Does Human Skeletal Muscle Possess an Epigenetic Memory of Testosterone?
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Skeletal muscle size and cross-sectional area (CSA)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 55 Years 至 70 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Placebo
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:
- Baseline (week 0)
- Treatment period (week 10)
- Detraining and placebo abstinence (week 22)
- Retraining (week 32)
干预措施: Saline (Drug)
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:
- Baseline (week 0)
- Treatment period (week 10)
- Detraining and testosterone abstinence (week 22)
- Retraining (week 32)
干预措施: Testosterone Undecanoate (Drug)
Resistance exercise training + Placebo
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:
- Baseline (week 0)
- Treatment period (week 10)
- Detraining and placebo abstinence (week 22)
- Retraining (week 32)
干预措施: Saline + Resistance exercise training (Drug)
Resistance exercise training + Testosterone Undecanoate
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:
- Baseline (week 0)
- Treatment period (week 10)
- Detraining and testosterone abstinence (week 22)
- Retraining (week 32)
干预措施: Testosterone Undecanoate + Resistance exercise training (Drug)
结局指标
主要结局
Skeletal muscle size and cross-sectional area (CSA)
时间窗: 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
时间窗: Baseline and weeks 10, 22, 32
Change and differences in skeletal muscle fibre CSA measure determined by immunohistochemistry
Fat-free mass
时间窗: Baseline and weeks 10, 22, 32
Change and differences in fat-free mass (g) measured by dual x-ray absorptiometry (DEXA).
次要结局
- Gene expression in skeletal muscle and blood(Baseline and weeks 10, 22, 32)
- DNA methylation in skeletal muscle and blood(Baseline and weeks 10, 22, 32)
- Satellite cells(Baseline and weeks 10, 22, 32)
- Myonuclei(Baseline and weeks 10, 22, 32)
- Dynamic muscle strength(Baseline and weeks 5, 10, 16, 22, 27, 32)
- Muscle force-velocity profiling(Baseline and weeks 5, 10, 16, 22, 27, 32)
- Isometric muscle strength(Baseline and weeks 5, 10, 16, 22, 27, 32)
研究者
Adam Sharples
Professor
Norwegian School of Sport Sciences