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Trial record 1 of 5 for:    volpi | Sarcopenia
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Identifying Therapeutic Targets of Accelerated Sarcopenia

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ClinicalTrials.gov Identifier: NCT03118050
Recruitment Status : Recruiting
First Posted : April 18, 2017
Last Update Posted : December 19, 2019
Sponsor:
Collaborator:
National Institute on Aging (NIA)
Information provided by (Responsible Party):
The University of Texas Medical Branch, Galveston

Brief Summary:
The proposed research is designed to identify the mechanisms that can accelerate loss of muscle size, strength and physical function in type 2 diabetes and with hospitalization in older persons. About ⅓ of older Americans have type 2 diabetes, and about ⅓ of the hospitalizations in the USA involve persons older than 65 year of age. The proposed research is relevant to the part of NIH's mission that pertains to development of the fundamental knowledge that will improve health and reduce the burdens of disability, because this work will provide the fundamental evidence to identify new targets for the development of innovative treatments to slow down muscle loss and disability in our aging society.

Condition or disease Intervention/treatment Phase
Sarcopenia Diabetes Mellitus Aging Behavioral: Resistance exercise training Behavioral: Bed rest Behavioral: Intensive physical therapy Not Applicable

Detailed Description:
Sarcopenia is a major contributor to frailty and increases the risk of falls, physical dependence, disability and mortality in older adults. It advances slowly with healthy aging. However, diseases or other insults and injuries can accelerate sarcopenia and lead to catastrophic declines in mobility and independence. For example, chronic diseases such as Type 2 Diabetes Mellitus (T2DM) are associated with accelerated loss of muscle mass and function in seniors; hospitalization with bed rest inactivity acutely accelerates sarcopenia. What it is not know is how concurrent diseases, inactivity or other insults and injuries accelerate sarcopenia in older adults. This knowledge gap hinders the development of innovative, targeted treatments for this disabling condition. The objective of this research is to examine the basic mechanisms that underlie accelerated sarcopenia in older adults and identify potential targets for interventions. The central hypothesis is that a global and fundamental mechanism of acute or chronic acceleration of sarcopenia is a reduction in skeletal muscle amino acid transport, which decreases muscle protein anabolism, and can be reversed by activation of the mammalian/mechanistic Target of Rapamycin Complex 1 (mTORC1) signaling with a non-amino acid stimulus, such as exercise. Amino acid transport is an active process that controls intracellular amino acid availability and the activation of protein synthesis in skeletal muscle. It is regulated by amino acid concentrations and non-amino acid stimuli that activate mTORC1 signaling, such as resistance exercise and insulin.The central hypothesis will be tested with the following specific aims: 1) Determine the effect of T2DM on the sensitivity of skeletal muscle amino acid transport to dietary amino acids. 2) Determine the effect of short-term bed rest inactivity on the sensitivity of skeletal muscle amino acid transport to dietary amino acids. 3) Determine the effect of resistance exercise on the sensitivity of amino acid transport to dietary amino acids in acute and chronic accelerated sarcopenia induced by inactivity or T2DM. Amino acid transport and protein metabolism in muscle will be measured using integrative molecular, imaging and stable isotope methodologies, identifying specific upstream regulators involved in the anabolic resistance of accelerated sarcopenia that can be targeted with novel treatments to reduce sarcopenia and improve independence in older adults.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 102 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Basic Science
Official Title: Identifying Therapeutic Targets of Accelerated Sarcopenia
Actual Study Start Date : May 28, 2017
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2025

Arm Intervention/treatment
Experimental: RT in T2DM
Type 2 diabetes subjects will undergo 3 months of resistance exercise training. Muscle size, strength and response to a low dose amino acids will be measured before and after training.
Behavioral: Resistance exercise training
Supervised resistance exercise training, 3 times a week for 3 months
Other Name: RT

Experimental: BR in healthy subjects, LAA
Healthy subjects will undergo short term bed rest with standard of care physical therapy. Muscle size, strength and response to a low dose amino acids (LAA) will be measured before and after bed rest.
Behavioral: Bed rest
Bed rest for 5 days, followed by standard rehabilitation for 2 days
Other Name: BR

Experimental: BR in healthy subjects, HAA
Healthy subjects will undergo short term bed rest with standard of care physical therapy. Muscle size, strength and response to a high dose amino acids (HAA) will be measured before and after bed rest.
Behavioral: Bed rest
Bed rest for 5 days, followed by standard rehabilitation for 2 days
Other Name: BR

