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

NCT05414292 | Recruiting

• 1 other identifier: Rapamune_COMAP
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Muscle Atrophy; Age-Related Sarcopenia

Outcome Measures

Primary Outcomes (3)

• Change in muscle mass from baseline

  To determine the impacts of rapamycin, an mTOR inhibitor, on human muscle mass through whole body muscle mass measures by MRI and D3 creatine tracer, and ultrasound of the thigh muscles.

  0 and 16 weeks

• Change in muscle mass from baseline

  To determine the impacts of rapamycin, an mTOR inhibitor, on human muscle mass through whole body muscle mass measures by MRI and D3 creatine tracer, and ultrasound of the thigh muscles.

  0 and 8 weeks

• Change in muscle mass from baseline

  To determine the impacts of rapamycin, an mTOR inhibitor, on human muscle mass through whole body muscle mass measures by MRI and D3 creatine tracer, and ultrasound of the thigh muscles.

  0 and 5 weeks

Secondary Outcomes (7)

• Change in muscle strength

  0, 5, 8 and 16 weeks

• Change in muscle power

  0, 5, 8 and 16 weeks

• Change in muscle function

  0, 5, 8 and 16 weeks

• Change in neuromuscular function

  0, 5, 8 and 16 weeks

• Change in Muscle Protein Synthesis

  2, 5, and 8 weeks

Study Arms (2)

Drug group

EXPERIMENTAL

Will take 1mg Rapamune (sirolimus) in oral tablet form daily for 16 weeks.

Drug: Rapamune (sirolimus) 1Mg Tablet; Behavioral: Unilateral resistance exercise training

Placebo group

PLACEBO COMPARATOR

Will take a placebo tablet (lactose) daily for 16 weeks

Behavioral: Unilateral resistance exercise training

Interventions

Rapamune (sirolimus) 1Mg Tablet DRUG

Take Rapamune to see the effect on muscle structure and function during a 14 week unilateral resistance exercise training programme.

Also known as: Rapamycin, Sirolimus, Rapamune

Drug group

Unilateral resistance exercise training BEHAVIORAL

Participants will complete unilateral leg extension resistance training 3 times per week for 14 weeks at 75% of their 1 repetition maximum

Also known as: Leg extension, Strength training

Drug group; Placebo group

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of Nottingham: lead
• University of Oxford: collaborator

Study Sites (1)

University of Nottingham School of Medicine

Derby, DE22 3DT, United Kingdom

RECRUITING

MeSH Terms

Conditions

Muscular Atrophy

Interventions

Sirolimus; Tablets; Resistance Training

Condition Hierarchy (Ancestors)

Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Dosage Forms; Pharmaceutical Preparations; Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Physical Therapy Modalities; Physical Conditioning, Human; Exercise; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Central Study Contacts

Philip Atherton, PhD

CONTACT

01332724725; philip.atherton@nottingham.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Participant will not know if they are taking Rapamune or placebo
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 30, 2022
• First Posted: June 10, 2022
• Study Start: August 6, 2021
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: April 10, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ANALYTIC CODE
• Time Frame: The data will be available on conclusion of the study.
• Access Criteria: Listed collaborators will have access on request with data given on approval by the principal investigator

Locations

GB (1)