Preventing the Loss of Muscle and Function in Hospitalized Older Adults
Condition: Muscular Atrophy
MeSH terms: Muscular Atrophy
Study type: Interventional

Summary: 
      One third of independent older adults over the age of 65y will be hospitalized for an acute
      medical illness, injury, or operative procedure. Unfortunately, 50% of these older adults
      will experience functional decline during their hospital stay from the amount of time they
      are physically inactive and in bed. Following discharge, the functional deficits can persist
      for months and in many instances never return to pre-hospitalization levels thus compounding
      morbidity, health care costs and dying. A classic consequence of short-term bed rest in older
      adults is the significant loss in skeletal muscle mass which underlies the accelerated leg
      strength deficits. The investigator has shown that an important mechanism of skeletal muscle
      loss is the inability of nutrients to stimulate a normal muscle protein synthesis response; a
      process highly regulated by the mammalian target of rapamycin signaling pathway (mTOR) and
      amino acid transporters. Day to day maintenance of force generating muscle tissue is dictated
      by anabolic stimulation from muscle contraction and essential amino acid ingestion.
      Therefore, anabolic interventions such as neuromuscular electrical stimulation (NMES) and
      high quality protein supplementation that contains a high proportion of essential amino acids
      (whey protein) may be promising approach to maintain leg muscle mass and strength in
      hospitalized older adults and prevent the long term consequences of repeated periods of
      short-term physical inactivity. The purpose of this study is to test in older adults if the
      combination of NMES and protein supplementation is capable of preserving muscle mass and
      strength and maintaining muscle nutrient anabolic sensitivity during bed rest. The
      investigators current hypotheses are that daily NMES and protein supplementation during
      5-days of bed rest in older adults will: 1) preserve lower extremity muscle mass and strength
      and 2) maintain muscle nutrient anabolic sensitivity as measured by mTOR signaling and amino
      acid transporter expression. The long term goal is to utilize this inpatient preventative
      therapeutic approach in a clinical setting in which muscle mass and strength deficits are
      profound (e.g., intensive care patients).
    

Detailed description: 
      A majority of older adults experience repeated periods of physical inactivity during acute
      illnesses, injuries or after an operative procedure. Following discharge from the hospital,
      daily activities are adversely impacted. Infirmity follows repeated periods of inactivity
      (termed "catabolic hits") that can occur over an older adults' lifespan and lead to a
      downward spiral of potentially irrecoverable deficits in physical function resulting in
      increased health care costs, loss of independence, and premature death. The hallmark sign of
      short-term physical inactivity in older adults is the rapid deterioration of skeletal muscle
      mass and strength. Understandably, little attention is placed on physical function during
      these requisite periods of inactivity as the medical management and/or postoperative
      recuperation is the focus. However, the muscle deficits that follow as a result of acute
      hospitalization can have profound long-term consequences.

      Muscle contraction and essential amino acids are powerful independent anabolic stimuli and
      fundamental to maintain skeletal muscle mass and strength. The primary mechanism of disuse
      atrophy during short-term bed rest in older adults is the reduced acute nutrient stimulation
      of muscle protein synthesis regulated by the mammalian target of rapamycin (mTOR) signaling
      pathway and amino acid transporter expression (i.e., LAT1). Intervening with essential amino
      acid supplements can maintain some muscle function in older adults during bed rest, but it
      does not preserve muscle mass. Neuromuscular electrical stimulation (NMES) as a muscle
      intervention is also feasible, but alone is not a panacea. NMES has recently been shown to
      acutely stimulate protein synthesis in ambulatory older adults with diabetes and attenuate
      some loss in muscle mass in critically ill patients. The investigator suggests that,
      together, daily NMES, and a high quality protein source of EAAs (PRO), can be a potent
      two-pronged approach to preserve the loss of muscle and strength in older adults confined to
      short-term bed rest. The goal is to test if the combination of NMES and PRO will maintain
      muscle mass, strength, nutrient-induced mTOR signaling and amino acid transporter expression
      in older adults during bed rest. The central hypothesis for this project which will support
      this next step is that a daily combination of NMES and PRO in older adults experiencing bed
      rest will preserve: 1) leg muscle mass and knee extensor strength and 2) muscle anabolic
      sensitivity in response to acute nutrient ingestion, as measured by mTOR signaling and LAT1
      expression.
    

Intervention name(s): NMES; Protein; non-protein placebo supplement
Intervention type(s): Device; Dietary Supplement; Dietary Supplement
Intervention description(s): device is used to stimulate muscle contraction in the legs of the patient. The intervention will be used 3 times a day during bed rest.; supplement will used to enhance muscle anabolism. The intervention will be provided 3 times a day during bed rest.; supplement will be used as a placebo to control participants. The supplement will be provided 3x a day during bed rest.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention