Two Weeks of Reduced Activity and Skeletal Muscle Health in Older Men
Condition: Muscular Atrophy
MeSH terms: Muscular Atrophy; Atrophy
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      Overall study design:

      This study will be structured as a randomised control trial with two exercise treatment
      groups and one 'control' group. All three groups will undergo 14-days of reduced activity by
      restricting daily walking to less than 1,500 steps. One group will undertake four weeks of
      resistance exercise pre-training immediately prior to the 14-day step-reduction (PT group),
      and another group will undertake short bouts of home-based exercise (exercise snacking) every
      day during the 14-day step-reduction (ES group). The control group will undertake the 14-day
      step-reduction with neither exercise strategy. All three groups will then undertake two weeks
      of laboratory based resistance exercise training immediately after the step-reduction period,
      and will be offered a further six weeks of gym based personal training, and a six month gym
      and swimming pool membership at the Team Bath Sports Training Village.

      Following advertisement of the study, interested potential participants will be asked to
      contact the chief investigator for further information via telephone or email correspondence.
      Further details including inclusion criteria will be provided verbally, and a full
      participant information sheet will be sent to potential participants that feel that they meet
      the inclusion criteria. If the potential participant chooses to be considered for inclusion
      in the trial, they must sign the consent form for initial screening and will be invited to a
      medical screening meeting with a member of the research team.

      Preliminary assessment:

      All potential participants will undergo screening to assess eligibility for inclusion before
      proceeding. This will include an objective assessment of physical function (Short Physical
      Performance Battery) in which simple tests of walking speed, ability to repeatedly rise from
      a chair, and simple standing balance are scored based on set criteria. Only participants
      scoring over 7 out of 12 will be eligible to participate. Participants will wear a
      step-counter (pedometer), and a physical activity monitor (BodyMedia armband) for one week,
      and be asked to record all food and drink consumed for three days (including one weekend day)
      using a provided diet record sheet. Only individuals who average 3,500 steps per day or above
      will be included in the study. At the end of this monitoring period, eligible participants
      will be asked to sign a consent form for the main study, and will be randomly assigned to an
      experimental group by minimisation.

      Familiarisation with strength, power, and balance assessment:

      Eligible participants will be invited to the laboratory for two familiarisation sessions with
      the muscle strength, balance, and neural drive testing tools. Participants will be asked to
      wear light clothes in which it is comfortable to perform exercise. These familiarisation
      sessions will be at least five but less 14 days apart, with the second session at least five
      days before the start of the pre-training for the PT group, and at least five but less than
      14 days before the pre-step-reduction main trial.

      Pre-training group:

      Participants in the PT group will be asked to undergo baseline assessments of muscle function
      (including one-repetition maximum (1RM) strength tests to set the load for subsequent
      training sessions), body composition, muscle size, and muscle fibre pennation to monitor the
      effectiveness of the pre-training exercise intervention on the day of the second
      familiarisation session.

      Participants in the PT group will attend ten resistance training sessions across four weeks
      prior to the 14-day step-reduction, with sessions separated by at least 48 hours. The last
      training session will take place three days before the first main trial pre-step-reduction.
      All exercise sessions will be fully supervised by a member of the research team. At the
      beginning of the fifth session, participants will repeat the 1RM and incremental power tests.
      Repetitions will be performed at a cadence of 1:1 for extension:flexion time, at a
      participant-selected pace less that should be less than five seconds per complete repetition.
      Rest intervals between sets will be 90 to 120 seconds at the participant's discretion.

      Participants will complete the standardised warm-up on the Keiser leg press performed during
      the familiarisation session, using the most recent 1RM. All exercise sessions will include
      leg press and leg extension exercises, followed by either dumbbell calf raises, and dumbbell
      curl and press, or dumbbell lateral raises, and seated lateral pull down with resistance
      bands.

      Main Trials taking place on the day before and day after the two-week step-reduction:

      Participants will be asked to report to the laboratory after a 10-hour overnight fast wearing
      light clothing with no metal components. Measures of the participant's height, weight, and
      waist circumference will be determined. Body composition will be assessed using a whole body
      dual-energy X-ray absorptiometry scan (DEXA), and a peripheral quantitative computed
      tomography scan (pQCT) of the calf and thigh, and an ultrasound scan of the calf and thigh
      will be conducted. The pQCT and ultrasound will be taken from the dominant leg. Resting
      samples of subcutaneous adipose tissue via biopsy techniques and venous blood via cannula
      will then be obtained. Participants will ingest 200 ml of D20 and undertake a mixed meal
      tolerance test whilst remaining rested in a comfortable bed or armchair for three hours with
      blood samples drawn intermittently through the cannula. A short lunch break will then be
      taken. Thereafter a thigh muscle biopsy will be sampled, and then participants will undertake
      balance testing as performed in the familiarisation, whilst wearing Xsens 3D accelerometers
      on the foot, shin, and thigh with adhesive pads and being filmed with two video cameras to
      record footage for later kinematic analysis. The standard leg pressing warm-up using the
      previously obtained 1-RM, and the incremental power test described above as a measure of leg
      strength and power will then be performed. Following two minutes of recovery, participants
      will complete the assessment of neural drive of the calf muscle, followed by three sets of
      eight repetitions at 70% 1RM on the leg press and leg extension (total of 48 repetitions).
      This protocol is used to stimulate the stress response to exercise, so blood samples will be
      taken immediately after the exercise is complete with a muscle biopsy obtained from the
      contralateral leg after 90-minutes of seated rest post exercise. Whilst the participant
      rests, they will be asked to complete two questionnaires (The Pittsburgh Sleep Quality Index,
      and World Health Organization Quality of Life questionnaire (WHOQOL-BREF)). Participants in
      the ES group will then be given a demonstration of the exercise snacking regime, and be asked
      to complete a bout of the exercise, and shown how to use their exercise snacking log book.

