Does human skeletal muscle possess an epigenetic memory of testosterone

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Norges Idrettshoegskole

Participant type

Healthy volunteers

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Phenomena and Processes [G] - Cell Physiological Phenomena [G04]

Trial duration

1 Aug 2024 → 4 Feb 2026

Decision date (initial)

2023-11-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Norwegian School of Sport Sciences

External identifiers

EU CT number

2023-507815-37-00

ClinicalTrials.gov

NCT05964920

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

To compare the ability to retrain and enhance muscle size after a period of detraining / testosterone abstinence between earlier short-term testosterone groups and placebo controls.

Secondary objectives 2

1. To identify whether human skeletal muscle can “remember” an earlier encounter of short-term testosterone administration by myonuclear accretion and permanence and/or the retention of imprinted epigenetic signatures (DNA methylation).
2. To identify whether receiving short-term testosterone administration will enhance strength and power gains in the retraining period, even after 12 weeks of detraining and testosterone abstinence compared to placebo controls.

Conditions and MedDRA coding

Healthy aging

Study design 3 periods

Regulatory references

Plan to share IPD

Yes

IPD plan description

Genome-wide analysis for both DNA, RNA, and protein samples may be undertaken by commercial services outside the EEA e.g., United Kingdom at The Genome Centre at Queen Mary University of London (QMUL), UK who provides a commercial service for this type of genome-wide analysis. This analysis does not provide any genetic information that can be used to identify anyone or identify defects (e.g., genetic mutation associated with diseases/disorders) or provide any diagnostic or predictive health information about diseases that can be prevented or treated. It only reports on whether the modification of DNA methylation is present or absent and its level of methylation across samples in locations in the genome where methylation occurs e.g., CpG sites. No identifiable information or health information will be provided to these external commercial institutes/companies. The commercial service would simply receive DNA or RNA samples with an associated sample/numerical code, e.g., 01_01, etc.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Sedentary males
2. 55-70 years old
3. Serum testosterone levels >8 nmol/L measured in the morning.
4. Without any known illness, disease or other conditions.
5. Undergone screening through medical questionnaire, physical examination, routine blood tests and urine samples
6. Written informed consent received.

Exclusion criteria 19

1. Current or previous participation in a formal exercise regime.
2. Cerebrovascular disease: previous stroke, aneurysm (large vessel or intracranial), epilepsy.
3. Respiratory diseases including: pulmonary hypertension, COPD, asthma, sleep apnoea.
4. Metabolic disease: hyper and hypo parathyroidism, untreated hyper and hypothyroidism, Cushing's disease, type 1 or 2 diabetes.
5. Active inflammatory bowel or renal disease.
6. Current or previous steroid treatment or hormone replacement therapy.
7. Clotting dysfunction.
8. Musculoskeletal or neurological disorders.
9. Alcohol or drug abuse.
10. A BMI < 18 or > 30 kg·m2.
11. Active cardiovascular disease: uncontrolled hypertension (BP > 160/100 mmHg), angina, heart failure (class III/IV), arrhythmia, right to left cardiac shunt, recent cardiac event
12. Family history of early (<55y) death from cardiovascular disease.
13. Haematocrit >50%
14. Malignancy.
15. Prostate-specific antigen (PSA) >4 ng/mL.
16. Lower urinary tract symptoms
17. Taking beta-adrenergic blocking agents, statins, non-steroidal anti-inflammatory drugs.
18. Receiving oral anticoagulants
19. Serum testosterone levels above the reference range for 50 year olds (>32 nmol/L) (Bjerner et al., 2009) measured in the morning

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Mean differences in fat-free mass, muscle size, and muscle fibre types cross-sectional area (CSA) between placebo or testosterone groups +/- resistance training, measured by DEXA, ultrasound, and muscle biopsies .

Secondary endpoints 2

1. Differences in myonuclear accretion and permanence and/or the retainment of imprinted epigenetic signatures (DNA methylation) and corresponding gene expression in skeletal muscle between placebo or testosterone groups +/- resistance training.
2. Mean differences in strength, velocity and power between placebo and testosterone groups +/- resistance training, measured by with ultrasound, Keiser leg press machine and IMVC using isokinetic dynamometry

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Norges Idrettshoegskole

Sponsor organisation

Norges Idrettshoegskole

Address

Sognsveien 220

City

Oslo

Postcode

0863

Country

Norway

Scientific contact point

Organisation

Norges Idrettshoegskole

Contact name

Daniel Tømmerbakke

Public contact point

Organisation

Norges Idrettshoegskole

Contact name

Daniel Tømmerbakke

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 29 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications