Muscle Loss
Conditions
Brief summary
The investigators will test the following hypotheses: 1. Bedrest will blunt the anabolic response to a mixed nutrient meal, facilitating a loss of muscle mass and functional capacity that is only partially restored during rehabilitation. 2. Enriching daily meals with leucine will promote protein synthesis and maintain the anabolic response to mixed nutrient meal ingestion. This will preserve lean muscle mass and function during bedrest and facilitate the recovery of functional and metabolic capacity during rehabilitation.
Detailed description
Our long-term goal is to identify, prevent and remedy defects in the metabolic pathway that contribute to the loss of muscle mass and function during exposure to microgravity. Demographic data indicate that the average age of shuttle crew members has increased from 40.7 yrs in 1995 to 46.7 yrs in 2007 with an increasing number of astronauts over 50 yrs of age. We contend that the loss of muscle mass and function during spaceflight is facilitated by an age-associated, progressive impairment in the ability to mount an anabolic response to standard mixed nutrient meals. We propose that enriching daily meals with a low-volume leucine supplement will reduce the deleterious effects of microgravity on skeletal muscle and facilitate recovery during rehabilitation. We will employ our established 14 day bed rest protocol to model the skeletal muscle unloading that occurs during microgravity. We will also examine recovery of muscle mass and functional capacity during a 7 day rehabilitation period. We will study 2 groups: CON (Bedrest/Recovery + Placebo; n=15), LEU (Bedrest/Recovery + Leucine; n=15). We will assess a) markers of translation initiation, b) muscle protein synthesis, c) muscle mass and body composition and d) strength and aerobic capacity.
Interventions
DIETARY_SUPPLEMENTLeucine
3-4g Leucine added to daily meals
DIETARY_SUPPLEMENTAlanine
Powered amino acid
Sponsors
National Space Biomedical Research Institute
The University of Texas Medical Branch, Galveston
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Intervention: leucine
Eligibility
Sex/Gender
ALL
Age
45 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
1. Age between 45-60 2. Ability to sign informed consent
Exclusion criteria
1. Subjects with cardiac abnormalities considered exclusionary by the study physicians 2. Subjects with uncontrolled metabolic disease 3. A GFR \<65 mL/min/1.73m2 or evidence of kidney disease or failure 4. Subjects with vascular disease or risk factors of peripheral atherosclerosis 5. Any history of hypo- or hyper-coagulation disorders. (e.g., Coumadin use or history of DVT or PE) 6. Subjects with chronically elevated systolic pressure \>150 or a diastolic blood pressure \> 100 7. Subjects with implanted electronic devices (e.g., pacemakers, electronic infusion pumps, stimulators) 8. Subjects with recently (6 months) treated cancer other than basal cell carcinoma 9. Any subject currently on a weight-loss diet or a body mass index \> 30 kg/m2 10. Inability to abstain from smoking for duration of study 11. A history of \> 20 pack per year smoking 12. Any subject that is HIV-seropositive or has active hepatitis 13. Recent anabolic or corticosteroids use (within 3 months) 14. Subjects with hemoglobin or hematocrit lower than accepted lab values 15. Agitation/aggression disorder 16. History of stroke with motor disability 17. A recent history (\<12 months) of GI bleed 18. Any other condition or event considered exclusionary by the PI and faculty physician
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Lean Leg Mass | At baseline prior to beginning bed rest and after 14 days of bed rest | DEXA scan of both legs pre/post bed rest |
Countries
United States
Participant flow
Recruitment details
2009-2014: we recruited and studied middle-aged men and women (45-60 years), representative of the ethnic makeup of the United States. Volunteers were recreationally active but athletically untrained.After providing written informed consent, volunteers were screened in the UTMB Institute for Translational Sciences-Clinical Research Center.
Participants by arm
| Arm | Count |
|---|---|
| Leucine 3-4 g Leucine added to daily meals during bed rest
Leucine: 3-4g Leucine added to daily meals | 10 |
| Placebo 3-4 g Alanine added to daily meals during bed rest
Alanine: Powered amino acid | 9 |
| Total | 19 |
Baseline characteristics
| Characteristic | Leucine | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 9 Participants | 19 Participants |
| Region of Enrollment United States | 10 participants | 9 participants | 19 participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 10 | 0 / 9 |
| serious Total, serious adverse events | 0 / 10 | 0 / 9 |
Outcome results
Primary
Lean Leg Mass
DEXA scan of both legs pre/post bed rest
Time frame: At baseline prior to beginning bed rest and after 14 days of bed rest
Population: Healthy community-dwelling men and women aged 45-60 y
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Group | Lean Leg Mass | -1.2 g | Standard Error 0.2 |
| Leucine (Intervention) Group | Lean Leg Mass | -0.9 g | Standard Error 0.1 |