Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Oslo University Hospital | OTHER |
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | 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:
|
|
| Testosterone Undecanoate | Experimental | 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:
|
|
| Resistance exercise training + Placebo | Placebo Comparator | 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:
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Saline | Drug | Two placebo injections one at baseline and one week 3. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Fat-free mass | Change and differences in fat-free mass (g) measured by dual x-ray absorptiometry (DEXA). | Baseline and weeks 10, 22, 32 |
| Skeletal muscle size and cross-sectional area (CSA) | Change and differences in skeletal muscle size and CSA measured by ultrasound | Baseline and week 5,10, 16, 22, 27, 32 |
| Skeletal muscle fibre CSA | Change and differences in skeletal muscle fibre CSA measure determined by immunohistochemistry | Baseline and weeks 10, 22, 32 |
| Measure | Description | Time Frame |
|---|---|---|
| DNA methylation in skeletal muscle and blood | Methylation measured in difference/fold change values relative to appropriate controls. | Baseline and weeks 10, 22, 32 |
| Gene expression in skeletal muscle and blood |
| Measure | Description | Time Frame |
|---|---|---|
| Skeletal muscle stiffness | Change and differences in skeletal muscle stiffness measured by shear wave ultrasonography | Baseline and weeks 10, 22, 32 |
| Skeletal muscle tissue characteristics | Change and differences in skeletal muscle tissue characteristics determined by immunohistochemistry of muscle biopsies |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Norwegian School of Sport Sciences | Oslo | Oslo | 0863 | Norway |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24167222 | Background | Egner IM, Bruusgaard JC, Eftestol E, Gundersen K. A cellular memory mechanism aids overload hypertrophy in muscle long after an episodic exposure to anabolic steroids. J Physiol. 2013 Dec 15;591(24):6221-30. doi: 10.1113/jphysiol.2013.264457. Epub 2013 Oct 28. | |
| 29382913 | Background | Seaborne RA, Strauss J, Cocks M, Shepherd S, O'Brien TD, van Someren KA, Bell PG, Murgatroyd C, Morton JP, Stewart CE, Sharples AP. Human Skeletal Muscle Possesses an Epigenetic Memory of Hypertrophy. Sci Rep. 2018 Jan 30;8(1):1898. doi: 10.1038/s41598-018-20287-3. |
Not provided
Not provided
No identifiable information will be included in any publication. Genome-Wide DNA Methylation and Gene Expression will be deposited with full open access on Gene Expression Omnibus (GEO) (https://www.ncbi.nlm.nih.gov/geo/) an internationally recognised database. GEO data derived from human samples will be anonymous, with no identifiable information. GEO data will be deposited at the same time as a publication. All non-identifiable results from the project will be ultimately published in peer-reviewed journals. In addition, all image files, raw excel/ .csv / txt /word files for any of the other analyses described above in the methods will be available as either supplementary files on the publisher's website or fully accessible on request to the corresponding author/authors.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Resistance exercise training + Testosterone Undecanoate | Experimental | 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:
|
|
| Testosterone Undecanoate | Drug | Two testosterone undecanoate injections, 1000 mg/4 ml at baseline, 500 mg/2 ml at week 3. |
|
|
| Saline + Resistance exercise training | Drug | Two placebo injections one at baseline and one week 3 and10 weeks of supervised, structured, progressive resistance 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. |
|
|
Gene expression measured in difference/fold change values relative to appropriate controls.
| Baseline and weeks 10, 22, 32 |
| Myonuclei | Change and differences in number of myonuclei determined by immunohistochemistry | Baseline and weeks 10, 22, 32 |
| Satellite cells | Change and differences in number of satellite cells determined by immunohistochemistry | Baseline and weeks 10, 22, 32 |
| Isometric muscle strength | Change and differences in peak muscle strength (N) using isokinetic dynamometry | Baseline and weeks 5, 10, 16, 22, 27, 32 |
| Dynamic muscle strength | Change and differences in 1-repetition maximum | Baseline and weeks 5, 10, 16, 22, 27, 32 |
| Muscle force-velocity profiling | Change and differences in force (N) and velocity (m/s) derived from a 10-repetition FV-test | Baseline and weeks 5, 10, 16, 22, 27, 32 |
| Baseline and weeks 10, 22, 32 |
| Bone mineral density | Change and differences in bone mineral density (g/cm2) measured by DEXA | Baseline and weeks 10, 22, 32 |
| Bone health | Change and differences in bone health determined by bone health biomarkers in blood | Baseline and weeks 10, 22, 32 |
