Muscular Atrophy Clinical Trial
Official title:
Effect of 14-days of Reduced Physical Activity on Muscle Function and Size, Inflammatory Profile, and Exercise-induced Activation of Stress Responses in Skeletal Muscle in Healthy Older Males
NCT number | NCT02495727 |
Other study ID # | UoB-SRS-01 |
Secondary ID | |
Status | Completed |
Phase | N/A |
First received | |
Last updated | |
Start date | July 2015 |
Est. completion date | October 2017 |
Verified date | May 2018 |
Source | University of Bath |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Muscle size declines at around 0.5-1% per year after 50 years of age, with muscle strength
declining up to twice as fast as muscle size. This may eventually lead to loss of
independence if tasks of daily living become too strenuous to be performed safely. Short
periods of bed rest cause very rapid loss of muscle size and strength, and studies using
healthy older participants have shown that age increases vulnerability to this muscle loss.
However, it is unlikely that healthy individuals would be faced with periods of bed rest
unless suffering a severe illness. In light of this, recent evidence has shown that even just
reducing walking to less than 1,500 steps per day for two weeks caused 4% loss of leg muscle
in over 65 year olds. This amount of activity is roughly the equivalent of being housebound,
something that may become more common into older age, for example due to prolonged bad
weather, or minor injury or illness.
This study will investigate what causes such stark muscle loss during two weeks of reduced
activity, and the impact on skeletal muscle function and size, as well as balance, body
composition, and other indicators of general health such as how the body responds to food or
exercise. Importantly, exercise strategies that could reduce muscle loss during a period of
reduced activity will also be investigated.
In brief, three groups of 10 older men (aged 65-80 years) will undertake two weeks of reduced
physical activity by limiting their daily steps to <1,500/day. All groups will then undertake
a re-training exercise programme to ensure that any losses in muscle strength or size are
regained. One of the groups will be a control, whereby they will undertake the step-reduction
intervention and re-training, but no protective exercise before or during the step-reduction
intervention. This group will allow us to achieve our primary objective of determining the
influence of two weeks of reduced physical activity on muscle strength and size in healthy
older males. The two other groups will undertake either four weeks of strength exercise
training before the step-reduction intervention, or daily home based exercise 'snacking'
during the step-reduction intervention. The potential protective benefits of the exercise
interventions in reducing the impact of two weeks of reduced activity on muscle strength and
size, and any effect on how muscle is re-gained afterwards, will be compared to the 'control'
group.
Status | Completed |
Enrollment | 12 |
Est. completion date | October 2017 |
Est. primary completion date | October 2017 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | Male |
Age group | 65 Years to 80 Years |
Eligibility |
Inclusion Criteria: - Aged 65 to 80 years - Not underweight or obese (body mass index =20 and = 30 kg/m2) - Non-smoker (for >5 years) - Healthy (see exclusion criteria) Exclusion Criteria: - Any chronic illness, cardiac, pulmonary, liver, or kidney abnormalities, uncontrolled hypertension, peripheral arterial disease, insulin- or non-insulin dependent diabetes or other metabolic disorders - all ascertained through medical screening. - Individuals who consume on a daily basis any analgesic or anti-inflammatory drug(s), prescription or non-prescription will be excluded. - Individuals on any medications known to affect protein metabolism (i.e. corticosteroids, non-steroidal anti-inflammatories, or prescription strength acne medications). - Individuals with a history of bone, joint or neuromuscular problems or a current musculoskeletal injury ascertained through medical screening. - Individuals with a known bleeding disorder, on the anticoagulant drug Warfarin, or prone to keloid scarring. - Individuals with a known negative reaction to lidocaine anaesthetic. - Individuals with any joint replacement surgical implants or other artefacts containing metal. - Individuals who complete fewer than 3500 steps per day (as assessed by pedometer prior to the study). - Individuals who score less than 8 on the short physical performance battery. |
