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

• Status: Recruiting
• Trial end date: 2024-05-01
• Target enrollment: 0
• Participant gender: Male

Summary

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.

• Phase: N/A
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Nottingham
• Collaborator: University of Oxford
• Treatments: Sirolimus

Criteria

Inclusion Criteria:

• Participant is willing and able to give informed consent for participation in the study

• Participant is physically able to complete the resistance exercise training programme

Exclusion Criteria:

• • A BMI <18 or >35 kg/m2

• Active cardiovascular, cerebrovascular or respiratory disease: e.g. uncontrolled hypertension (BP > 160/100), angina, heart failure (class III/IV), arrhythmia, right to left cardiac shunt, recent cardiac event, COPD, pulmonary hypertension or recent stroke

• Any metabolic disease

• Clotting dysfunction

• A history of, or current neurological or musculoskeletal conditions (e.g. epilepsy)

• Having taken part in a research study in the last 3 months involving invasive procedures or an inconvenience allowance (this must remain for ALL UoN FMHS UREC approved studies)

• Contraindications to MRI scanning including claustrophobia, pacemaker, metal implants etc. which will be assessed through an MRI safety screening questionnaire.

• Contraindications to the use of Rapamycin e.g. those due scheduled vaccinations (as rapamycin can reduce the efficacy of vaccines).