Preserving Muscle Mass and Function in Bedridden Older Adults
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Bed Rest
- Sponsor
- The University of Texas Medical Branch, Galveston
- Enrollment
- 123
- Locations
- 1
- Primary Endpoint
- Change in lean leg mass from baseline following seven days of bed rest and seven days of rehabilitation. (Morphologic primary measure)
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
The investigators propose that low-intensity exercise and supplementing daily meals with leucine or whey will independently and synergistically reduce the deleterious effects of inactivity on skeletal muscle and facilitate recovery during rehabilitation.
Detailed Description
The loss of muscle mass and function in older adults during bed rest is facilitated by defects in the regulation of muscle protein metabolism, including an impaired ability to mount an anabolic response to a mixed nutrient meal. The investigators propose that low-intensity exercise and supplementing daily meals with leucine or whey will independently and synergistically reduce the deleterious effects of inactivity on skeletal muscle and facilitate recovery during rehabilitation. Metabolic measures will include: a) nutrient and exercise-specific markers of translation initiation; b) skeletal muscle protein synthesis; and c) a novel breath test of glucose tolerance. Morphologic and functional measures will include: a) muscle mass and body composition; b) muscle strength and function; and c) motor activation. The investigators will test the following hypotheses in older men and women (65-80 years) during 7 days of bed rest followed by 7 days of inpatient rehabilitation: 1. Inactivity-induced metabolic dysregulation will blunt the anabolic response to meals, facilitating a loss of lean muscle mass, glucose tolerance and functional capacity that is partially restored during rehabilitation. 2. Supplementing daily meals with leucine or whey will maintain nutrient-stimulated translation initiation and preserve the anabolic response to meal ingestion. This will partially preserve lean muscle mass and function during bed rest and facilitate the recovery of functional and metabolic capacity during rehabilitation. 3. Daily low-intensity exercise will preserve motor unit activation, stimulate the exercise-regulated signaling pathway and normalize the anabolic response to meal ingestion. This will partially preserve glucose tolerance, lean muscle mass and function during bed rest and facilitate rehabilitation. This translational project will provide mechanistic and practical insight into strategies to reduce the negative consequences of physical inactivity and promote rehabilitation in aging muscle. Our novel, minimally invasive and clinically interventions have direct application for older hospitalized patients at risk of accelerated muscle loss and diminished functional capacity.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age between 60-80
- •Ability to sign informed consent
- •Ability to pass a mini-mental status exam
- •Free-living, prior to admission
Exclusion Criteria
- •Subjects with cardiac abnormalities considered exclusionary by the study physicians
- •Subjects with uncontrolled metabolic disease
- •A glomerular filtration rate (GRF) \<65 mL/min/1.73m2 or evidence of kidney disease or failure
- •Subjects with 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.
- •Any history of hypo- or hyper-coagulation disorders. (e.g., Coumadin use or history of deep vein thrombosis (DVT) or PE).
- •Subjects with chronically elevated systolic pressure \>170 or a diastolic blood pressure \>
- •Subjects with implanted electronic devices (e.g., pacemakers, electronic infusion pumps, stimulators)
- •Subjects with recently (6 months) treated cancer other than basal cell carcinoma
- •Any subject currently on a weight-loss diet or a body mass index \> 30 kg/m
- •A history of \> 20 pack per year smoking and/or inability to abstain from smoking for duration of study
Outcomes
Primary Outcomes
Change in lean leg mass from baseline following seven days of bed rest and seven days of rehabilitation. (Morphologic primary measure)
Time Frame: Study day 3, 11, 18, 39
The lower body musculature is primarily affected by physical inactivity (19). Lean leg mass will be determined by segmental dual energy x-ray absorptiometry (iDXA:General Electric, Lunar, Madison, WI). The whole body scan will be divided in sub-regions for analysis.
Change in stair climbing power test from baseline following seven days of bed rest and seven days of rehabilitation (Primary functional outcome)
Time Frame: Study day 3, 11, 18, 39
Loss of leg muscle power occurs during prolonged bed rest (-14.4+4 % in 10 days)and is a key factor contributing to impaired mobility, balance and functional capacity. Climbing power will be calculated as the time to ascend 10 steps \[Power = (Distance/Time) x Body Weight\].
Change in mixed muscle fractional synthesis rate (FSR) from baseline following seven days of bed rest and seven days of rehabilitation (Primary metabolic outcome)
Time Frame: Study day 4, 11, 18
Mixed muscle FSR will be calculated by measuring the direct incorporation of a stable isotope of phenylalanine into protein using the precursor-product model.
Secondary Outcomes
- Change in cell signaling from baseline following seven days of bed rest and seven days of rehabilitation (Secondary metabolic measure)(Study day 4, 11, 18)
- Change in protein abundance of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and Actin Fragments from baseline following seven days of bed rest and seven days of rehabilitation. (Secondary metabolic measure)(Study day 3, 18)
- Change in muscle fiber cross sectional area and fiber typing from baseline following seven days of bed rest and seven days of rehabilitation(secondary morphologic measure)(Study day 4, 11, 18)
- Change in motor activation from baseline following seven days of bed rest and seven days of rehabilitation (secondary functional measure)(Study day 3, 11, 18, 39)
- Change in hormones and cytokines from baseline following seven days of bed rest and seven days of rehabilitation (Secondary Metabolic measure)(Study day 3, 11, 18)
- Change in quantitative real-time polymerase chain reaction (PCR) analysis of MAFbx/Atrogin, MuRF1 and Ubiquitin from baseline following seven days of bed rest and seven days of rehabilitation (Secondary metabolic measure)(Study day 4, 18)
- Physical activity monitoring post-bed rest (Secondary functional measure)(Study day 11-18)
- Change in whole body physical function from baseline following seven days of bed rest and seven days of rehabilitation (secondary functional outcome)(Study day 3, 11, 18, 39)
- Change in muscle strength and fatigue from baseline following seven days of bed rest and seven days of rehabilitation (secondary functional outcome)(Study day 3, 11, 18, 39)