Mechanistic Approach to Preventing Atrophy and Restoring Function in Older Adults
Status:
Unknown status
Trial end date:
2020-02-01
Target enrollment:
Participant gender:
Summary
As a function of the growing population of older adults, an estimated 3.48 million total knee
arthroplasty (TKA) procedures will be performed annually in the U.S. by 2030. Despite the
near-universal success of this surgery in mitigating chronic knee pain, TKA is not successful
in restoring long-term physical function in older adults, primarily because of quadriceps
muscle atrophy, which explains 77% of the strength deficits. Overall, strength and functional
mobility in TKA patients is 30-50% below age-matched healthy controls. Functional tasks such
as stair-climbing remain a clinical problem for 75% of patients following TKA. Muscle atrophy
occurs in both operative and non-operative legs, and is essentially permanent for older
patients because of their impaired ability to increase muscle mass. The purpose of this
clinical research is to determine the effects of essential amino acid (EAA) supplementation
on muscle mass, strength, and functional mobility following TKA in older adults. Based on
strong preliminary data, the investigators hypothesize that twice-daily ingestion of 23 g of
EAA for 1 wk before through 6 wk after TKA will increase basal rates of muscle protein
synthesis via inactivation of catabolic signaling, and up-regulation of anabolic and
cyto-protective proteins. The investigators further hypothesize that short-term atrophy
prevention and accelerated return of functional mobility will lead to longer-term structural
and functional adaptations, and improved quality of life in older TKA patients vs. Placebo.
Identifying the mechanisms up-regulated by EAA treatment that preserve muscle volume and
mobility will have a major impact on rehabilitation science. This study will accomplish two
specific aims: (1) determine if EAA elevates basal rates of muscle protein synthesis by
up-regulating anabolic pathways and cyto-protective proteins, and inactivating catabolic
pathways in the short term vs. Placebo and (2) determine if short-term prevention of atrophy,
weakness, and functional mobility leads to positive changes in muscle cell structure and
function, and improved quality of life in the longer term vs. Placebo. This work is
significant because it advances knowledge of the molecular and cellular changes occurring
during muscle atrophy (Placebo) and atrophy prevention (EAA) in a clinical setting using a
treatment that is broadly applicable, is well tolerated, and can be implemented immediately.
Phase:
Phase 2
Details
Lead Sponsor:
University of Oregon
Collaborators:
National Institute on Aging (NIA) Oregon Health and Science University Oregon Research Institute Slocum Center for Orthopedics and Sports Medicine Slocum Research & Education Foundation Slocum Research and Education Foundation University of Arkansas