Muscle Mass During Space Exploration

• Sponsor: The University of Texas Medical Branch, Galveston (Other)
• Overall Status: Completed
• CT.gov ID: NCT00968344
• Collaborator: National Space Biomedical Research Institute (Other)
• Enrollment: 40
• Location: 1
• Arms: 2
• Duration (Months): 68
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Muscle Loss	Dietary Supplement: Leucine; Dietary Supplement: Alanine	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Intervention: leucineIntervention: leucine
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: An Integrated Low-Volume Nutritional Countermeasure to Maintain Muscle Mass and Function During Space Exploration
• Study Start Date: Aug 1, 2009
• Actual Primary Completion Date: Apr 1, 2015
• Actual Study Completion Date: Apr 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Leucine 3-4 g Leucine added to daily meals during bed rest	Dietary Supplement: Leucine; 3-4g Leucine added to daily meals
Placebo Comparator: Placebo 3-4 g Alanine added to daily meals during bed rest	Dietary Supplement: Alanine; Powered amino acid

Outcome Measures

Primary Outcome Measures

1. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 45 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Texas Medical Branch	Galveston	Texas	United States	77555

Sponsors and Collaborators

• The University of Texas Medical Branch, Galveston
• National Space Biomedical Research Institute

Investigators

• Principal Investigator: Douglas Paddon-Jones, PhD, The University of Texas Medical Branch at Galveston

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: The University of Texas Medical Branch, Galveston
• ClinicalTrials.gov Identifier: NCT00968344
• Other Study ID Numbers: 09-121; MA02001
• First Posted: Aug 31, 2009
• Last Update Posted: May 31, 2019
• Last Verified: Dec 1, 2017

Study Results

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.

Arm/Group Title	Leucine	Placebo
Arm/Group Description	3-4 g Leucine added to daily meals during bed rest Leucine: crystalline amino acid	3-4 g Alanine added to daily meals during bed rest Alanine: crystalline amino acid
Period Title: Overall Study
STARTED	20	20
COMPLETED	10	9
NOT COMPLETED	10	11

Baseline Characteristics

Arm/Group Title	Leucine	Placebo	Total
Arm/Group Description	3-4 g Leucine added to daily meals during bed rest Leucine: 3-4g Leucine added to daily meals	3-4 g Alanine added to daily meals during bed rest Alanine: Powered amino acid	Total of all reporting groups
Overall Participants	10	9	19
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	10 100%	9 100%	19 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	4 40%	3 33.3%	7 36.8%
Male	6 60%	6 66.7%	12 63.2%
Region of Enrollment (participants) [Number]
United States	10 100%	9 100%	19 100%

Outcome Measures

1. Primary Outcome

Title	Lean Leg Mass
Description	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

Outcome Measure Data

Analysis Population Description

Healthy community-dwelling men and women aged 45-60 y

Arm/Group Title	Control Group	Leucine (Intervention) Group
Arm/Group Description	Subjects in the control group consumed a 3-4 g of alanine at each meal (an isonitrogenous control)	Subjects in the leucine group consumed 3-4 g of leucine at each meal during bed rest.
Measure Participants	9	10
Mean (Standard Error) [g]	-1.2 (0.2)	-0.9 (0.1)

Adverse Events

Arm/Group Title	Leucine		Placebo
Arm/Group Description	Leucine: 3-4g Leucine added to daily meals		Alanine: Powered amino acid
All Cause Mortality
	Leucine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Leucine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/9 (0%)
Other (Not Including Serious) Adverse Events
	Leucine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/9 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.