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| ID | Type | Description | Link |
|---|---|---|---|
| R01AG049611 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Aging (NIA) | NIH |
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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.
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 known 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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| RT in T2DM | Experimental | 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. Results of this arm will be compared to those previously obtained in healthy older subjects who participated in NCT02999802 (same training protocol) after 1:1 matching for age and sex. |
|
| BR in healthy subjects, LAA | Experimental | 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. |
|
| BR in healthy subjects, HAA | Experimental | 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. |
|
| BR in T2DM, LAA | Experimental | 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. |
|
| BR in T2DM, HAA |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Resistance exercise training | Behavioral | Supervised resistance exercise training, 3 times a week for 3 months |
|
| Measure | Description | Time Frame |
|---|---|---|
| Leg Lean Mass | Measurement of change in leg lean mass by DEXA | Change from baseline to up to 3 months |
| Measure | Description | Time Frame |
|---|---|---|
| Knee Extension Strength | Measurement of change in maximum strength by standard method | Change from baseline to up to 3 months |
| Measure | Description | Time Frame |
|---|---|---|
| Amino Acid Transporter Expression | Measurement of change in amino acid transporter expression | Change from baseline to up to 3 months |
| Muscle Protein Synthesis | Measurement of change in muscle protein synthesis by standard stable isotope methodology |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Elena Volpi, MD, PhD | UTMB | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sealy Center on Aging, University of Texas Medical Branch | Galveston | Texas | 77550 | United States |
Small physiological study. Few subjects. Risk of loss of confidentiality
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Eligible participants were randomized to one of six bed rest (BR) study arms under IRB protocol 17-0064. Separately, eligible participants were randomized to one of six resistance training (RT) study arms under IRB protocol 15-0229. The RT data were analyzed in comparison with de-identified data obtained from NTC02999802.
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| ID | Title | Description |
|---|---|---|
| FG000 | Resistance Training in Type 2 Diabetes (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. Results of this arm will be compared to those previously obtained in healthy older subjects who participated in NCT02999802 (same training protocol) after 1:1 matching for age and sex. Resistance exercise training: Supervised resistance exercise training, 3 times a week for 3 months |
| FG001 | Bed Rest in Healthy Subjects, Low-dose Amino Acids (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. Bed rest: Bed rest for 5 days, followed by standard rehabilitation for 2 days. UTMB IRB 17-0064 |
| FG002 | Bed Rest in Healthy Subjects, High-dose Amino Acids (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. Bed rest: Bed rest for 5 days, followed by standard rehabilitation for 2 days. UTMB IRB 17-0064 |
| FG003 | Bed Rest in Type 2 Diabetes (T2DM), Low-dose Amino Acids (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. Bed rest: Bed rest for 5 days, followed by standard rehabilitation for 2 days |
| FG004 | Bed Rest in Type 2 Diabetes (T2DM), High-dose Amino Acids (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. Bed rest: Bed rest for 5 days, followed by standard rehabilitation for 2 days |
| FG005 | Bed Rest in Healthy Subjects, Physical Therapy (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. Bed rest: Bed rest for 5 days, followed by standard rehabilitation for 2 days Intensive physical therapy: Intensive weight bearing PT, daily, during bed rest. UTMB IRB 17-0064 |
