Mechanistic Approach to Preventing Atrophy and Restoring Function in Older Adults

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.

Conditions

• Muscle Atrophy
• Quality of Life

Interventions

DRUG

Essential Amino Acids (EAA)

Twice daily ingestion of 20 or 23 grams of EAA for 7 days leading up to surgery and continuing for 6 weeks after surgery \[surgery = primary total knee arthroplasty\]

DRUG

Placebo (Alanine)

Twice daily ingestion of 20 or 23 grams Placebo (alanine) for 7 days leading up to surgery and continuing for 6 weeks after surgery \[surgery = primary total knee arthroplasty\]

Sponsors & Collaborators

• Slocum Center for Orthopedics and Sports Medicine

  collaborator OTHER

• Slocum Research & Education Foundation

  collaborator OTHER

• Oregon Research Institute

  collaborator OTHER

• Oregon Health and Science University

  collaborator OTHER

• University of Arkansas

  collaborator OTHER

• National Institute on Aging (NIA)

  collaborator NIH

• University of Oregon

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

50 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2014-12-31

Primary Completion

2020-02-29

Completion

2020-02-29

Countries

• United States

Study Locations