Total knee arthroplasty (TKA) is the most common surgical remediation for osteoarthritis (OA), and the number of women undergoing TKA is increasing at a higher rate than for men. Women undergo TKA later in life, resulting in greater functional deficits at the time of surgery, necessitating longer rehabilitation. Despite the success of TKA in eliminating OA-induced knee pain, persistent muscle atrophy following TKA is the greatest clinical barrier to long-term functional recovery and to enhancing quality of life. In 2005, nearly 500,000 TKAs were performed in the US at a cost of over $11 billion. By 2030, it is projected that 3.48 million primary TKAs will be performed annually in the US.
Current Clinical Trial:
Our currently funded 5 year project is a single site clinical trial entitled: Mechanistic approach to preventing atrophy and restoring function in older adults. This project is funded by the National Institute on Aging (R01AG046401) and focuses on reducing muscle atrophy and functional decline after total knee arthroplasty (TKA) using essential amino acid (EAA) supplements. This study is being conducted under an IND (#121601) filed with the FDA and registered at ClinicalTrials.com (NCT02145949). This project is based on our proof-of-principal results recently published in the Journal of Clinical Investigation, link here (Dreyer et al, 2013), and is intended to verify those findings and link changes in muscle volume, functional mobility, diet and activity after TKA with alterations at the cellular level including muscle cross-sectional area, the transcriptome (e.g., Muyskens et al, 2016), cell signaling pathways, inflammation, and markers of satellite cell activation. Additionally, muscle primary (satellite) cells are isolated and will be used in culture to scrutinize how these cells (primary cells and myotubes grown from primary cells) from older TKA patients compare to young healthy primary cells/myotubes under various experimental conditions. Our goal with this approach is to determine which media conditions (hypoxic, inflammatory etc.) that mimic conditions of the muscle tissue post-operatively when the quadriceps is undergoing atrophy affect which pathways and genes. This will allow us to mechanistically interrogate different treatment interventions that prevent atrophy and lower extremity edema that are unwanted consequences of this commonly performed surgery in older adults (please see: Dreyer et al, 2016 and references therein).
Previous Clinical Research Project:
Muscle Regrowth during Physical Rehabilitation and Amino Acid Supplementation. Funded by the Eunice Kennedy Shriver National Institute of Child Health & Human Development / National Center for Medical Rehabilitation Research / NIH
The general hypothesis of this clinical research project is that physical therapy + essential amino acid (EAA) supplementation after total knee replacement (TKR) surgery will restore physical performance and functional independence more than physical therapy alone. Recent studies by our group have demonstrated that EAA ingestion alone can stimulate muscle protein synthesis (anabolic response) in both young and older healthy subjects. Additionally, recent data suggests that EAA ingestion soon after a single bout of exercise increases the anabolic response.
As such, we propose to explore the potential beneficial effects of EAA supplementation alone and in conjunction with physical therapy rehabilitation following TKR surgery. We chose to study older subjects because of the significant quadriceps muscle atrophy and loss of independence that occurs in these individuals following this major surgery. Moreover, older adults loose more muscle mass than younger subjects during bed rest and require more time to recover from surgery. To test our hypothesis we have designed the following study based on evidence that (1) essential amino acid(s) ingestion will be anabolic in older individuals and that (2) ingestion of anabolic nutrients following exercise further promotes muscle protein synthesis than exercise alone. This study is registered with ClinicalTrials.gov.,NCT00760383, where you can find specific details. As well, please feel free to contact us with any questions you may have.
Lab Address: 722 E. 11th Street. Eugene, OR. 97401