Bed RestEBRNCT01846130
Preserving Muscle Mass and Function in Bedridden Older Adults
A study testing Leucine, Exercise and Whey protein in people with Bed Rest, run by The University of Texas Medical Branch, Galveston at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 60 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Bed Rest
- What is being tested?
- Leucine, Exercise and Whey protein
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 123 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2013to Dec 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age between 60-80
- Ability to sign informed consent
- Ability to pass a mini-mental status exam
- Free-living, prior to admission
Who cannot join
- 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 > 100.
Show all 17Show fewer
- 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/m2.
- A history of > 20 pack per year smoking and/or inability to abstain from smoking for duration of study
- Any subject that is HIV-seropositive or has active hepatitis
- Recent anabolic or corticosteroids use (within 3 months).
- Subjects with hemoglobin or hematocrit lower than accepted lab values.
- Dementia, agitation/aggression disorder
- History of stroke with motor disability
- A recent history (<12 months) of GI bleed
- Any other condition or event considered exclusionary by the PI and faculty physician.
Trial locations and contacts
1 site in 1 country.
United States1 site
Unversity of Texas Medical Branch
Galveston, Texas, 77555
About this study
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.
Read the 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:
- 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.
- 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.
- 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.
- Conditions
- Bed Rest
- Being tested
- Leucine, Exercise, Whey protein
- Keywords
- Bed rest,
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LeucineDietary supplement
ExerciseBehavioural
Whey proteinDietary supplement
| Study group | Role | What they receive |
|---|---|---|
| Control | No intervention | Control bed rest group |
| Leucine | Experimental | Leucine will be administered in mixed meal 3 times a day at 0.06g/kg lean body mass/meal Receives: Dietary Supplement: Leucine |
| Exercise | Experimental | Daily bouts of low intensity, bed-based exercise for 30 min/day @ 70% of stress test determined maximal heart rate. Receives: Behavioral: Exercise |
| Leucine + Exercise | Experimental | Leucine (0.06 g/kg lean body mass/meal, 3 meal/day) and exercise daily bouts of low intensity, bed-based exercise for 30 min/day @ 70% of stress test determined maximal heart rate. Receives: Dietary Supplement: Leucine; Behavioral: Exercise |
| Whey protein | Experimental | 22 g of whey isolate 3x a day (with meals) Receives: Dietary Supplement: Whey protein |
| Whey protein + exercise | Experimental | 22 g whey isolate 3x day (with meals) and daily bouts of low intensity, bed-based exercise for 30 min/day @ 70% of stress test determined maximal heart rate Receives: Behavioral: Exercise; Dietary Supplement: Whey protein |
| Skewed | No intervention | Protein intake is distributed similar to typical American diet with low protein intake at breakfast, intermediate at lunch and high at dinner. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in lean leg mass from baseline following seven days of bed rest and seven days of rehabilitation. (Morphologic primary measure)
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.
Measured: Study day 3, 11, 18, 39
Change in stair climbing power test from baseline following seven days of bed rest and seven days of rehabilitation (Primary functional outcome)
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].
Measured: Study day 3, 11, 18, 39
Change in mixed muscle fractional synthesis rate (FSR) from baseline following seven days of bed rest and seven days of rehabilitation (Primary metabolic outcome)
Mixed muscle FSR will be calculated by measuring the direct incorporation of a stable isotope of phenylalanine into protein using the precursor-product model.
Measured: Study day 4, 11, 18
Secondary outcomes (9)
Change in cell signaling from baseline following seven days of bed rest and seven days of rehabilitation (Secondary metabolic measure)
We will examine protein content and phosphorylation status of key exercise and nutrient sensitive signaling proteins in the mammalian target of rapamycin.
Measured: Study day 4, 11, 18
Change in hormones and cytokines from baseline following seven days of bed rest and seven days of rehabilitation (Secondary Metabolic measure)
Analysis will be performed on existing blood and tissue samples collected for primary metabolic analysis. Serum concentrations of insulin, testosterone, and hsCRP will be analyzed. Serum and muscle tissue concentrations of cytokines and biomarkers, including tumor necrosis factor-alpha (TNF-a), interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, granulocyte-macrophage colony-stimulating factor (GM-CSF), and interferon-gamma (IFN-γ) will also be assessed.
Measured: 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)
Total RNA from skeletal muscle will be isolated and ratios for Atrogin-1/GAPDH, MuRF1/GAPDH and Ubiquitin/GAPDH will be calculated from a portion of the
1st and 3rd muscle biopsy from each study.
Measured: Study day 4, 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)
The activation of NF-κB and actin fragment will be measured pre-and post bed rest and rehabilitation from portions of the 1st and 3rd muscle biopsy taken during each stable isotopic study. Data will also be used to asses muscle protein catabolism.
Measured: 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)
To provide mechanistic insight into gross changes in muscle mass and volume, microscopic assessment of muscle fiber cross sectional area (CSA), fiber type and satellite cell activation will be performed using standard techniques.
Measured: 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)
Surface Electromyography (sEMG) will be collected using a Myomonitor IV wireless EMG system (Delsys, Inc., Boston, MA) to assess neuromuscular factors contributing to force production and fatigue in the vastus lateralis during maximal and submaximal isometric muscle contractions. We will determine degree of neuromuscular activation, fatigue, and rate of EMG activation with measures of root mean square (RMS) EMG, median frequency, and integrated EMG.
