Lysosomal Movement and Anabolic Resistance

NCT ID: NCT03032757

Last Updated: 2017-10-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

26 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-05-12

Study Completion Date

2018-08-30

Brief Summary

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Age-associated loss of muscle mass, termed sarcopenia, is strongly associated with functional impairment and physical disability in the elderly. Maintenance or growth of muscle mass is mainly driven by increased muscle protein synthesis (i.e. the generation of new muscle protein) in response to exercise and feeding. However, several investigations have shown that elderly individuals have a blunted protein synthetic response following protein intake. This inability of the elderly to properly respond to growth stimuli has been termed anabolic resistance and plays a significant role in the development of sarcopenia. However, the precise mechanisms underpinning anabolic resistance are unknown.

It is well established that muscle protein synthesis at the molecular level is regulated by a cellular protein complex called mTORC1. When exposed to a growth stimulus, mTORC1 has been shown to associate with lysosomes, i.e. the intracellular organelles responsible for the breakdown of cellular proteins, and subsequently moving towards the cell periphery.

This movement of lysosome-associated mTORC1 within the cell is believed to be vital for the activation of protein synthesis, as inhibition of lysosomal movement blunts mTORC1 activation in response to amino acids. Thus, dysregulation of lysosomal movement in ageing muscle may represent an underlying mechanism in the development of anabolic resistance. However, this area of research is unexplored in the context of human skeletal muscle. The investigators hypothesize that dysregulation of lysosomal movement plays a central role in the development of age-associated skeletal muscle anabolic resistance.

Detailed Description

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Conditions

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Sarcopenia

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Resting leg of young males

Group Type EXPERIMENTAL

Essential amino acids

Intervention Type DIETARY_SUPPLEMENT

240 mg essential amino acids per kg body weight dissolved in 500 ml of water provided after exercise.

Exercising leg of young males

Group Type EXPERIMENTAL

Essential amino acids

Intervention Type DIETARY_SUPPLEMENT

240 mg essential amino acids per kg body weight dissolved in 500 ml of water provided after exercise.

Resting leg of elderly males

Group Type EXPERIMENTAL

Essential amino acids

Intervention Type DIETARY_SUPPLEMENT

240 mg essential amino acids per kg body weight dissolved in 500 ml of water provided after exercise.

Exercising leg of elderly males

Group Type EXPERIMENTAL

Essential amino acids

Intervention Type DIETARY_SUPPLEMENT

240 mg essential amino acids per kg body weight dissolved in 500 ml of water provided after exercise.

Interventions

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Essential amino acids

240 mg essential amino acids per kg body weight dissolved in 500 ml of water provided after exercise.

Intervention Type DIETARY_SUPPLEMENT

Eligibility Criteria

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Inclusion Criteria

Be a non-smoking male within the specified age range for each group (young; 18-35 yrs, old; 65-75 yrs)

Have a BMI (body mass index, body weight/height in m2) between 18 and 25 kg/m2, which is considered a normal body mass index.

Be in good general health: no cardiovascular diseases or metabolic diseases.

Exclusion Criteria

Health problems such as: heart disease , metabolic disease such as phenylketonuria, rheumatoid arthritis, uncontrolled hypertension, poor lung function, or any health condition that might put the participant at risk when participating in this study.

Generalized neuromuscular disease (such as Parkinson's disease or motorneuron disease).

Involvement in regular structured resistance exercise training at the time of the study.

Consumption of any analgesic drugs, anti-inflammatory drugs, or medication that is known to affect protein metabolism (beta-blockers, corticosteroids, NSAIDs).

Participants who have undergone muscle biopsy testing or isotope infusion procedures within the last 5 years.

Allergic to lidocaine
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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University of Birmingham

OTHER

Sponsor Role lead

Responsible Party

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William Apro

Ph.D.

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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School of Sport, Exercise and Rehabilitation Sciences at University of Birmingham

Birmingham, West Midlands, United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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William Apro, Ph.D.

Role: CONTACT

Phone: 01214142875

Email: [email protected]

Andrew Philp, Ph.D.

Role: CONTACT

Phone: 0121414 8872

Email: [email protected]

Facility Contacts

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William Apro, Ph.D.

Role: primary

Other Identifiers

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RG_16-200

Identifier Type: -

Identifier Source: org_study_id