Country | Name | City | State |
---|---|---|---|
United Kingdom | University of Bath | Bath | Avon |
Lead Sponsor | Collaborator |
---|---|
University of Bath |
United Kingdom,
Breen L, Stokes KA, Churchward-Venne TA, Moore DR, Baker SK, Smith K, Atherton PJ, Phillips SM. Two weeks of reduced activity decreases leg lean mass and induces "anabolic resistance" of myofibrillar protein synthesis in healthy elderly. J Clin Endocrinol Metab. 2013 Jun;98(6):2604-12. doi: 10.1210/jc.2013-1502. Epub 2013 Apr 15. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Impact of pre-training on all primary and secondary outcomes | Two weeks and four weeks- Change from baseline to post-step-reduction intervention, and from post-step-reduction intervention to post-retraining | ||
Other | Impact of exercise snacking on all primary and secondary outcomes | Two weeks and four weeks- Change from baseline to post-step-reduction intervention, and from post-step-reduction intervention to post-retraining | ||
Primary | Lower limb muscle power | Measured during leg pressing | Two weeks- Change from baseline to post-step-reduction intervention | |
Secondary | Lower limb muscle power | Measured during leg pressing | Two weeks- Change from post-step-reduction intervention to post-re-training intervention | |
Secondary | Lower limb muscle power | For the Pre-training group only: measured during leg pressing | Four weeks- Change from pre-pre-training intervention to 'baseline' pre-step-reduction intervention | |
Secondary | Lower limb muscle force | Measured during leg pressing | Two weeks- Change from baseline to post-step-reduction intervention | |
Secondary | Lower limb muscle force | Measured during leg pressing | Two weeks- Change from post-step-reduction intervention to post-re-training intervention | |
Secondary | Lower limb muscle force | For the Pre-training group only: measured during leg pressing | Four weeks- Change from pre-pre-training intervention to 'baseline' pre-step-reduction intervention | |
Secondary | Lower limb muscle velocity | Measured during leg pressing | Two weeks- Change from baseline to post-step-reduction intervention | |
Secondary | Lower limb muscle velocity | Measured during leg pressing | Two weeks- Change from post-step-reduction intervention to post-re-training intervention | |
Secondary | Lower limb muscle velocity | For the Pre-training group only: measured during leg pressing | Four weeks- Change from pre-pre-training intervention to 'baseline' pre-step-reduction intervention | |
Secondary | Postural sway during standing balance with eyes open and closed | Measured using a force plate | Two weeks- Change from baseline to post-step-reduction intervention | |
Secondary | Postural sway during standing balance with eyes open and closed | Measured using a force plate | Two weeks- Change from post-step-reduction intervention to post-re-training intervention | |
Secondary | Postural sway during standing balance with eyes open and closed | For the Pre-training group only: measured using a force plate | Four weeks- Change from pre-pre-training intervention to 'baseline' pre-step-reduction intervention | |
Secondary | Single leg balance | Measured using the Y-balance test | Two weeks- Change from baseline to post-step-reduction intervention | |
Secondary | Single leg balance | Measured using the Y-balance test | Two weeks- Change from post-step-reduction intervention to post-re-training intervention | |
Secondary | Single leg balance | For the Pre-training group only: measured using the Y-Balance test | Four weeks- Change from pre-pre-training intervention to 'baseline' pre-step-reduction intervention | |
Secondary | Lower limb movement variability | Measured using X-Sens inertial measurement units placed on the lower limb during walking and the Y-balance test | Two weeks- Change from baseline to post-step-reduction intervention | |
