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Healthy AgingPhase 2/3NCT05964920

Does Human Skeletal Muscle Possess an Epigenetic Memory of Testosterone?

A Phase 2/3 study testing Saline, Testosterone Undecanoate and Saline + Resistance exercise training in people with Healthy Aging and Age-Related Sarcopenia, run by Norwegian School of Sport Sciences at 1 site in Norway.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 55 to 70 years, men onlyHealthy volunteers can take part
What is being tested?
Saline, Testosterone Undecanoate and Saline + Resistance exercise training
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
45 participants
Where
1 siteNorway
Study dates
1 Sep 2024to 6 Feb 2026
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 55 to 70 years
  • Men only
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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%
Show all 20Show fewer
  • 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 locations and contacts

1 site in 1 country.

Norway1 site

  • Norwegian School of Sport Sciences

    Oslo, Oslo, 0863

Other trials in Norway

About this study

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.

Being tested
Saline, Testosterone Undecanoate, Saline + Resistance exercise training, Testosterone Undecanoate + Resistance exercise training
Keywords
Healthy aging, Preventing Age-related Sarcopenia, Overcoming Anabolic Resistance, Anti-Doping

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SalineDrug

    Also called Placebo

    Two placebo injections one at baseline and one week 3.

  • Testosterone UndecanoateDrug

    Also called Nebido, Grünenthal (Grünenthal Norway AS)

    Two testosterone undecanoate injections, 1000 mg/4 ml at baseline, 500 mg/2 ml at week 3.

  • Saline + Resistance exercise trainingDrug

    Also called Placebo + Resistance exercise training

    Two placebo injections one at baseline and one week 3 and10 weeks of supervised, structured, progressive resistance training.

  • Testosterone Undecanoate + Resistance exercise trainingDrug

    Also called Nebido, Grünenthal (Grünenthal Norway AS) + 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.

Study groups in NCT05964920
Study groupRoleWhat they receive
PlaceboPlacebo comparatorThe 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)
Receives: Drug: Saline
Testosterone UndecanoateExperimentalThe 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)
Receives: Drug: Testosterone Undecanoate
Resistance exercise training + PlaceboPlacebo comparatorThe 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)
Receives: Drug: Saline + Resistance exercise training
Resistance exercise training + Testosterone UndecanoateExperimentalThe 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)
Receives: Drug: Testosterone Undecanoate + Resistance exercise training

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Fat-free mass

    Change and differences in fat-free mass (g) measured by dual x-ray absorptiometry (DEXA).

    Measured: Baseline and weeks 10, 22, 32

  2. Skeletal muscle size and cross-sectional area (CSA)

    Change and differences in skeletal muscle size and CSA measured by ultrasound

    Measured: Baseline and week 5,10, 16, 22, 27, 32

  3. Skeletal muscle fibre CSA

    Change and differences in skeletal muscle fibre CSA measure determined by immunohistochemistry

    Measured: Baseline and weeks 10, 22, 32

Secondary outcomes (7)

  1. DNA methylation in skeletal muscle and blood

    Methylation measured in difference/fold change values relative to appropriate controls.

    Measured: Baseline and weeks 10, 22, 32

  2. Gene expression in skeletal muscle and blood

    Gene expression measured in difference/fold change values relative to appropriate controls.

    Measured: Baseline and weeks 10, 22, 32

  3. Myonuclei

    Change and differences in number of myonuclei determined by immunohistochemistry

    Measured: Baseline and weeks 10, 22, 32

  4. Satellite cells

    Change and differences in number of satellite cells determined by immunohistochemistry

    Measured: Baseline and weeks 10, 22, 32

  5. Isometric muscle strength

    Change and differences in peak muscle strength (N) using isokinetic dynamometry

    Measured: Baseline and weeks 5, 10, 16, 22, 27, 32

  6. Dynamic muscle strength

    Change and differences in 1-repetition maximum

    Measured: Baseline and weeks 5, 10, 16, 22, 27, 32

  7. Muscle force-velocity profiling

    Change and differences in force (N) and velocity (m/s) derived from a 10-repetition FV-test

    Measured: Baseline and weeks 5, 10, 16, 22, 27, 32

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jul 2023
  2. Study start1 Sep 2024
  3. Primary completion22 Dec 2025
  4. Study completion6 Feb 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
45 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05964920
Sponsor's protocol ID
TESTO-MEM
Status last verified
Mar 2026
First submitted
16 Jun 2023
Last updated
6 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: 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.

Publications

  • 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.

    PubMed 24167222

  • 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.

    PubMed 29382913

  • 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.

    PubMed 30862794

  • 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.

    PubMed 37154489

  • 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.

    PubMed 31568675

  • 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.

    PubMed 26349924

  • 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.

    PubMed 34870208

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Saline, Testosterone Undecanoate and Saline + Resistance exercise training in people with Healthy Aging and Age-Related Sarcopenia, run by Norwegian School of Sport Sciences at 1 site in Norway.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Fat-free mass (time frame: Baseline and weeks 10, 22, 32). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05964920, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2026; AzTrials last refreshed its copy on 6 Nov 2026.

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