Muscle Regrowth During Physical Rehabilitation and Amino Acid Supplementation
1 other identifier
interventional
60
1 country
2
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for not_applicable
Started Jun 2008
Longer than P75 for not_applicable
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
June 1, 2008
CompletedFirst Submitted
Initial submission to the registry
September 25, 2008
CompletedFirst Posted
Study publicly available on registry
September 26, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2013
CompletedResults Posted
Study results publicly available
December 4, 2014
CompletedDecember 4, 2014
December 1, 2014
5.5 years
September 25, 2008
April 17, 2014
December 1, 2014
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Stair Time up
6 weeks
Quadriceps Muscle Strength
6 weeks
Secondary Outcomes (1)
Mid-thigh Muscle Volume
6 weeks
Study Arms (2)
EAA+PT
EXPERIMENTAL20 g EAA daily for 7 days prior to TKA surgery and for 14 days after surgery.
ALA+PT
PLACEBO COMPARATOR20 g NEAA daily for 7 days prior to TKA surgery and for 14 days after surgery.
Interventions
Subjects will ingest 20 grams of essential amino acids (EAA) daily for 7 days prior to total knee arthroplasty (TKA) surgery and for 14 days after surgery daily. On the days they are seen by physical therapy (PT) they will ingest the EAA supplement 30 minutes after the end of each PT rehabilitation session.
Subjects will ingest 20 grams of non-essential amino acid (NEAA) daily for 7 days prior to total knee arthroplasty (TKA) surgery and for 14 days after surgery daily. On the days they are seen by physical therapy (PT) they will ingest the NEAA supplement 30 minutes after the end of each PT rehabilitation session.
Eligibility Criteria
You may qualify if:
- Total Knee Arthroplasty surgical candidate
You may not qualify if:
- Overt muscle disease
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
University of Oregon
Eugene, Oregon, 97401-1240, United States
Slocum Center for Orthopedics and Sports Medicine
Eugene, Oregon, 97401, United States
Related Publications (9)
Dreyer HC, Drummond MJ, Pennings B, Fujita S, Glynn EL, Chinkes DL, Dhanani S, Volpi E, Rasmussen BB. Leucine-enriched essential amino acid and carbohydrate ingestion following resistance exercise enhances mTOR signaling and protein synthesis in human muscle. Am J Physiol Endocrinol Metab. 2008 Feb;294(2):E392-400. doi: 10.1152/ajpendo.00582.2007. Epub 2007 Dec 4.
PMID: 18056791BACKGROUNDFujita S, Dreyer HC, Drummond MJ, Glynn EL, Cadenas JG, Yoshizawa F, Volpi E, Rasmussen BB. Nutrient signalling in the regulation of human muscle protein synthesis. J Physiol. 2007 Jul 15;582(Pt 2):813-23. doi: 10.1113/jphysiol.2007.134593. Epub 2007 May 3.
PMID: 17478528BACKGROUNDDreyer HC, Fujita S, Cadenas JG, Chinkes DL, Volpi E, Rasmussen BB. Resistance exercise increases AMPK activity and reduces 4E-BP1 phosphorylation and protein synthesis in human skeletal muscle. J Physiol. 2006 Oct 15;576(Pt 2):613-24. doi: 10.1113/jphysiol.2006.113175. Epub 2006 Jul 27.
PMID: 16873412BACKGROUNDFujita S, Dreyer HC, Drummond MJ, Glynn EL, Volpi E, Rasmussen BB. Essential amino acid and carbohydrate ingestion before resistance exercise does not enhance postexercise muscle protein synthesis. J Appl Physiol (1985). 2009 May;106(5):1730-9. doi: 10.1152/japplphysiol.90395.2008. Epub 2008 Jun 5.
PMID: 18535123BACKGROUNDDrummond MJ, Dreyer HC, Pennings B, Fry CS, Dhanani S, Dillon EL, Sheffield-Moore M, Volpi E, Rasmussen BB. Skeletal muscle protein anabolic response to resistance exercise and essential amino acids is delayed with aging. J Appl Physiol (1985). 2008 May;104(5):1452-61. doi: 10.1152/japplphysiol.00021.2008. Epub 2008 Mar 6.
PMID: 18323467BACKGROUNDDreyer HC, Blanco CE, Sattler FR, Schroeder ET, Wiswell RA. Satellite cell numbers in young and older men 24 hours after eccentric exercise. Muscle Nerve. 2006 Feb;33(2):242-53. doi: 10.1002/mus.20461.
PMID: 16315322BACKGROUNDDreyer HC, Volpi E. Role of protein and amino acids in the pathophysiology and treatment of sarcopenia. J Am Coll Nutr. 2005 Apr;24(2):140S-145S. doi: 10.1080/07315724.2005.10719455.
PMID: 15798081BACKGROUNDRatchford SM, Bailey AN, Senesac HA, Hocker AD, Smolkowski K, Lantz BA, Jewett BA, Gilbert JS, Dreyer HC. Proteins regulating cap-dependent translation are downregulated during total knee arthroplasty. Am J Physiol Regul Integr Comp Physiol. 2012 Mar 15;302(6):R702-11. doi: 10.1152/ajpregu.00601.2011. Epub 2011 Dec 28.
PMID: 22204954RESULTDreyer HC, Strycker LA, Senesac HA, Hocker AD, Smolkowski K, Shah SN, Jewett BA. Essential amino acid supplementation in patients following total knee arthroplasty. J Clin Invest. 2013 Nov;123(11):4654-66. doi: 10.1172/JCI70160. Epub 2013 Oct 25.
PMID: 24135139DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Hans C. Dreyer, PT, PhD
- Organization
- Human Physiology, University of Oregon
Study Officials
- PRINCIPAL INVESTIGATOR
Hans C Dreyer, PT, PhD
Assistant Professor, Department of Human Physiology
Publication Agreements
- PI is Sponsor Employee
- Yes
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- University of Oregon
Study Record Dates
First Submitted
September 25, 2008
First Posted
September 26, 2008
Study Start
June 1, 2008
Primary Completion
December 1, 2013
Study Completion
December 1, 2013
Last Updated
December 4, 2014
Results First Posted
December 4, 2014
Record last verified: 2014-12