Secondary | Lower limb movement variability | Measured using X-Sens inertial measurement units placed on the lower limb during walking and the Y-balance test | Two weeks- Change from post-step-reduction intervention to post-re-training intervention | |
Secondary | Lower limb movement variability | For the Pre-training group only: measured using X-Sens inertial measurement units placed on the lower limb during walking and the Y-balance test | Four weeks- Change from pre-pre-training intervention to 'baseline' pre-step-reduction intervention | |
Secondary | Body composition | Measured using Dual Energy X-ray Absorptiometry | Two weeks- Change from baseline to post-step-reduction intervention | |
Secondary | Body composition | Measured using Dual Energy X-ray Absorptiometry | Two weeks- Change from post-step-reduction intervention to post-re-training intervention | |
Secondary | Body composition | For the Pre-training group only: measured using Dual Energy X-ray Absorptiometry | Four weeks- Change from pre-pre-training intervention to 'baseline' pre-step-reduction intervention | |
Secondary | Lower limb muscle cross-sectional area and tissue density | Measured using peripheral quantitative computed tomography at 66% distal calf length and 25% and 50% distal thigh length | Two weeks- Change from baseline to post-step-reduction intervention | |
Secondary | Lower limb muscle cross-sectional area and tissue density | Measured using peripheral quantitative computed tomography at 66% distal calf length and 25% and 50% distal thigh length | Two weeks- Change from post-step-reduction intervention to post-re-training intervention | |
Secondary | Lower limb muscle cross-sectional area and tissue density | For the Pre-training group only: measured using peripheral quantitative computed tomography at 66% distal calf length and 25% and 50% distal thigh length | Four weeks- Change from pre-pre-training intervention to 'baseline' pre-step-reduction intervention | |
Secondary | Gastrocnemius and quadriceps muscle fibre pennation angle | Measured using ultrasonography at 66% distal length of calf length and 50% distal thigh length | Two weeks- Change from baseline to post-step-reduction intervention | |
Secondary | Gastrocnemius and quadriceps muscle fibre pennation angle | Measured using ultrasonography at 66% distal length of calf length and 50% distal thigh length | Two weeks- Change from post-step-reduction intervention to post-re-training intervention | |
Secondary | Gastrocnemius and quadriceps muscle fibre pennation angle | For the Pre-training group only: measured using ultrasonography at 66% distal length of calf length and 50% distal thigh length | Four weeks- Change from pre-pre-training intervention to 'baseline' pre-step-reduction intervention | |
Secondary | Rates of free-living muscle protein synthesis assessed by stable isotope tracer deuterium oxide (D2O) incorporation rate | Measured by pyrolysis gas chromatography-mass spectrometry | 3, 8, 15, and 18 days- Change in rate of incorporation from baseline to 3 days post-step-reduction intervention | |
Secondary | Free-living adipose triglyceride incorporation assessed by D2O incorporation | Measured by gas chromatography-mass spectrometry | Two weeks- Change from baseline to post-step-reduction intervention | |
Secondary | Total and phosphorylated muscle protein synthesis and breakdown signalling proteins after exercise | Specific signalling proteins to be measured by Western Blotting: Protein kinase B (AKT), mammalian target of rapamycin (mTOR), p70S6 Kinases (p70S6K), 4EBP-1, Muscle RING-finger protein-1 (MuRF-1), muscle atrophy F-box (MAFbx), Forkhead box O (FOXO) | Two weeks- Change from baseline to post-step-reduction intervention | |
Secondary | Messenger Ribonucleic acid (mRMA) expression of muscle protein synthesis and breakdown signalling proteins | Specific signalling proteins to be measured by quantitative polymerase chain reaction: AKT, mTOR, p70S6K, 4EBP-1, MuRF-1, MAFbx, FOXO | Two weeks- Change from baseline to post-step-reduction intervention | |
