Age-Related Sarcopenia, Healthy Aging, Testosterone Deficiency
Conditions
Keywords
Healthy aging, Preventing Age-related Sarcopenia, Overcoming Anabolic Resistance, Anti-Doping
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.
Interventions
DRUGSaline
Two placebo injections one at baseline and one week 3.
DRUGTestosterone Undecanoate
Two testosterone undecanoate injections, 1000 mg/4 ml at baseline, 500 mg/2 ml at week 3.
DRUGSaline + Resistance exercise training
Two placebo injections one at baseline and one week 3 and10 weeks of supervised, structured, progressive resistance training.
DRUGTestosterone Undecanoate + Resistance exercise training
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.
Sponsors
Norwegian School of Sport Sciences
Oslo University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
55 Years to 70 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fat-free mass | Baseline and weeks 10, 22, 32 | Change and differences in fat-free mass (g) measured by dual x-ray absorptiometry (DEXA). |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| DNA methylation in skeletal muscle and blood | Baseline and weeks 10, 22, 32 | Methylation measured in difference/fold change values relative to appropriate controls. |
| 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. |
| 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 |
| 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 |
Countries
Norway
Outcome results
None listed