Ignite Creation Date:
2024-05-05 @ 7:55 PM
Last Modification Date:
2024-10-26 @ 9:55 AM
Study NCT ID:
NCT00760383
Status:
COMPLETED
Last Update Posted:
2014-12-04
First Post:
2008-09-25
Brief Title:
Muscle Regrowth During Physical Rehabilitation and Amino Acid Supplementation
Sponsor:
University of Oregon
Organization:
University of Oregon
Study Overview
Official Title:
Muscle Regrowth During Physical Rehabilitation and Amino Acid Supplementation
Status:
COMPLETED
Status Verified Date:
2014-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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
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
Detailed Description:
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 eg burn injury primarily resulting from the stress response or decreased protein synthesis eg 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 andor 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
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 eg burn injury primarily resulting from the stress response or decreased protein synthesis eg 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 andor 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 1K01HD057332 | NIH | None | httpsreporternihgovquickSearch1K01HD057332 |