Secondary | nicotinamide adenine dinucleotide phosphate-oxidase (NAD(P)H oxidase) production in response to strenuous exercise | Measured by colourimetric assay | Two weeks- Change from baseline to post-step-reduction intervention | |
Secondary | Aconitase activity in response to strenuous exercise | Measured by Aconitase assay | Two weeks- Change from baseline to post-step-reduction intervention | |
Secondary | Hydrogen peroxide production in response to strenuous exercise | Measured by Amplex Red assay | Two weeks- Change from baseline to post-step-reduction intervention | |
Secondary | Heat Shock Protein 27 muscle content in response to strenuous exercise | Measured by enzyme linked immunosorbent assay | Two weeks- Change from baseline to post-step-reduction intervention | |
Secondary | Inflammation and oxidative stress response transcription factor activation in response to strenuous exercise | Measured by enzyme linked immunosorbent assay | Two weeks- Change from baseline to post-step-reduction intervention | |
Secondary | Subcutaneous adipose tissue cytokine secretion at rest | Specifically leptin, adiponectin, Interleukin (IL)-6, Tumour necrosis factor alpha (TNFa), IL-8, and IL-1ra will be measured using enzyme linked immunosorbent assay | Two weeks- Change from baseline to post-step-reduction intervention | |
Secondary | Systemic cytokines at rest | Specifically IL-6, TNFa, and C-reactive protein (CRP) will be measured using enzyme linked immunosorbent assay (ELISA) | Two weeks- Change from baseline to post-step-reduction intervention | |
Secondary | Cytotoxic "killer" T lymphocyte interferon-gamma production in response to proteins from common viruses | Measured by Enzyme-Linked ImmunoSpot (ELIspot) assay, specifically response to proteins from Epstein Barr Virus, Cytomegalovirus, Herpes Simplex Virus 1 and 2, Adenovirus, Varicella Zoster Virus and Influenza Virus will be measure | Two weeks- Change from baseline to post-step-reduction intervention | |
Secondary | Postprandial blood insulin concentration | Measured by mixed meal tolerance test of 2 g/kg body mass (BM) carbohydrate; 0.8 g/kg BM fat; 0.4 g/kg BM protein | Two weeks- Change from baseline to post-step-reduction intervention | |
Secondary | Postprandial blood glucose concentration | Measured by mixed meal tolerance test of 2 g/kg body mass (BM) carbohydrate; 0.8 g/kg BM fat; 0.4 g/kg BM protein | Two weeks- Change from baseline to post-step-reduction intervention | |
Secondary | Postprandial blood triglyceride concentration | Measured by mixed meal tolerance test of 2 g/kg body mass (BM) carbohydrate; 0.8 g/kg BM fat; 0.4 g/kg BM protein | Two weeks- Change from baseline to post-step-reduction intervention | |
Secondary | Postprandial blood high-density lipoprotein concentration | Measured by mixed meal tolerance test of 2 g/kg body mass (BM) carbohydrate; 0.8 g/kg BM fat; 0.4 g/kg BM protein | Two weeks- Change from baseline to post-step-reduction intervention | |
Secondary | Postprandial blood low-density lipoprotein concentration | Measured by mixed meal tolerance test of 2 g/kg body mass (BM) carbohydrate; 0.8 g/kg BM fat; 0.4 g/kg BM protein | Two weeks- Change from baseline to post-step-reduction intervention | |
Secondary | Postprandial blood non-esterified fatty acid concentration | Measured by mixed meal tolerance test of 2 g/kg body mass (BM) carbohydrate; 0.8 g/kg BM fat; 0.4 g/kg BM protein | Two weeks- Change from baseline to post-step-reduction intervention | |
Secondary | Dietary intake | Measured with 3-day food diary record sheets to obtain total daily calories consumed and macronutrient profile | Approximately 4 or 8 weeks- Change from preliminary screening period to during step-reduction intervention | |
Secondary | Sleep quality | Measured with the Pittsburgh Sleep Quality Index questionnaire | Two weeks- Change from baseline to post-step-reduction intervention | |
Secondary | Quality of life | Measured with the WHOQOL-BREF questionnaire | Two weeks- Change from baseline to post-step-reduction intervention | |
Secondary | Qualitative feedback of participant experience of the interventions | Measured with phone or face to face qualitative interview | Less than 6 weeks post-re-training intervention |
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