Preventing the Loss of Muscle and Function in Hospitalized Older Adults
| Status: | Recruiting |
|---|---|
| Conditions: | Neurology |
| Therapuetic Areas: | Neurology |
| Healthy: | No |
| Age Range: | 70 - 85 |
| Updated: | 4/21/2016 |
| Start Date: | January 2015 |
| End Date: | December 2016 |
| Contact: | Micah Drummond, PhD |
| Email: | micah.drummond@hsc.utah.edu |
| Phone: | 801-585-1310 |
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).
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).
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.
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.
Inclusion Criteria:
Age between 70-85 yrs Ability to sign informed consent Montreal cognitive assessment
(MOCA) exam score ≥26 Free-living, prior to admission
Exclusion Criteria:
1. Cardiac abnormalities considered exclusionary by the study physician (e.g., CHF, CAD,
right-to-left shunt)
2. Uncontrolled endocrine or metabolic disease (e.g., hypo/hyperthyroidism, diabetes)
3. GFR <65 mL/min/1.73m2 or evidence of kidney disease or failure
4. Vascular disease or risk factors of peripheral atherosclerosis. (e.g., uncontrolled
hypertension, obesity, diabetes, hypercholesterolemia > 250 mg/dl, claudication or
evidence of venous or arterial insufficiency upon palpitation of femoral, popliteal
and pedal arteries)
5. Risk of DVT including family history of thrombophilia, DVT, pulmonary emboli,
myeloproliferative diseases including polycythemia (Hb>18 g/dL) or thrombocytosis
(platelets>400x103/mL), and connective tissue diseases (positive lupus
anticoagulant), hyperhomocystinemia, deficiencies of factor V Leiden, proteins S and
C, and antithrombine III
6. Use of anticoagulant therapy (e.g., Coumadin, heparin)
7. Elevated systolic pressure >150 or a diastolic blood pressure > 100
8. Implanted electronic devices (e.g., pacemakers, electronic infusion pumps,
stimulators)
9. Cancer or history of successfully treated cancer (less than 1 year) other than basal
cell carcinoma
10. Currently on a weight-loss diet or body mass index > 30 kg/m2
11. Inability to abstain from smoking for duration of study
12. A history of > 20 pack per year smoking
13. HIV or hepatitis B or C*
14. Recent anabolic or corticosteroids use (within 3 months)
15. Subjects with hemoglobin or hematocrit lower than accepted lab values
16. Agitation/aggression disorder (by psychiatric history and exam)
17. History of stroke with motor disability
18. A recent history (<12 months) of GI bleed
19. Depression [>5 on the 15 items Geriatric Depression Scale (GDS)]
20. Alcohol or drug abuse
21. Exercise training (>1 session of moderate to high intensity aerobic or resistance
exercise/week)
22. Liver disease (AST/ALT 2 times above the normal limit, hyperbilirubinemia)
23. Respiratory disease (acute upper respiratory infection, history of chronic lung
disease with resting oxygen saturation <97% on room air)
24. Any other condition or event considered exclusionary by the PI and faculty physician
We found this trial at
1
site
201 Presidents Circle
Salt Lake City, Utah 84108
Salt Lake City, Utah 84108
801) 581-7200
Phone: 801-585-1310
University of Utah Research is a major component in the life of the U benefiting...
Click here to add this to my saved trials