| FG006 | 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. Bed rest: Bed rest for 5 days, followed by standard rehabilitation for 2 days Intensive physical therapy: Intensive weight bearing PT, daily, during bed rest. UTMB IRB 17-0064 |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Resistance Training in Type 2 Diabetes (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. Results of this arm will be compared to those previously obtained in healthy older subjects who participated in NCT02999802 (same training protocol) after 1:1 matching for age and sex. Resistance exercise training: Supervised resistance exercise training, 3 times a week for 3 months |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Leg Lean Mass | Measurement of change in leg lean mass by DEXA | Posted | Mean | Standard Deviation | kg | Change from baseline to up to 3 months |
|
Adverse events were monitored from baseline through 1 week following completion of the intervention period.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Resistance Training in Type 2 Diabetes (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. Results of this arm will be compared to those previously obtained in healthy older subjects who participated in NCT02999802 (same training protocol) after 1:1 matching for age and sex. Resistance exercise training: Supervised resistance exercise training, 3 times a week for 3 months |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Home medication error | Vascular disorders | Systematic Assessment | The participant accidentally took a double dose of prescribed blood pressure medication. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Elena Volpi, MD, PhD | University of Texas Medical Branch | 210-562-6139 | volpi@uthscsa.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol: 15-0229 Study Protocol | Feb 4, 2019 | Oct 29, 2025 | Prot_000.pdf |
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan: 17-0064 Study Protocol | Jan 25, 2023 | Nov 20, 2025 | Prot_SAP_001.pdf |
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| ID | Term |
|---|---|
| D055948 | Sarcopenia |
| D003920 | Diabetes Mellitus |
| D009043 | Motor Activity |
| ID | Term |
|---|---|
| D009133 | Muscular Atrophy |
| D020879 | Neuromuscular Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D055070 | Resistance Training |
| D001510 | Bed Rest |
| ID | Term |
|---|---|
| D005081 | Exercise Therapy |
| D012046 | Rehabilitation |
| D000359 | Aftercare |
| D003266 | Continuity of Patient Care |
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| Experimental |
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. |
|
| BR in healthy subjects, PT | Experimental | 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. |
|
| BR in T2DM, PT | Experimental | 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. |
|
| Bed rest | Behavioral | Bed rest for 5 days, followed by standard rehabilitation for 2 days |
|
|
| Intensive physical therapy | Behavioral | Intensive weight bearing PT, daily, during bed rest |
|
|
| Change from baseline to up to 3 months |
| BG001 | Bed Rest in Healthy Subjects, Low-dose Amino Acids (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. Bed rest: Bed rest for 5 days, followed by standard rehabilitation for 2 days. UTMB IRB 17-0064 |
| BG002 | Bed Rest in Healthy Subjects, High-dose Amino Acids (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. Bed rest: Bed rest for 5 days, followed by standard rehabilitation for 2 days. UTMB IRB 17-0064 |
| BG003 | Bed Rest in Type 2 Diabetes (T2DM), Low-dose Amino Acids (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. Bed rest: Bed rest for 5 days, followed by standard rehabilitation for 2 days. UTMB IRB 17-0064 |
| BG004 | Bed Rest in Type 2 Diabetes (T2DM), High-dose Amino Acids (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. Bed rest: Bed rest for 5 days, followed by standard rehabilitation for 2 days. UTMB IRB 17-0064 |
| BG005 | Bed Rest in Healthy Subjects, Physical Therapy (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. Bed rest: Bed rest for 5 days, followed by standard rehabilitation for 2 days Intensive physical therapy: Intensive weight bearing PT, daily, during bed rest. UTMB IRB 17-0064 |
| BG006 | Bed Rest in Type 2 Diabetes (T2DM), Physical Therapy (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. Bed rest: Bed rest for 5 days, followed by standard rehabilitation for 2 days Intensive physical therapy: Intensive weight bearing PT, daily, during bed rest. UTMB IRB 17-0064 |
| BG007 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
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.
