds (>32 nmol/L) (Bjerner et al., 2009) measured in the morning 1

Treatment and study plan

Saline

Drug

Two placebo injections one at baseline and one week 3.

Other names: Placebo

Testosterone Undecanoate

Drug

Two testosterone undecanoate injections, 1000 mg/4 ml at baseline, 500 mg/2 ml at week 3.

Other names: Nebido, Grünenthal (Grünenthal Norway AS)

Saline + Resistance exercise training

Drug

Two placebo injections one at baseline and one week 3 and10 weeks of supervised, structured, progressive resistance training.

Other names: Placebo + Resistance exercise training

Testosterone Undecanoate + Resistance exercise training

Drug

Two testosterone undecanoate injections, 1000 mg/4 ml at baseline, 500 mg/2 ml at week 3 and 10 weeks of supervised, structured, progressive resistance training.

Other names: Nebido, Grünenthal (Grünenthal Norway AS) + Resistance exercise training

Primary outcomes

  1. Fat-free mass

    Time frame: Baseline and weeks 10, 22, 32

    Change and differences in fat-free mass (g) measured by dual x-ray absorptiometry (DEXA).

  2. Skeletal muscle size and cross-sectional area (CSA)

    Time frame: Baseline and week 5,10, 16, 22, 27, 32

    Change and differences in skeletal muscle size and CSA measured by ultrasound

  3. Skeletal muscle fibre CSA

    Time frame: Baseline and weeks 10, 22, 32

    Change and differences in skeletal muscle fibre CSA measure determined by immunohistochemistry

Secondary outcomes

  1. DNA methylation in skeletal muscle and blood

    Time frame: Baseline and weeks 10, 22, 32

    Methylation measured in difference/fold change values relative to appropriate controls.

  2. Gene expression in skeletal muscle and blood

    Time frame: Baseline and weeks 10, 22, 32

    Gene expression measured in difference/fold change values relative to appropriate controls.

  3. Myonuclei

    Time frame: Baseline and weeks 10, 22, 32

    Change and differences in number of myonuclei determined by immunohistochemistry

  4. Satellite cells

    Time frame: Baseline and weeks 10, 22, 32

    Change and differences in number of satellite cells determined by immunohistochemistry

  5. Isometric muscle strength

    Time frame: Baseline and weeks 5, 10, 16, 22, 27, 32

    Change and differences in peak muscle strength (N) using isokinetic dynamometry

  6. Dynamic muscle strength

    Time frame: Baseline and weeks 5, 10, 16, 22, 27, 32

    Change and differences in 1-repetition maximum

  7. Muscle force-velocity profiling

    Time frame: Baseline and weeks 5, 10, 16, 22, 27, 32

    Change and differences in force (N) and velocity (m/s) derived from a 10-repetition FV-test

Other outcomes

  1. Skeletal muscle stiffness

    Time frame: Baseline and weeks 10, 22, 32

    Change and differences in skeletal muscle stiffness measured by shear wave ultrasonography

  2. Skeletal muscle tissue characteristics

    Time frame: Baseline and weeks 10, 22, 32

    Change and differences in skeletal muscle tissue characteristics determined by immunohistochemistry of muscle biopsies

  3. Bone mineral density

    Time frame: Baseline and weeks 10, 22, 32

    Change and differences in bone mineral density (g/cm2) measured by DEXA

  4. Bone health

    Time frame: Baseline and weeks 10, 22, 32

    Change and differences in bone health determined by bone health biomarkers in blood

  5. Blood volume, haemoglobin and lean body mass

    Time frame: Baseline and weeks 10, 22, 32

    To investigate the association between blood volume, haemoglobin mass and lean body mass measured by carbon monoxide (CO) rebreathing and DEXA.

  6. Blood parameters

    Time frame: Baseline and weeks 10, 22, 32

    Change and differences in steroid hormones in blood (testosterone, androstenediol, estradiol, and other relevant steroid markers, reproductive hormones (LH, FSH), binding protein (SHBG), cholesterol (total cholesterol, LDL, HDL), and PSA level, and endocrine biomarkers (IGF-1 and P-III-NP).

  7. Aging males symptoms

    Time frame: Baseline and weeks 5, 10, 16, 22, 27, 32

    Change and differences in Aging male symptoms score (1="none", 5="extremely severe")

  8. Well-being

    Time frame: Baseline and weeks 5, 10, 16, 22, 27, 32

    Change and differences in WHO5 well-being index score (0="at not time", 5="all of the time")

  9. Psychological distress

    Time frame: Baseline and weeks 5, 10, 16, 22, 27, 32

    Change and differences in SCL-10 symptoms score (1="not at all", 4="extremely")

  10. Fatigue

    Time frame: Baseline and weeks 5, 10, 16, 22, 27, 32

    Change and differences in shortened fatigue questionnaire score (1="yes, that is true", 7="no, that is not true")

  11. Sleep

    Time frame: Baseline and weeks 5, 10, 16, 22, 27, 32

    Change and differences in Jenkins sleep scale score (0="not at all", 5="22-31days")

  12. Sexual function

    Time frame: Baseline and weeks 5, 10, 16, 22, 27, 32

    Change and differences in sexual function score (items from Health-related quality of life (HRQOL) questionnaire), (

  13. Body perception

    Time frame: Baseline and weeks 5, 10, 16, 22, 27, 32

    Change and differences in Body Perception Questionnaire very short form score (1=never, 5=always)

  14. Anger

    Time frame: Baseline and weeks 5, 10, 16, 22, 27, 32

    Change and differences in The State Anger subscale of STAXI-2score (0="not at all", 3="very much")

  15. Mania

    Time frame: Baseline and weeks 5, 10, 16, 22, 27, 32

    Change and differences in Altman Self-Rating Mania Scale (ASRM) score

  16. Suicide thoughts

    Time frame: Baseline and weeks 5, 10, 16, 22, 27, 32

    Change and differences in Suicide thoughts from Montgomery and Åsberg Depression Rating Scale

  17. Cognitive function

    Time frame: Baseline and weeks 5, 10, 16, 22, 27, 32

    Change and differences in cognitive function measured by emotion recognition tasks and cognitive reflection tasks

  18. Exercise motivation

    Time frame: Baseline and weekly up to week 10, and weekly from week 22 up to week 32

    Change and differences in perceived motivation score and motivation type

  19. Exercise effort

    Time frame: Baseline and weekly up to week 10, and weekly from week 22 up to week 32

    Change and differences in rating of perceived exertion for effort (Borg CR-10 RPE)

  20. Exercise discomfort

    Time frame: Baseline and weekly up to week 10, and weekly from week 22 up to week 32

    Change and differences in rating of perceived exertion for discomfort (sRPD) score

  21. Session pleasure and displeasure

    Time frame: Baseline and weekly up to week 10, and weekly from week 22 up to week 32

    Change and differences in perceived pleasure/displeasure with the training session using the pleasure/displeasure feeling scale (sPDF), (-5=very bad", 5="very good")

  22. Exercise enjoyment

    Time frame: Baseline and weekly up to week 10, and weekly from week 22 up to week 32

    Change and differences in exercise enjoyment scale score (1="not at all", 7=extraordinary")

  23. Reps in reserve

    Time frame: Baseline and weekly up to week 10, and weekly from week 22 up to week 32

    Change and differences in the ability to predict reps in reserve

Sponsors and collaborators

Lead sponsor

Norwegian School of Sport Sciences

Other

Collaborators

  • Oslo University Hospital

Registry information

Important dates

Study start
2024
Primary completion
2025
Study completion
2026
First posted
Jul 28, 2023
Registry last updated
Mar 6, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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