      Step-reduction:

      For the next 14-days participants will be asked to restrict their daily step count to no more
      than 1500 steps per day. A portable pedometer will be worn by subjects at all times
      throughout the day (excluding sleep) to allow accurate monitoring and feedback of step count.
      Participants in the ES group will be asked to record number of steps before and after each
      bout of exercise snacking exercise thus steps taken during the exercise snack can be excluded
      from the daily 1,500 steps limit. Participants will also wear a physical activity monitor
      throughout the first week of the intervention. They will be asked to record their dietary
      intake on the 1st, 7th and 13th days of the step-reduction intervention using a dietary
      diary.

      Other assessments:

      Biopsy 1: On the third day of the 14-day step-reduction, a resting muscle biopsy and blood
      sample will be taken. Transport arrangements will be made to reduce ambulation for the
      purpose of the visit. Participants in the ES group will be asked to perform an exercise snack
      in the laboratory.

      Biopsy 2: On the eighth day of the 14-day step-reduction, another muscle biopsy and blood
      sample will be taken, and 100 ml dose of D20 ingested.

      Follow up biopsy: Three days after the 14-day step-reduction, a final muscle biopsy and blood
      sample will be taken.

      Exercise Snacking regime:

      The exercise snacking requires only a stable kitchen chair to perform, and no supervision is
      necessary though three bouts will be performed in the laboratory. Participants will be asked
      to perform five exercises, each for one minute followed by one minute of rest. In that minute
      of exercise, the participant will perform as many controlled repetitions of the exercise as
      they can. Participants will be asked to perform the exercise snacks three times daily,
      separated by at least two hours where possible. The exercises are: sit-to-stand from a chair,
      seated knee extension, standing knee bends, marching on the spot, and standing calf raises. A
      chair can be held for stability if needed. Participants will always perform the sit-to-stand
      exercise first, and record the number of repetitions completed in the minute, and thereafter
      participants may alternate the order of exercises, but will be asked to record the order in a
      log book provided.

      Re-training:

      After the step-reduction participants will attend six resistance training sessions over
      14-days with sessions separated by at least 48 hours, with the first training session taking
      place on the day of the follow up biopsy once the sample has been taken. These sessions will
      take place in the laboratory, supervised by a member of the research team, and will follow
      the same training regime as the PT group undertook prior to commencing the step-reduction.
      Thereafter, participants will be offered six weeks of further re-training supervised by a
      qualified personal trainer, training two times per week in the University Sports Training
      Village.

      Post re-training muscle size, strength, power, and balance assessments:

      Follow-up assessments of muscle function, balance, and muscle size and architecture will be
      made two days after the final session of the two-week laboratory based re-training, and where
      applicable two-days after the optional six-week gym based re-training (optional). These
      assessments will be DEXA, pQCT and ultrasound scans, and the leg press incremental power
      test, test of neural drive, and balance and movement pattern assessments.

      Qualitative assessment of well-being and quality of life:

      Following or during the intervention each participant will be invited to take part in an
      interview to provide feedback on his experience during the trial. Participants will be
      provided with written information of the purpose of the interviews (i.e., to inform the
      feasibility of the protocols) and reassured that participation is optional. Interviews will
      take place via telephone or in person according to participant preference, will be digitally
      recorded, transcribed verbatim and anonymized on completion. The interview schedule will
      cover; (i) participants' perceptions of the impact of inactivity on mood, appetite, vitality,
      sleep and other participant-generated concerns (for comparison across conditions), (ii)
      adherence to the study protocol (i.e., if and how participants adapted the prescribed
      regimes, and factors they suggest would make the protocol easier to adopt), and (iii)
      participants in the exercise snacking condition will additionally be asked to discuss the
      perceived barriers and facilitators, and costs and benefits of exercise-snacking. Transcripts
      will be analysed systematically using framework analysis to highlight key themes within and
      across participants, and the results used to facilitate participant input into the
      feasibility analysis and protocol amendments.
    

Intervention name(s): Step-reduction; Pre-training; Exercise snacking
Intervention type(s): Behavioral; Behavioral; Behavioral
Intervention description(s): Participants will reduce the number of steps they take each day to less than 1, 500 for two weeks, using a pedometer to monitor their daily step count.; Participants will attend 10 strength training exercise sessions over a four week period prior to the step-reduction intervention. These exercise sessions will be focused on lower limb strength, fully supervised and will be progressive.; Participants will perform three bouts of five minutes of exercise each day during the two week step-reduction intervention. These will consist of five discrete exercises, each performed continuously for one minute, with one minute of rest between each exercise. These exercises will be non-supervised, and require no specialist equipment.
Other intervention name(s): Reduced physical activity
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Step-reduction model; Reduced activity; Atrophy; Skeletal Muscle; Sarcopenia; Dynapenia