Does Human Skeletal Muscle Possess an Epigenetic Memory of Testosterone?

Norwegian School of Sport Sciences

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Age-Related Sarcopenia; Testosterone Deficiency; Healthy Aging

Treatments: Drug: Testosterone Undecanoate; Drug: Testosterone Undecanoate + Resistance exercise training; Drug: Saline + Resistance exercise training; Drug: Saline

Study type: Interventional

Funder types: Other

Identifiers

NCT05964920

TESTO-MEM

Details and patient eligibility

About

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.

Enrollment: 40 estimated patients

Sex: Male

Ages: 55 to 70 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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40 participants in 4 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

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)

Treatment:

Drug: Saline

Testosterone Undecanoate

Experimental group

Description:

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)

Treatment:

Drug: Testosterone Undecanoate

Resistance exercise training + Placebo

Placebo Comparator group

Description:

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)

Treatment:

Drug: Saline + Resistance exercise training

Resistance exercise training + Testosterone Undecanoate

Experimental group

Description:

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)

Treatment:

Drug: Testosterone Undecanoate + Resistance exercise training