Healthy Aging Clinical Trial
Official title:
Does Human Skeletal Muscle Possess an Epigenetic Memory of Testosterone?
Verified date | November 2023 |
Source | Norwegian School of Sport Sciences |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Not yet recruiting |
Enrollment | 40 |
Est. completion date | July 30, 2025 |
Est. primary completion date | July 30, 2025 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | Male |
Age group | 55 Years to 70 Years |
Eligibility | 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 |
Country | Name | City | State |
---|---|---|---|
n/a |
Lead Sponsor | Collaborator |
---|---|
Norwegian School of Sport Sciences | Oslo University Hospital |
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Skeletal muscle stiffness | Change and differences in skeletal muscle stiffness measured by shear wave ultrasonography | Baseline and weeks 10, 22, 32 | |
Other | Skeletal muscle tissue characteristics | Change and differences in skeletal muscle tissue characteristics determined by immunohistochemistry of muscle biopsies | Baseline and weeks 10, 22, 32 | |
Other | Bone mineral density | Change and differences in bone mineral density (g/cm2) measured by DEXA | Baseline and weeks 10, 22, 32 | |
Other | Bone health | Change and differences in bone health determined by bone health biomarkers in blood | Baseline and weeks 10, 22, 32 | |
Other | 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 | |
Other | 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 | |
Other | 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 | |
Other | 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 | |
Other | 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 | |
Other | 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 | |
Other | 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 | |
Other | 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 | |
Other | 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 | |
Other | Mania | Change and differences in Altman Self-Rating Mania Scale (ASRM) score | Baseline and weeks 5, 10, 16, 22, 27, 32 | |
Other | Suicide thoughts | Change and differences in Suicide thoughts from Montgomery and Åsberg Depression Rating Scale | Baseline and weeks 5, 10, 16, 22, 27, 32 | |
Other | Cognitive function | Change and differences in cognitive function measured by rapid visual information processing | Baseline and weeks 5, 10, 16, 22, 27, 32 | |
Other | Raadiness to train | Change and differences in readiness to train questionnaire score | Baseline and weekly up to week 10, and weekly from week 22 up to week 32 | |
Other | 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 | |
Other | 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 | |
Other | 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 | |
Other | 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 | |
Primary | Fat-free mass | Change and differences in fat-free mass (g) measured by dual x-ray absorptiometry (DEXA). | Baseline and weeks 10, 22, 32 | |
Primary | 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 | |
Primary | Skeletal muscle fibre CSA | Change and differences in skeletal muscle fibre CSA measure determined by immunohistochemistry | Baseline and weeks 10, 22, 32 | |
Secondary | DNA methylation in skeletal muscle and blood | Methylation measured in difference/fold change values relative to appropriate controls. | Baseline and weeks 10, 22, 32 | |
Secondary | Gene expression in skeletal muscle and blood | Gene expression measured in difference/fold change values relative to appropriate controls. | Baseline and weeks 10, 22, 32 | |
Secondary | Myonuclei | Change and differences in number of myonuclei determined by immunohistochemistry | Baseline and weeks 10, 22, 32 | |
Secondary | Satellite cells | Change and differences in number of satellite cells determined by immunohistochemistry | Baseline and weeks 10, 22, 32 | |
Secondary | Isometric muscle strength | Change and differences in peak muscle strength (N) using isokinetic dynamometry | Baseline and weeks 5, 10, 16, 22, 27, 32 | |
Secondary | Dynamic muscle strength | Change and differences in 1-repetition maximum | Baseline and weeks 5, 10, 16, 22, 27, 32 | |
Secondary | 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 |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05596474 -
Effect of Beet-root Juice and PBM Treatments on Muscle Fatigue
|
N/A | |
Active, not recruiting |
NCT05203848 -
Community Dance Program (CDP) for Older Adults
|
Phase 1 | |
Not yet recruiting |
NCT06455982 -
Reduced Carbohydrates + Ketogenic Supplement on Energy Metabolism
|
N/A | |
Completed |
NCT04084457 -
Investigating the Effects of Daily Consumption of Blueberry (Poly)Phenols on Vascular Function and Cognitive Performance
|
N/A | |
Recruiting |
NCT05006261 -
A Mobile Tai Chi Platform for Fall Prevention in Older Adults - Phase II
|
N/A | |
Active, not recruiting |
NCT04262674 -
Non-invasive, Wearable Multi-parameter System for the Early Prediction of Cognitive Decline and Dementia in Older Adults
|
N/A | |
Completed |
NCT02218411 -
Video-supported Group-based Otago Exercise Programme on Physical Performance in Older Adults.
|
Phase 1 | |
Active, not recruiting |
NCT05961319 -
Smart Home Technologies for Assessing and Monitoring Frailty in Older Adults
|
||
Completed |
NCT05213091 -
The Effect of Otago Exercises in the Elderly
|
N/A | |
Active, not recruiting |
NCT04904068 -
Functional Neuroimaging in Parkinson's Disease
|
||
Completed |
NCT04348162 -
Food Anthocyanins and Flavanols as a Strategy for a Healthy Ageing: Cardiovascular Health and Cognitive Performance
|
N/A | |
Completed |
NCT05941143 -
Effect of Mindfulness on EEG Brain Activity for Cognitive and Psychological Well-being in the Elderly
|
N/A | |
Completed |
NCT06022094 -
Effect of a Two-month Carbohydrate-restricted Diet on Energy Metabolism in a Seniors' Residence
|
N/A | |
Active, not recruiting |
NCT06162871 -
Social Participation and Healthy Aging
|
N/A | |
Completed |
NCT05207501 -
Effects of Different Moderate-intensity Exercise Methods on Health in the Elderly
|
N/A | |
Recruiting |
NCT04986787 -
Novel, Individualized Brain Stimulation, Network-based Approaches to Improve Cognition
|
N/A | |
Completed |
NCT05933798 -
China Pilot of ICOPE (Integrated Care for Older People) in Chaoyang
|
N/A | |
Recruiting |
NCT05394363 -
Generation Victoria Cohort 2020s: A Statewide Longitudinal Cohort Study of Victorian Children and Their Parents
|
||
Completed |
NCT04786665 -
Strawberries, Cognition, and Vascular Health
|
N/A | |
Completed |
NCT05290571 -
Modified Otago Exercise Program on Balance Performance
|
N/A |