| Blood volume, haemoglobin and lean body mass | To investigate the association between blood volume, haemoglobin mass and lean body mass measured by carbon monoxide (CO) rebreathing and DEXA. | Baseline and weeks 10, 22, 32 |
| Blood parameters | 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). | Baseline and weeks 10, 22, 32 |
| Aging males symptoms | Change and differences in Aging male symptoms score (1="none", 5="extremely severe") | Baseline and weeks 5, 10, 16, 22, 27, 32 |
| Well-being | Change and differences in WHO5 well-being index score (0="at not time", 5="all of the time") | Baseline and weeks 5, 10, 16, 22, 27, 32 |
| Psychological distress | Change and differences in SCL-10 symptoms score (1="not at all", 4="extremely") | Baseline and weeks 5, 10, 16, 22, 27, 32 |
| Fatigue | Change and differences in shortened fatigue questionnaire score (1="yes, that is true", 7="no, that is not true") | Baseline and weeks 5, 10, 16, 22, 27, 32 |
| Sleep | Change and differences in Jenkins sleep scale score (0="not at all", 5="22-31days") | Baseline and weeks 5, 10, 16, 22, 27, 32 |
| Sexual function | Change and differences in sexual function score (items from Health-related quality of life (HRQOL) questionnaire), ( | Baseline and weeks 5, 10, 16, 22, 27, 32 |
| Body perception | Change and differences in Body Perception Questionnaire very short form score (1=never, 5=always) | Baseline and weeks 5, 10, 16, 22, 27, 32 |
| Anger | Change and differences in The State Anger subscale of STAXI-2score (0="not at all", 3="very much") | Baseline and weeks 5, 10, 16, 22, 27, 32 |
| Mania | Change and differences in Altman Self-Rating Mania Scale (ASRM) score | Baseline and weeks 5, 10, 16, 22, 27, 32 |
| Suicide thoughts | Change and differences in Suicide thoughts from Montgomery and Åsberg Depression Rating Scale | Baseline and weeks 5, 10, 16, 22, 27, 32 |
| Cognitive function | Change and differences in cognitive function measured by emotion recognition tasks and cognitive reflection tasks | Baseline and weeks 5, 10, 16, 22, 27, 32 |
| Exercise motivation | Change and differences in perceived motivation score and motivation type | Baseline and weekly up to week 10, and weekly from week 22 up to week 32 |
| Exercise effort | Change and differences in rating of perceived exertion for effort (Borg CR-10 RPE) | Baseline and weekly up to week 10, and weekly from week 22 up to week 32 |
| Exercise discomfort | Change and differences in rating of perceived exertion for discomfort (sRPD) score | Baseline and weekly up to week 10, and weekly from week 22 up to week 32 |
| Session pleasure and displeasure | Change and differences in perceived pleasure/displeasure with the training session using the pleasure/displeasure feeling scale (sPDF), (-5=very bad", 5="very good") | Baseline and weekly up to week 10, and weekly from week 22 up to week 32 |
| Exercise enjoyment | Change and differences in exercise enjoyment scale score (1="not at all", 7=extraordinary") | Baseline and weekly up to week 10, and weekly from week 22 up to week 32 |
| Reps in reserve | Change and differences in the ability to predict reps in reserve | Baseline and weekly up to week 10, and weekly from week 22 up to week 32 |
| 30862794 | Background | Turner DC, Seaborne RA, Sharples AP. Comparative Transcriptome and Methylome Analysis in Human Skeletal Muscle Anabolism, Hypertrophy and Epigenetic Memory. Sci Rep. 2019 Mar 12;9(1):4251. doi: 10.1038/s41598-019-40787-0. |
| 37154489 | Background | Sharples AP, Turner DC. Skeletal muscle memory. Am J Physiol Cell Physiol. 2023 Jun 1;324(6):C1274-C1294. doi: 10.1152/ajpcell.00099.2023. Epub 2023 May 8. |
| 31568675 | Background | Gharahdaghi N, Rudrappa S, Brook MS, Idris I, Crossland H, Hamrock C, Abdul Aziz MH, Kadi F, Tarum J, Greenhaff PL, Constantin-Teodosiu D, Cegielski J, Phillips BE, Wilkinson DJ, Szewczyk NJ, Smith K, Atherton PJ. Testosterone therapy induces molecular programming augmenting physiological adaptations to resistance exercise in older men. J Cachexia Sarcopenia Muscle. 2019 Dec;10(6):1276-1294. doi: 10.1002/jcsm.12472. Epub 2019 Sep 30. |
| 26349924 | Background | Sharples AP, Polydorou I, Hughes DC, Owens DJ, Hughes TM, Stewart CE. Skeletal muscle cells possess a 'memory' of acute early life TNF-alpha exposure: role of epigenetic adaptation. Biogerontology. 2016 Jun;17(3):603-17. doi: 10.1007/s10522-015-9604-x. Epub 2015 Sep 8. |
| 34870208 | Background | Wen Y, Dungan CM, Mobley CB, Valentino T, von Walden F, Murach KA. Nucleus Type-Specific DNA Methylomics Reveals Epigenetic "Memory" of Prior Adaptation in Skeletal Muscle. Function (Oxf). 2021 Aug 5;2(5):zqab038. doi: 10.1093/function/zqab038. eCollection 2021. |
| ID | Term |
|---|---|
| D012965 | Sodium Chloride |
| C010792 | testosterone undecanoate |
| ID | Term |
|---|---|
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |
Not provided
Not provided