FIT Exercise in 30d of ULLS-induced Muscle Disuse

OTHER

velocity-based FIT (VBFIT)

Participants will ambulate unilaterally using a shoe modified with a 5cm rocker-style stack and forearm crutches for the duration of the study. All participants will complete two testing sessions prior to ULLS, one testing session at day 13, and two testing sessions at the end of the study. Those assigned to the exercise group will perform a both high-intensity resistance and aerobic exercise three times per week

OTHER

No Exercise

Participants will ambulate unilaterally using a shoe modified with a 5cm rocker-style stack and forearm crutches for the duration of the study. All participants will complete two testing sessions prior to ULLS, one testing session at day 13, and two testing sessions at the end of the study.

Voluntary activation

Time frame: Baseline, day 13, and day 30

Voluntary activation of the quadriceps will be assessed with electrical stimulation of the femoral nerve before, during, and after a maximal voluntary isometric contraction (MVIC) using the interpolated twitch technique.

Twitch Properties-Electromechanical Delay

Time frame: Baseline, day 13, and day 30

Electromechanical delay will be calculated as the time difference between the onset of electrical impulse and onset of torque development during femoral nerve stimulation. This will be measured before and after a maximal voluntary isometric contraction.

Twitch Properties-Rate of Torque Development

Time frame: Baseline, day 13, and day 30

Rate of Torque Development will be calculated as the change in torque divided by the change in time in the linear phase between 20 and 80% of peak twitch torque during femoral nerve stimulation. This will be measured before and after a maximal voluntary isometric contraction.

Twitch Properties-Time to peak Tension

Time frame: Baseline, day 13, and day 30

Time to peak tension will be calculated as the time difference between the onset of electrical impulse and peak twitch torque during femoral nerve stimulation. This will be measured before and after a maximal voluntary isometric contraction.

Twitch Properties-Peak Twitch Torque

Time frame: Baseline, day 13, and day 30

Peak twitch torque during femoral nerve stimulation will be calculated as the highest torque output immediately (approximately 200ms) following femoral nerve stimulation. This will be measured before and after a maximal voluntary isometric contraction.

Twitch Properties-Relaxation Rate

Time frame: Baseline, day 13, and day 30

Relaxation rate will be calculated as the change in torque divided by the change in time during the relaxation phase of twitch following femoral nerve stimulation. This will be measured before and after a maximal voluntary isometric contraction.

Post activation Potentiation

Time frame: Baseline, day 13, and day 30

Post-activation will be calculated as the percentage difference in peak twitch torque in femoral nerve stimulation before and after a maximal voluntary isometric contraction.

Motor unit action potential train (MUAPT) firing rate

Time frame: Baseline, day 13, and day 30

Firing rate of individual motor units of the vastus lateralis (VL) will be assessed with high density surface electromyography (EMG) using four-pin high density surface electromyography electrodes. Firing rate at 30, 60, and 90% MVIC will be reported. Motor unit firing rate will also be reported during static stance. Participants will use a screen displaying real-time torque output. Participants will voluntarily increase torque (5 seconds), hold at a pre-determined torque level (10 seconds), and gradually reduce force back to resting (5 seconds) with the knee held in a fixed position. This test will be completed with a 10s isometric hold at 30, 60, and 90% of maximal voluntary isometric force.

Motor unit action potential train (MUAPT) recruitment threshold.

Time frame: Baseline, day 13, and day 30

Recruitment threshold of individual motor units of the VL will be assessed with high density surface electromyography using four-pin high density surface electromyography electrodes. Recruitment threshold will be measured during isometric ramp contractions of the quadriceps Participants will use a screen displaying real-time torque output. Participants will voluntarily increase torque (5 seconds), hold at a pre-determined torque level (10 seconds), and gradually reduce force back to resting (5 seconds) with the knee held in a fixed position. This test will be completed with a 10s isometric hold at 30, 60, and 90% of maximal voluntary isometric force.

Motor unit action potential train (MUAPT) de-recruitment threshold.

Time frame: Baseline, day 13, and day 30

De-recruitment threshold of individual motor units f the VL will be assessed with high density surface electromyography using four-pin high density surface electromyography electrodes. Recruitment threshold will be measured during isometric ramp contractions of the quadriceps Participants will use a screen displaying real-time torque output. Participants will voluntarily increase torque (5 seconds), hold at a pre-determined torque level (10 seconds), and gradually reduce force back to resting (5 seconds) with the knee held in a fixed position. This test will be completed with a 10s isometric hold at 30, 60, and 90% of maximal voluntary isometric force.

Muscle size

Time frame: Baseline and day 30

Muscle size will be measured by MRI. Anatomical MRI scans will allow for assessment of anatomical cross sectional area.

Muscle Physiological cross-sectional area

Time frame: Baseline and day 30

Diffusion tensor imaging (DTI) will be used to assess muscle volume and fascicle length. Physiological cross-sectional area will be calculated as Muscle volume divided by fascicle length.

Muscle Fractional Anisotropy

Time frame: Baseline and day 30

Diffusion tensor imaging (DTI) will be used to assess anisotropic measures. A ratio of the diffusivity in the principal planes will be used to calculate fractional anisotropy.

Muscle Diffusion properties

Time frame: Baseline and day 30

Diffusion tensor imaging (DTI) will be used to assess rate of water diffusion in three principal planes. We will report rates of water diffusion in three ways: 1) mean diffusivity (average rate in all three plane), 2) axial diffusivity (rate of diffusion along primary axis), and 3) radial diffusivity (rate of diffusion perpendicular to the primary axis).

Muscle cross-sectional area (Ultrasound)

Time frame: Baseline, day 13, and day 30

cross-sectional area of the vastus lateralis and rectus femoris will be measured by ultrasonography

Fascicle length

Time frame: Baseline, day 13, and day 30

Panoramic views of the mid-portion of the VL will be measured by ultrasonography

Pennation angle

Time frame: Baseline, day 13, and day 30

Pennation angle of the mid-portion of the vastus lateralis will be assessed by ultrasonography

Voluntary Isokinetic Muscle Strength

Time frame: Baseline, day 13, and day 30

Maximal voluntary isokinetic concentric strength of the knee extensors/flexors and ankle dorsi-/plantar-flexors will be assessed at 60 deg/s

Voluntary Isometric Muscle Strength

Time frame: Baseline, day 13, and day 30

Maximal voluntary isometric strength of the knee extensors/flexors and ankle dorsi-/plantar-flexors will be assessed during a (10 seconds) maximal effort contraction.

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Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.

Will I receive a placebo instead of treatment?

When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.

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How long does a clinical trial last?

Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.