Bed rest: Bed rest for 5 days, followed by standard rehabilitation for 2 days. UTMB IRB 17-0064
| OG002 | Bed Rest in Healthy Subjects, High-dose Amino Acids (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. Bed rest: Bed rest for 5 days, followed by standard rehabilitation for 2 days. UTMB IRB 17-0064 |
| OG003 | Bed Rest in Type 2 Diabetes (T2DM), Low-dose Amino Acids (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. Bed rest: Bed rest for 5 days, followed by standard rehabilitation for 2 days. UTMB IRB 17-0064 |
| OG004 | Bed Rest in Type 2 Diabetes (T2DM), High-dose Amino Acids (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. Bed rest: Bed rest for 5 days, followed by standard rehabilitation for 2 days. UTMB IRB 17-0064 |
| OG005 | Bed Rest in Healthy Subjects, Physical Therapy (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. Bed rest: Bed rest for 5 days, followed by standard rehabilitation for 2 days Intensive physical therapy: Intensive weight bearing PT, daily, during bed rest. UTMB IRB 17-0064 |
| OG006 | Bed Rest in Type 2 Diabetes (T2DM), Physical Therapy (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. Bed rest: Bed rest for 5 days, followed by standard rehabilitation for 2 days Intensive physical therapy: Intensive weight bearing PT, daily, during bed rest. UTMB 17-0064 |
|
|
|
| Secondary | Knee Extension Strength | Measurement of change in maximum strength by standard method | Posted | Mean | Standard Deviation | Nm | Change from baseline to up to 3 months |
|
|
|
|
| Other Pre-specified | Amino Acid Transporter Expression | Measurement of change in amino acid transporter expression | Not Posted | Oct 2026 | Change from baseline to up to 3 months | Participants |
| Other Pre-specified | Muscle Protein Synthesis | Measurement of change in muscle protein synthesis by standard stable isotope methodology | Not Posted | Change from baseline to up to 3 months | Participants |
| 0 |
| 15 |
| 0 |
| 15 |
| 0 |
| 15 |
| EG001 | Bed Rest in Healthy Subjects, Low-dose Amino Acids (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. Bed rest: Bed rest for 5 days, followed by standard rehabilitation for 2 days. UTMB IRB 17-0064 | 0 | 7 | 0 | 7 | 0 | 7 |
| EG002 | Bed Rest in Healthy Subjects, High-dose Amino Acids (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. Bed rest: Bed rest for 5 days, followed by standard rehabilitation for 2 days. UTMB IRB 17-0064 | 1 | 5 | 0 | 5 | 0 | 5 |
| EG003 | Bed Rest in Type 2 Diabetes (T2DM), Low-dose Amino Acids (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. Bed rest: Bed rest for 5 days, followed by standard rehabilitation for 2 days. UTMB IRB 17-0064 | 0 | 6 | 0 | 6 | 0 | 6 |
| EG004 | Bed Rest in Type 2 Diabetes (T2DM), High-dose Amino Acids (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. Bed rest: Bed rest for 5 days, followed by standard rehabilitation for 2 days. UTMB IRB 17-0064 | 0 | 5 | 0 | 5 | 0 | 5 |
| EG005 | Bed Rest in Healthy Subjects, Physical Therapy (PT)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. Bed rest: Bed rest for 5 days, followed by standard rehabilitation for 2 days Intensive physical therapy: Intensive weight bearing PT, daily, during bed rest. UTMB IRB 17-0064 | 0 | 6 | 0 | 6 | 0 | 6 |
| EG006 | Bed Rest in Type 2 Diabetes (T2DM), Physical Therapy (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. Bed rest: Bed rest for 5 days, followed by standard rehabilitation for 2 days Intensive physical therapy: Intensive weight bearing PT, daily, during bed rest. UTMB IRB 17-0064 | 0 | 6 | 0 | 6 | 1 | 6 |
|
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| D001284 | Atrophy |
| D020763 | Pathological Conditions, Anatomical |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012816 | Signs and Symptoms |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D001519 | Behavior |
| D005791 |
| Patient Care |
| D013812 | Therapeutics |
| D026741 | Physical Therapy Modalities |
| D064797 | Physical Conditioning, Human |
| D015444 | Exercise |
| D009043 | Motor Activity |
| D009068 | Movement |
| D009142 | Musculoskeletal Physiological Phenomena |
| D055687 | Musculoskeletal and Neural Physiological Phenomena |