Experimental: BR in T2DM, LAA
Type 2 diabetes (T2DM) subjects will undergo short term bed rest with standard of care physical therapy. Muscle size, strength and response to a low dose amino acids (LAA) will be measured before and after bed rest.
Behavioral: Bed rest
Bed rest for 5 days, followed by standard rehabilitation for 2 days
Other Name: BR

Experimental: BR in T2DM, HAA
Type 2 diabetes (T2DM) subjects will undergo short term bed rest with standard of care physical therapy. Muscle size, strength and response to a high dose amino acids (HAA) will be measured before and after bed rest.
Behavioral: Bed rest
Bed rest for 5 days, followed by standard rehabilitation for 2 days
Other Name: BR

Experimental: BR in healthy subjects, PT
Healthy subjects will undergo short term bed rest with intensive physical therapy (PT). Muscle size, strength and response to a low dose amino acids (LAA) will be measured before and after bed rest.
Behavioral: Bed rest
Bed rest for 5 days, followed by standard rehabilitation for 2 days
Other Name: BR

Behavioral: Intensive physical therapy
Intensive weight bearing PT, daily, during bed rest
Other Name: PT

Experimental: BR in T2DM, PT
Type 2 diabetes (T2DM) subjects will undergo short term bed rest with intensive physical therapy (PT). Muscle size, strength and response to a low dose amino acids (LAA) will be measured before and after bed rest.
Behavioral: Bed rest
Bed rest for 5 days, followed by standard rehabilitation for 2 days
Other Name: BR

Behavioral: Intensive physical therapy
Intensive weight bearing PT, daily, during bed rest
Other Name: PT




Primary Outcome Measures :
  1. Amino acid transporter expression [ Time Frame: Change from baseline to up to 3 months ]
    Measurement of change in amino acid transporter expression


Secondary Outcome Measures :
  1. Leg lean mass [ Time Frame: Change from baseline to up to 3 months ]
    Measurement of change in leg lean mass by DEXA

  2. Knee extension strength [ Time Frame: Change from baseline to up to 3 months ]
    Measurement of change in maximum strength by standard method

  3. Muscle protein synthesis [ Time Frame: Change from baseline to up to 3 months ]
    Measurement of change in muscle protein synthesis by standard stable isotope methodology



Information from the National Library of Medicine

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Ages Eligible for Study:   60 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Body mass index: <40 kg/sq meter
  • Score ≥26 on the 30-item Mini Mental State Examination
  • Stable body weight for at least 3 months
  • Non-diabetic or with Type 2 Diabetes Mellitus

Exclusion Criteria:

  • Pre-diabetes per American Diabetes Association criteria
  • Insulin therapy, significant diabetic complications, or A1c>8%
  • Impairment in Activities of Daily Living
  • >2 falls/year
  • weight loss >5% in the past 6 months
  • Exercise training (≥2 sessions/week) or ≥10,000 steps/day
  • Significant cardiovascular, liver, renal, blood, or respiratory disease
  • Active cancer or infection
  • Recent (within 3 months) treatment with anabolic steroids, systemic corticosteroids or estrogen.
  • Alcohol or drug abuse

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): NCT03118050


Contacts
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Contact: Roxana M Hirst, MS, CCRP (409)266-9641 rmhirst@utmb.edu
Contact: Paula Skinkis, MEd pskinkis@utmb.edu

Locations
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United States, Texas
Sealy Center on Aging, University of Texas Medical Branch Recruiting
Galveston, Texas, United States, 77550
Contact: Roxana Hirst, MS, CCRP    409-266-9641    rmhirst@utmb.edu   
Contact: Paula Skinkis, MEd, CCRP    (409)772-1907    pskinkis@utmb.edu   
Principal Investigator: Elena Volpi, MD, PhD         
Sponsors and Collaborators
The University of Texas Medical Branch, Galveston
National Institute on Aging (NIA)
Investigators
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Principal Investigator: Elena Volpi, MD, PhD UTMB

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Responsible Party: The University of Texas Medical Branch, Galveston
ClinicalTrials.gov Identifier: NCT03118050    
Other Study ID Numbers: 15-0229
R01AG049611 ( U.S. NIH Grant/Contract )
First Posted: April 18, 2017    Key Record Dates
Last Update Posted: December 19, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Small physiological study. Few subjects. Risk of loss of confidentiality

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by The University of Texas Medical Branch, Galveston:
exercise
bed rest
muscle
nutrition
amino acids
Additional relevant MeSH terms:
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Sarcopenia
Muscular Atrophy
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Atrophy
Pathological Conditions, Anatomical
Signs and Symptoms