Clinical trial NCT00968344: Muscle Mass During Space Exploration
Official title: An Integrated Low-Volume Nutritional Countermeasure to Maintain Muscle Mass and Function During Space Exploration
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Muscle Loss
Lead sponsor: The University of Texas Medical Branch, Galveston
Sponsor class: OTHER
Collaborators: name: National Space Biomedical Research Institute
First posted: 2009-08-31
Enrollment: 40
Sex: ALL
Minimum age (years): 45
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Intervention: leucine
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Lean Leg Mass
timeFrame: At baseline prior to beginning bed rest and after 14 days of bed rest
Secondary outcomes:
Other outcomes:
Locations:
city: Galveston
country: United States
facility: The University of Texas Medical Branch
state: Texas
Study officials:
affiliation: The University of Texas Medical Branch at Galveston
name: Douglas Paddon-Jones, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: English KL, Mettler JA, Ellison JB, Mamerow MM, Arentson-Lantz E, Pattarini JM, Ploutz-Snyder R, Sheffield-Moore M, Paddon-Jones D. Leucine partially protects muscle mass and function during bed rest in middle-aged adults. Am J Clin Nutr. 2016 Feb;103(2):465-73. doi: 10.3945/ajcn.115.112359. Epub 2015 Dec 30.