Does Human Skeletal Muscle Possess an Epigenetic Memory of Testosterone?
- Conditions
- Age-Related SarcopeniaHealthy AgingTestosterone Deficiency
- Interventions
- Drug: SalineDrug: Saline + Resistance exercise training
- Registration Number
- NCT05964920
- Lead Sponsor
- Norwegian School of Sport Sciences
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Male
- Target Recruitment
- 40
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Resistance exercise training + Testosterone Undecanoate Testosterone Undecanoate + Resistance exercise training The resistance exercise training + testosterone group will complete 10-week treatment period where they undergo a period of structured, progressive resistance training and receive two testosterone undecanoate (Nebido) injections (1000 mg/4 ml at baseline and 500 mg/2 ml week 3). They will then undergo a 12-week period with no treatment and no training, where they return to their regular habitual daily physical activity. Before they undertake a second period of structured, progressive resistance training for 10-weeks. Questionnaires, physiological and psychological measures, skeletal muscle biopsies and blood samples will be taken at time points of: 1. Baseline (week 0) 2. Treatment period (week 10) 3. Detraining and testosterone abstinence (week 22) 4. Retraining (week 32) Placebo Saline The placebo group will complete 10-week treatment period where they continue with their regular habitual daily physical activity and receive two placebo (saline) injections (at baseline and week 3). They will then undergo a 12-week period with no treatment and no training, where they just do their regular habitual daily physical activity. Before they undertake a period of structured, progressive resistance training for 10-weeks. Questionnaires, physiological and psychological measures, skeletal muscle biopsies and blood samples will be taken at time points of: 1. Baseline (week 0) 2. Treatment period (week 10) 3. Detraining and placebo abstinence (week 22) 4. Retraining (week 32) Resistance exercise training + Placebo Saline + Resistance exercise training The resistance exercise training + placebo group will complete 10-week treatment period where they undergo a period of structured, progressive resistance training and receive two placebo (saline) injections (at baseline and week 3). They will then undergo a 12-week period with no treatment and no training, where they return to their regular habitual daily physical activity. Before they undertake a second period of structured, progressive resistance training for 10-weeks. Questionnaires, physiological and psychological measures, skeletal muscle biopsies and blood samples will be taken at time points of: 1. Baseline (week 0) 2. Treatment period (week 10) 3. Detraining and placebo abstinence (week 22) 4. Retraining (week 32) Testosterone Undecanoate Testosterone Undecanoate The testosterone group will complete 10-week treatment period where they continue with their regular habitual daily physical activity and receive two testosterone undecanoate (Nebido) injections (1000 mg/4 ml at baseline and 500 mg/2 ml week 3). They will then undergo a 12-week period with no treatment and no training, where they just do their regular habitual daily physical activity. Before they undertake a period of structured, progressive resistance training for 10-weeks. Questionnaires, physiological and psychological measures, skeletal muscle biopsies and blood samples will be taken at time points of: 1. Baseline (week 0) 2. Treatment period (week 10) 3. Detraining and testosterone abstinence (week 22) 4. Retraining (week 32)
- Primary Outcome Measures
Name Time Method Skeletal muscle size and cross-sectional area (CSA) Baseline and week 5,10, 16, 22, 27, 32 Change and differences in skeletal muscle size and CSA measured by ultrasound
Skeletal muscle fibre CSA Baseline and weeks 10, 22, 32 Change and differences in skeletal muscle fibre CSA measure determined by immunohistochemistry
Fat-free mass Baseline and weeks 10, 22, 32 Change and differences in fat-free mass (g) measured by dual x-ray absorptiometry (DEXA).
- Secondary Outcome Measures
Name Time Method Gene expression in skeletal muscle and blood Baseline and weeks 10, 22, 32 Gene expression measured in difference/fold change values relative to appropriate controls.
DNA methylation in skeletal muscle and blood Baseline and weeks 10, 22, 32 Methylation measured in difference/fold change values relative to appropriate controls.
Dynamic muscle strength Baseline and weeks 5, 10, 16, 22, 27, 32 Change and differences in 1-repetition maximum
Muscle force-velocity profiling 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
Myonuclei Baseline and weeks 10, 22, 32 Change and differences in number of myonuclei determined by immunohistochemistry
Satellite cells Baseline and weeks 10, 22, 32 Change and differences in number of satellite cells determined by immunohistochemistry
Isometric muscle strength Baseline and weeks 5, 10, 16, 22, 27, 32 Change and differences in peak muscle strength (N) using isokinetic dynamometry
Trial Locations
- Locations (1)
Norwegian School of Sport Sciences
🇳🇴Oslo, Norway