Muscle Regrowth During Physical Rehabilitation and Amino Acid Supplementation
| Status: | Completed |
|---|---|
| Conditions: | Arthritis, Osteoarthritis (OA) |
| Therapuetic Areas: | Rheumatology |
| Healthy: | No |
| Age Range: | 60 - 80 |
| Updated: | 2/7/2015 |
| Start Date: | June 2008 |
| End Date: | August 2013 |
| Contact: | Crystal Mills |
| Email: | crystal.mills@slocumcenter.com |
| Phone: | 541-868-3232 |
The general hypothesis is that in older adults muscle regrowth after an acute
musculoskeletal stress will be positively influenced by traditional physical rehabilitation,
and further enhanced by nutritional supplementation. Using state-of-the-art stable isotope
methodologies for the study of muscle metabolism and methodologies for the measurement of
cell signaling, we will test the following specific hypotheses: 1) Total knee arthroplasty
(TKA) induces an acute net protein catabolism mainly by reducing muscle protein synthesis;
2) TKA induced catabolism is attenuated by the ingestion of essential amino acids (EAA); 3)
EAA supplementation in combination with physical therapy (PT) will stimulate muscle protein
synthesis and mTOR signaling to a greater extent than PT with Placebo; and 4) EAA
supplementation during TKA PT rehabilitation will improve muscle strength, muscle volume and
functional outcomes to a greater extent than PT with Placebo.
Public Benefit: This research will focus rehabilitation efforts on specific and currently
unresolved mechanisms responsible for muscle loss following total knee replacement in older
adults. While knee pain due to bone arthritis is often alleviated after knee replacement,
complete return of physical function and independence is difficult to achieve. This research
will help to restore physical function and independence in the rapidly growing population of
older adults with knee arthritis.
musculoskeletal stress will be positively influenced by traditional physical rehabilitation,
and further enhanced by nutritional supplementation. Using state-of-the-art stable isotope
methodologies for the study of muscle metabolism and methodologies for the measurement of
cell signaling, we will test the following specific hypotheses: 1) Total knee arthroplasty
(TKA) induces an acute net protein catabolism mainly by reducing muscle protein synthesis;
2) TKA induced catabolism is attenuated by the ingestion of essential amino acids (EAA); 3)
EAA supplementation in combination with physical therapy (PT) will stimulate muscle protein
synthesis and mTOR signaling to a greater extent than PT with Placebo; and 4) EAA
supplementation during TKA PT rehabilitation will improve muscle strength, muscle volume and
functional outcomes to a greater extent than PT with Placebo.
Public Benefit: This research will focus rehabilitation efforts on specific and currently
unresolved mechanisms responsible for muscle loss following total knee replacement in older
adults. While knee pain due to bone arthritis is often alleviated after knee replacement,
complete return of physical function and independence is difficult to achieve. This research
will help to restore physical function and independence in the rapidly growing population of
older adults with knee arthritis.
The goal of this translational research project is to identify key mechanisms involved in
regulating skeletal muscle loss and regrowth following total knee arthroplasty (TKA). Total
knee arthroplasty induces significant declines in muscle mass and strength, which is
directly responsible for reduced function, specifically functional independence. Such
declines in muscle strength and volume and activities of daily living (getting up from a
chair, climbing stairs and walking) can persist for up to 2 years.
Atrophy is the direct result of an imbalance between muscle protein synthesis and breakdown.
However, there are two quite distinct mechanisms leading to muscle loss: accelerated protein
breakdown (e.g. burn injury), primarily resulting from the stress response, or decreased
protein synthesis (e.g., immobilization). In case of severe stress, muscle protein synthesis
actually increases, although not adequately to impede muscle loss, and anabolic stimuli,
such as nutrition, cannot counteract muscle atrophy. On the other hand, decreased protein
synthesis from inactivity can be stimulated by nutrition and exercise, thereby reducing or
preventing atrophy. Currently, we do not know which condition predominates following TKA:
surgical stress-induced catabolism or immobility-associated declines in synthesis . What is
not known is which signaling pathway predominates following TKA; stress induced catabolism
or immobility associated declines in synthesis. Our goal is to determine which model (stress
or inactivity) accounts for the acute and rapid muscle loss following TKA in order to better
focus rehabilitation efforts.
Our general hypothesis is that quadriceps atrophy following TKA surgery is primarily due to
inactivity, which can be counteracted by physical therapy (PT) and essential amino acid
(EAA) supplementation. Our goal is to delineate the basic mechanisms underlying muscle loss
with TKA, and based on this new information, to find novel rehabilitation strategies to
accelerate recovery of normal function from TKA.
