NCT05414292: Rapamune

Impacts of Mechanistic Target of Rapamycin (mTOR) Inhibition on Aged Human Muscle (Rapamune)

Recruiting now NA Last updated 10 April 2025

What this trial tests

NA trial testing Rapamune (sirolimus) 1Mg Tablet in Muscle Atrophy in 16 participants. Currently enrolling.

Timeline

6 August 2021

Primary endpoint
1 May 2027

1 May 2027

Quick facts

Lead sponsor	University of Nottingham
Phase	NA
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	single
Primary purpose	health services research
Enrollment	16
Start date	6 August 2021
Primary completion	1 May 2027
Estimated completion	1 May 2027
Sites	1 location across United Kingdom

Drugs / interventions tested

• Rapamune (sirolimus) 1Mg Tablet — full drug profile →
• Unilateral resistance exercise training

Conditions studied

• Muscle Atrophy — all drugs for Muscle Atrophy →
• Age-Related Sarcopenia — all drugs for Age-Related Sarcopenia →

Sponsor

University of Nottingham

Who can join

Adults 50 to 90, male only, with Muscle Atrophy or Age-Related Sarcopenia. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

As people age, muscle mass and function is lost and exercise training is an important way to reduce the effects of this and remain independent. However, not everyone can perform this exercise and the muscle responses to exercise are often reduced in older people. So far there has been no drug found to specifically treat or reduce this problem.

Muscle size depends on the balance of muscle protein breakdown and synthesis (building). This balance is regulated by multiple signals within the body, but a particular molecule - the mechanistic target of rapamycin (mTOR), is known to play an important role. For protein synthesis to build up the muscles, this pathway is needed to start the process when triggered by eating protein or exercise. Although this would suggest that mTOR activity is good, excessive levels of this signalling seem to have negative impacts on muscle maintenance with age.

In animal studies, blocking mTOR signalling has stopped the development of a number of age-related diseases and increased health-span. Drugs that block this pathway (e.g. Rapamune) reduce the stimulation of muscle protein synthesis, possibly through changing the immune system, but conversely have also been shown to increase muscle size and reduce markers of nerve supply loss. This means that drugs which block the mTOR pathway could, in older people, help to reduce the negative impacts of excessive mTOR signalling on muscle size and function.

The investigators aim to recruit 16 healthy male volunteers over 50 years old to investigate how the drug Rapamune (which blocks the mTOR pathway) affects aged human muscle both on its own and when combined with resistance exercise training.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Blazing a trail for the clinical use of rapamycin as a geroprotecTOR.
   Konopka AR, Lamming DW, RAP PAC Investigators, EVERLAST Investigators. · · 2023 · cited 33× · PMID 37801202 · DOI 10.1007/s11357-023-00935-x
2. Antiaging Strategies and Remedies: A Landscape of Research Progress and Promise.
   Tenchov R, Sasso JM, Wang X, Zhou QA. · · 2024 · cited 23× · PMID 38214973 · DOI 10.1021/acschemneuro.3c00532
3. Sarcopenia in chronic kidney disease: from bench to bedside.
   Kim DW, Song SH. · · 2023 · cited 18× · PMID 37077132 · DOI 10.3904/kjim.2022.338
4. Geroprotector drugs and exercise: friends or foes on healthy longevity?
   Elliehausen CJ, Anderson RM, Diffee GM, Rhoads TW, et al · · 2023 · cited 17× · PMID 38066609 · DOI 10.1186/s12915-023-01779-9
5. Targeting Crosstalk of Signaling Pathways among Muscles-Bone-Adipose Tissue: A Promising Therapeutic Approach for Sarcopenia.
   Sharma AR, Chatterjee S, Lee YH, Lee SS. · · 2024 · cited 10× · PMID 37815907 · DOI 10.14336/ad.2023.00903
6. Effect of Cellular Senescence in Disease Progression and Transplantation: Immune Cells and Solid Organs.
   Kirchner VA, Badshah JS, Hong SK, Martinez O, et al · · 2024 · cited 8× · PMID 37953486 · DOI 10.1097/tp.0000000000004838
7. Rapamycin Exerts Its Geroprotective Effects in the Ageing Human Immune System by Enhancing Resilience Against DNA Damage.
   Kell L, Jones EJ, Gharahdaghi N, Wilkinson DJ, et al · · 2026 · cited 3× · PMID 41524558 · DOI 10.1111/acel.70364
8. Functional Features of Senescent Cells and Implications for Therapy.
   Kirichenko TV, Markina YV, Markin AM, Vasilyev VS, et al · · 2025 · cited 2× · PMID 40508198 · DOI 10.3390/ijms26115390