A single-center, double-blind, randomized, placebo-controlled, two-arm study to evaluate the safety and efficacy of once-weekly sirolimus (rapamycin) on muscle strength and endurance in older adults following a 13-week exercise program.
Humans
Double-Blind Method
Sirolimus
/ administration & dosage
Aged
Muscle Strength
/ drug effects
Aged, 80 and over
Male
Female
Physical Endurance
/ drug effects
Randomized Controlled Trials as Topic
Drug Administration Schedule
Treatment Outcome
MTOR Inhibitors
/ administration & dosage
Muscle, Skeletal
/ drug effects
Exercise Therapy
/ methods
Quality of Life
Time Factors
Aging
Exercise
Muscle endurance
Muscle strength
Older adults
Randomized controlled trial
Rapamycin
Sarcopenia
Sirolimus
mTOR
Journal
Trials
ISSN: 1745-6215
Titre abrégé: Trials
Pays: England
ID NLM: 101263253
Informations de publication
Date de publication:
01 Oct 2024
01 Oct 2024
Historique:
received:
17
07
2024
accepted:
20
09
2024
medline:
2
10
2024
pubmed:
2
10
2024
entrez:
1
10
2024
Statut:
epublish
Résumé
Aging leads to a decline in muscle mass and strength, contributing to frailty and decreased quality of life. Sirolimus (rapamycin) , an mTOR inhibitor, has shown potential in preclinical studies to extend lifespan and improve health span. This study evaluates the safety and efficacy of once-weekly sirolimus (rapamycin) administration on muscle strength and endurance in older adults engaged in a 13-week exercise program. This randomized, double-blind, placebo-controlled trial will enroll 40 participants aged 65-85. Participants will be randomly assigned to receive either sirolimus (rapamycin) 6 mg/week or placebo for 13 weeks, in conjunction with an at-home exercise program. The primary outcome measure is the change in muscle strength and endurance, assessed by the 30-Second Chair-Stand Test. Secondary outcome measures include adverse events, changes in muscle strength and endurance as measured by the 6-min walk test, handgrip strength, and participant-reported outcomes using the SF-36 survey. Assessments will be conducted at baseline, mid-intervention (week 6), and post-intervention (week 13). Blood samples will be collected for hematology and biochemistry analyses, including full blood count, urea and electrolytes, liver function tests, HbA1c, lipids, serum IGF-1, and hs-CRP. DNA methylation will be analyzed using TruDiagnostic™ to explore changes in biological age. This study aims to provide insights into the potential benefits of intermittent sirolimus (rapamycin) administration on muscle performance in older adults. By alternating periods of mTOR inhibition through rapamycin and activation via exercise, this study will explore a novel approach to enhancing muscle strength and endurance in the aging population. The results could have significant implications for developing interventions to improve physical function and overall health outcomes in older adults. Safety and tolerability will also be closely monitored to ensure the feasibility of this regimen for wider application. Australia New Zealand Clinical Trials Registry, ACTRN12624000790549. Registered on 26 June 2024 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12624000790549 .
Sections du résumé
BACKGROUND
BACKGROUND
Aging leads to a decline in muscle mass and strength, contributing to frailty and decreased quality of life. Sirolimus (rapamycin) , an mTOR inhibitor, has shown potential in preclinical studies to extend lifespan and improve health span. This study evaluates the safety and efficacy of once-weekly sirolimus (rapamycin) administration on muscle strength and endurance in older adults engaged in a 13-week exercise program.
METHODS
METHODS
This randomized, double-blind, placebo-controlled trial will enroll 40 participants aged 65-85. Participants will be randomly assigned to receive either sirolimus (rapamycin) 6 mg/week or placebo for 13 weeks, in conjunction with an at-home exercise program. The primary outcome measure is the change in muscle strength and endurance, assessed by the 30-Second Chair-Stand Test. Secondary outcome measures include adverse events, changes in muscle strength and endurance as measured by the 6-min walk test, handgrip strength, and participant-reported outcomes using the SF-36 survey. Assessments will be conducted at baseline, mid-intervention (week 6), and post-intervention (week 13). Blood samples will be collected for hematology and biochemistry analyses, including full blood count, urea and electrolytes, liver function tests, HbA1c, lipids, serum IGF-1, and hs-CRP. DNA methylation will be analyzed using TruDiagnostic™ to explore changes in biological age.
DISCUSSION
CONCLUSIONS
This study aims to provide insights into the potential benefits of intermittent sirolimus (rapamycin) administration on muscle performance in older adults. By alternating periods of mTOR inhibition through rapamycin and activation via exercise, this study will explore a novel approach to enhancing muscle strength and endurance in the aging population. The results could have significant implications for developing interventions to improve physical function and overall health outcomes in older adults. Safety and tolerability will also be closely monitored to ensure the feasibility of this regimen for wider application.
TRIAL REGISTRATION
BACKGROUND
Australia New Zealand Clinical Trials Registry, ACTRN12624000790549. Registered on 26 June 2024 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12624000790549 .
Identifiants
pubmed: 39354527
doi: 10.1186/s13063-024-08490-2
pii: 10.1186/s13063-024-08490-2
doi:
Substances chimiques
Sirolimus
W36ZG6FT64
MTOR Inhibitors
0
Types de publication
Journal Article
Clinical Trial Protocol
Langues
eng
Sous-ensembles de citation
IM
Pagination
642Informations de copyright
© 2024. The Author(s).
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