Measured: Study day 3, 11, 18, 39
Physical activity monitoring post-bed rest (Secondary functional measure)
Physical activity throughout the study (primarily the post-bed rest/rehabilitation periods) will be used to monitor compliance and obtain a descriptive assessment of prescribed and spontaneous physical activity (StepWatch Activity Monitor; SAM, Cyma Inc., Seattle, WA).
Measured: Study day 11-18
Change in muscle strength and fatigue from baseline following seven days of bed rest and seven days of rehabilitation (secondary functional outcome)
Isokinetic and isometric knee extension torque production are standard, readily comparable tests of muscle function. Tests will be performed on a dynamometer (Biodex, Systems-4, Shirley, NY). The peak of the three maximal attempts will be recorded for strength measures while a 20-repetition protocol will be used to assess fatigue.
Measured: Study day 3, 11, 18, 39
Change in whole body physical function from baseline following seven days of bed rest and seven days of rehabilitation (secondary functional outcome)
Whole body physical function: We previously reported that the Short Physical Performance Battery (SPPB), and five-item physical performance test (5 minute walk, 50 foot walk, 5 step test, functional reach, and floor transfer) lacked the sensitivity to detect changes in older adults following bed rest.
However, given the ease of administration, the clinical relevance of these measures and the fact that this will be only the 2nd bed rest study in older adults, we propose to include these tests a secondary/exploratory measure.
Measured: Study day 3, 11, 18, 39
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2013 (estimated)
- Study startJan 2013
- Primary completionSep 2018
- Study completionDec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bed RestStudies of the same condition, open and under way.
- More trials run by The University of Texas Medical Branch, GalvestonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 123 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Doug Paddon-Jones, Ph.D., Principal investigator, University of Texas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01846130
- Sponsor's protocol ID
- 11-191
- Acronym
- EBR
- Status last verified
- Apr 2018
- First submitted
- 26 Apr 2013
- Last updated
- 24 Jan 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Preserving Muscle Mass and Function in Bedridden Older Adults
- ClinicalTrials.gov ID
- NCT01846130
- Acronym / sponsor ID
- EBR / 11-191
- Conditions
- Bed Rest
- Keywords
- Bed rest,
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 123 participants (actual)
- Lead sponsor
- The University of Texas Medical Branch, GalvestonUniversity, hospital or other
- Study start
- Jan 2013
- Primary completion
- Sep 2018 (actual)
- Study completion
- Dec 2018 (actual)
- First posted
- 3 May 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
- 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.
- 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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Control | No intervention | –Control bed rest group |
| Leucine | Experimental | Dietary Supplement: LeucineLeucine will be administered in mixed meal 3 times a day at 0.06g/kg lean body mass/meal |
| Exercise | Experimental | Behavioral: ExerciseDaily bouts of low intensity, bed-based exercise for 30 min/day @ 70% of stress test determined maximal heart rate. |
| Leucine + Exercise | Experimental | Dietary Supplement: Leucine, Behavioral: ExerciseLeucine (0.06 g/kg lean body mass/meal, 3 meal/day) and exercise daily bouts of low intensity, bed-based exercise for 30 min/day @ 70% of stress test determined maximal heart rate. |
| Whey protein | Experimental | Dietary Supplement: Whey protein22 g of whey isolate 3x a day (with meals) |
| Whey protein + exercise | Experimental | Behavioral: Exercise, Dietary Supplement: Whey protein22 g whey isolate 3x day (with meals) and daily bouts of low intensity, bed-based exercise for 30 min/day @ 70% of stress test determined maximal heart rate |
| Skewed | No intervention | –Protein intake is distributed similar to typical American diet with low protein intake at breakfast, intermediate at lunch and high at dinner. |
Who may qualify
- Ages
- 60 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age between 60-80
- Ability to sign informed consent
- Ability to pass a mini-mental status exam
- Free-living, prior to admission
Key exclusion criteria (17 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Leucine | Dietary supplement | Leucine, Leucine + Exercise |
| Exercise | Behavioural | Exercise, Leucine + Exercise, Whey protein + exercise |
| Whey protein | Dietary supplement | Whey protein, Whey protein + exercise |
Primary outcome
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.
9 secondary outcomes
Change in cell signaling from baseline following seven days of bed rest and seven days of rehabilitation (Secondary metabolic measure)
Time frame: Study day 4, 11, 18
Change in hormones and cytokines from baseline following seven days of bed rest and seven days of rehabilitation (Secondary Metabolic measure)
Time frame: 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)
Time frame: Study day 4, 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)
Time frame: 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)
Time frame: 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)
Time frame: Study day 3, 11, 18, 39
Physical activity monitoring post-bed rest (Secondary functional measure)
Time frame: Study day 11-18
Change in muscle strength and fatigue from baseline following seven days of bed rest and seven days of rehabilitation (secondary functional outcome)
Time frame: Study day 3, 11, 18, 39
Change in whole body physical function from baseline following seven days of bed rest and seven days of rehabilitation (secondary functional outcome)
Time frame: Study day 3, 11, 18, 39
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jan 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Doug Paddon-Jones, Ph.D. principal investigator
University of Texas
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Leucine, Exercise and Whey protein in people with Bed Rest, run by The University of Texas Medical Branch, Galveston at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jan 2019.