Thus, our plan is to test in older adults the following specific hypothesis:
1. TKA induces an acute and severe net protein catabolism by reducing muscle protein
synthesis
2. TKA induced catabolism is attenuated with the ingestion of EAA
3. EAA supplementation following PT will stimulate muscle protein synthesis and mTOR
signaling to a greater extent than PT with Placebo
4. EAA supplementation during TKA PT rehabilitation will improve muscle strength, muscle
volume and functional outcomes to a greater extent than PT with Placebo
To test our specific hypothesis we will address the following specific aims:
1. To determine if TKA surgery reduces muscle protein synthesis and/or increases muscle
protein breakdown
2. To determine if muscle protein synthesis is acutely increased with the ingestion of EAA
following TKA surgery
3. To determine if muscle protein synthesis and mTOR signaling will be stimulated by PT
rehabilitation and enhanced by EAA supplementation
4. To determine if EAA supplementation during TKA with traditional PT for 6 weeks improves
muscle strength, muscle volume and functional outcomes This application will provide
preliminary data for the submission of an R01 grant to further determine the mechanisms
leading to successful return of quadriceps muscle strength and function following TKA.
Essential amino acids are inexpensive, well tolerated and easily digestible and have
been shown to independently stimulate muscle protein synthesis and components of the
anabolic mTOR signaling pathway. My goal of increasing muscle strength and functional
mobility is specifically outlined in the National Center for Medical Rehabilitation
Research Seven Priority Areas and are in line with the NIH roadmap and priorities, and
will help us to understand muscle protein metabolism during physical therapy
rehabilitation. By adopting a mechanism-driven, translational research design that
links changes in cell signaling with functional outcome measures (cell → system →
function) we will capture key physiological events responsible for the regulation of
muscle mass and function following TKA.
regulating skeletal muscle loss and regrowth following total knee arthroplasty (TKA). Total
knee arthroplasty induces significant declines in muscle mass and strength, which is
directly responsible for reduced function, specifically functional independence. Such
declines in muscle strength and volume and activities of daily living (getting up from a
chair, climbing stairs and walking) can persist for up to 2 years.
Atrophy is the direct result of an imbalance between muscle protein synthesis and breakdown.
However, there are two quite distinct mechanisms leading to muscle loss: accelerated protein
breakdown (e.g. burn injury), primarily resulting from the stress response, or decreased
protein synthesis (e.g., immobilization). In case of severe stress, muscle protein synthesis
actually increases, although not adequately to impede muscle loss, and anabolic stimuli,
such as nutrition, cannot counteract muscle atrophy. On the other hand, decreased protein
synthesis from inactivity can be stimulated by nutrition and exercise, thereby reducing or
preventing atrophy. Currently, we do not know which condition predominates following TKA:
surgical stress-induced catabolism or immobility-associated declines in synthesis . What is
not known is which signaling pathway predominates following TKA; stress induced catabolism
or immobility associated declines in synthesis. Our goal is to determine which model (stress
or inactivity) accounts for the acute and rapid muscle loss following TKA in order to better
focus rehabilitation efforts.
Our general hypothesis is that quadriceps atrophy following TKA surgery is primarily due to
inactivity, which can be counteracted by physical therapy (PT) and essential amino acid
(EAA) supplementation. Our goal is to delineate the basic mechanisms underlying muscle loss
with TKA, and based on this new information, to find novel rehabilitation strategies to
accelerate recovery of normal function from TKA.
Thus, our plan is to test in older adults the following specific hypothesis:
1. TKA induces an acute and severe net protein catabolism by reducing muscle protein
synthesis
2. TKA induced catabolism is attenuated with the ingestion of EAA
3. EAA supplementation following PT will stimulate muscle protein synthesis and mTOR
signaling to a greater extent than PT with Placebo
4. EAA supplementation during TKA PT rehabilitation will improve muscle strength, muscle
volume and functional outcomes to a greater extent than PT with Placebo
To test our specific hypothesis we will address the following specific aims:
1. To determine if TKA surgery reduces muscle protein synthesis and/or increases muscle
protein breakdown
2. To determine if muscle protein synthesis is acutely increased with the ingestion of EAA
following TKA surgery
3. To determine if muscle protein synthesis and mTOR signaling will be stimulated by PT
rehabilitation and enhanced by EAA supplementation
4. To determine if EAA supplementation during TKA with traditional PT for 6 weeks improves
muscle strength, muscle volume and functional outcomes This application will provide
preliminary data for the submission of an R01 grant to further determine the mechanisms
leading to successful return of quadriceps muscle strength and function following TKA.
Essential amino acids are inexpensive, well tolerated and easily digestible and have
been shown to independently stimulate muscle protein synthesis and components of the
anabolic mTOR signaling pathway. My goal of increasing muscle strength and functional
mobility is specifically outlined in the National Center for Medical Rehabilitation
Research Seven Priority Areas and are in line with the NIH roadmap and priorities, and
will help us to understand muscle protein metabolism during physical therapy
rehabilitation. By adopting a mechanism-driven, translational research design that
links changes in cell signaling with functional outcome measures (cell → system →
function) we will capture key physiological events responsible for the regulation of
muscle mass and function following TKA.
Inclusion Criteria:
- Total Knee Arthroplasty surgical candidate
Exclusion Criteria:
- Overt muscle disease
We found this trial at
2
sites
Click here to add this to my saved trials
Click here to add this to my saved trials