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Lysosomal Movement and Anabolic Resistance

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03032757
Recruitment Status : Unknown
Verified October 2017 by William Apro, University of Birmingham.
Recruitment status was:  Recruiting
First Posted : January 26, 2017
Last Update Posted : October 25, 2017
Sponsor:
Information provided by (Responsible Party):
William Apro, University of Birmingham

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Sarcopenia Dietary Supplement: Essential amino acids Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 26 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Defining the Role of Lysosomal Movement in Age-associated Anabolic Resistance in Human Skeletal Muscle
Actual Study Start Date : May 12, 2017
Estimated Primary Completion Date : August 30, 2018
Estimated Study Completion Date : August 30, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Resting leg of young males Dietary Supplement: Essential amino acids
240 mg essential amino acids per kg body weight dissolved in 500 ml of water provided after exercise.

Experimental: Exercising leg of young males Dietary Supplement: Essential amino acids
240 mg essential amino acids per kg body weight dissolved in 500 ml of water provided after exercise.

Experimental: Resting leg of elderly males Dietary Supplement: Essential amino acids
240 mg essential amino acids per kg body weight dissolved in 500 ml of water provided after exercise.

Experimental: Exercising leg of elderly males Dietary Supplement: Essential amino acids
240 mg essential amino acids per kg body weight dissolved in 500 ml of water provided after exercise.




Primary Outcome Measures :
  1. Lysosomal movement [ Time Frame: ~360 minutes ]
    Changes in intracellular localization of lysosomes will be measured via immunofluorescence


Secondary Outcome Measures :
  1. Lysosomal movement in isolated muscle cells [ Time Frame: ~30 minutes ]
    Changes in intracellular localization of lysosomes will be measured via immunofluorescence



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03032757


Contacts
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Contact: William Apro, Ph.D. 01214142875 w.apro@bham.ac.uk
Contact: Andrew Philp, Ph.D. 0121414 8872 a.philp@bham.ac.uk

Locations
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United Kingdom
School of Sport, Exercise and Rehabilitation Sciences at University of Birmingham Recruiting
Birmingham, West Midlands, United Kingdom, B152TT
Contact: William Apro, Ph.D.    0121 414 2875    w.apro@bham.ac.uk   
Sponsors and Collaborators
University of Birmingham
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Responsible Party: William Apro, Ph.D., University of Birmingham
ClinicalTrials.gov Identifier: NCT03032757    
Other Study ID Numbers: RG_16-200
First Posted: January 26, 2017    Key Record Dates
Last Update Posted: October 25, 2017
Last Verified: October 2017

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Sarcopenia
Muscular Atrophy
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Atrophy
Pathological Conditions, Anatomical