Clinical trial NCT06631053: FIT Exercise in 30d of ULLS-induced Muscle Disuse
Official title: Use of Velocity Monitoring to Prescribe Appropriate Flywheel-based Inertial Training (FIT) Workloads for Exercise in Space Flight
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Muscle Atrophy
Muscle Weakness
Keywords: spaceflight
unweighting
disuse
exercise
Lead sponsor: University of Kentucky
Sponsor class: OTHER
Collaborators: name: University of Louisville
name: National Aeronautics and Space Administration (NASA)
First posted: 2024-10-08
Enrollment: 16
Sex: ALL
Minimum age (years): 35
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: ULLS is the gold standard for assessing muscle disuse in ambulatory subjects. Velocity based resistance training and High Intensity Interval Training are gold-standard exercise strategies in terrestrial settings which tend to out-perform other exercise interventions. However, these exercise paradigms have not be applied to those undergoing unloading such as astronauts in space flight. Here, we aim to adopt principles from these established exercise interventions to determine their effectiveness in preserving muscle and aerobic fitness during 30d ULLS.
Primary purpose: TREATMENT

Brief summary: This study aims to determine how flywheel-based inertial training (FIT) implemented according to principles of velocity-based training (VBT) and High-Intensity Interval Training (HIIT) affects disuse-induced physical de-conditioning including loss of voluntary muscle strength, aerobic capacity, and balance regulation.

Detailed description: The primary objectives of this project are:

1. To assess how 30d of unilateral lower limb suspension (ULLS) with and without FIT exercise affects voluntary and electrically-evoked twitch force, motor unit recruitment, and anisotropic measures.
2. To determine how muscle anisotropy (assessed through diffusion tensor imaging) and motor unit action potential train (MUAPT) characteristics relate to contractile function in loaded and unloaded limbs

Secondary objectives include:

1. To assess impact of ULLS with and without FIT on aerobic capacity
2. To assess impact of ULLS with and without FIT on balance regulation during single-leg stance

This study aims to recruit 10 healthy, physically active participants (both male and female). Participants will undergo 30d of ULLS to unload the left limb during daily living activities. Subjects will wear a specially modified shoe with a 5cm rocker-style stack on the right leg and ambulate using crutches. Participants will be randomly assigned to either a control or exercise group. Those in the exercise group will perform Flywheel-based Inertial Training (FIT) leg press three times per week. Moment of inertia of the flywheel will be adjusted to elicit movement speeds of 0.4 m/s for resistance training (four sets of 10 repetitions). For High Intensity Interval Training, flywheel moment of inertia will be adjusted to elicit movement speed of 1.0m/s during upright squats (four sets of 3 min).

Before and after the intervention, subjects will complete a series of tests including:

1. Body Composition - height, weight, waist circumference, and tetrapolar bioelectrical impedance analysis will be conducted.
2. Balance assessment - center of pressure will be assessed using portable force decks during single leg stance with eyes open and closed. This test will be repeated in the shod and unshod conditions. MUAPT data (high density surface electromyography) will be collected for the soleus and tibialis anterior during this test.
3. Aerobic capacity test - VO2max will be determined during a graded exercise test on a cycle ergometer (3 min per stage). Gas exchange and heart rate data will be collected continuously throughout the test. Pedal force will also be assessed. Additional outcomes such as ventilatory threshold and substrate utilization will be assessed.
4. Muscle Imaging - Diffusion tensor imaging (DTI), a magnetic resonance technique will be used to assess anisotropic measures, muscle volume, fascicle length, and fascicle orientation of the mid-thigh.
5. Muscle strength testing - Maximal voluntary isometric and isokinetic strength of the knee extensors, flexors, and ankle plantar- and dorsi-flexors will be assessed. Interpolated twitch (electrical stimulation of the femoral nerve) will be used to assess twitch characteristics and voluntary activation of the quadriceps

Eligibility criteria: Inclusion Criteria:

* Regularly engaging in aerobic exercise (\> 150min/wk) and resistance exercise (\>1 time per week) for the past 12 months
* Education greater than or equal to bachelor's degree (any field)

Exclusion Criteria:

* Waist circumference \< 55cm or \> 90cm (F) and \< 75cm or \> 100cm (M)
* Body mass index \< 18.5 or \> 29.9
* Shoe size \< 25 or \>29cm.
* Not regularly engaging in exercise for previous 12 months
* Tobacco use within previous 6 months
* Blood clotting disorder
* Heart arrhythmia
* Implanted device which could negatively be affected by electrical impulse or strong magnetic field such as pacemaker, internal defibrillator, or cochlear implant
* Diagnosed cardiovascular, pulmonary, renal, or metabolic disease
* Pregnancy (within previous 6 months)
* Oral contraceptive use (within previous three months)
* High resting blood pressure (\>140 systolic and/or \> 90 diastolic)
* Currently or previously undergone gender-affirming therapy (hormone therapy or sexual reassignment surgery)
* Low back or leg injury in previous 6 months
* Currently taking medication to assist with sleep
* Muscle, bone, or joint injury that limits physical activity within previous 6 months
* Neurological disorder which affects balance (such as multiple sclerosis or Parkinson's disease)

Primary outcomes:
measure: Voluntary activation
timeFrame: Baseline, day 13, and day 30
measure: Twitch Properties-Electromechanical Delay
timeFrame: Baseline, day 13, and day 30
measure: Twitch Properties-Rate of Torque Development
timeFrame: Baseline, day 13, and day 30
measure: Twitch Properties-Time to peak Tension
timeFrame: Baseline, day 13, and day 30
measure: Twitch Properties-Peak Twitch Torque
timeFrame: Baseline, day 13, and day 30
measure: Twitch Properties-Relaxation Rate
timeFrame: Baseline, day 13, and day 30
measure: Post activation Potentiation
timeFrame: Baseline, day 13, and day 30
measure: Motor unit action potential train (MUAPT) firing rate
timeFrame: Baseline, day 13, and day 30
measure: Motor unit action potential train (MUAPT) recruitment threshold.
timeFrame: Baseline, day 13, and day 30
measure: Motor unit action potential train (MUAPT) de-recruitment threshold.
timeFrame: Baseline, day 13, and day 30
measure: Muscle size
timeFrame: Baseline and day 30
measure: Muscle Physiological cross-sectional area
timeFrame: Baseline and day 30
measure: Muscle Fractional Anisotropy
timeFrame: Baseline and day 30
measure: Muscle Diffusion properties
timeFrame: Baseline and day 30
measure: Muscle cross-sectional area (Ultrasound)
timeFrame: Baseline, day 13, and day 30
measure: Fascicle length
timeFrame: Baseline, day 13, and day 30
measure: Pennation angle
timeFrame: Baseline, day 13, and day 30
measure: Voluntary Isokinetic Muscle Strength
timeFrame: Baseline, day 13, and day 30
measure: Voluntary Isometric Muscle Strength
timeFrame: Baseline, day 13, and day 30
Secondary outcomes:
measure: Aerobic Capacity
timeFrame: Baseline and day 30
measure: Ventilatory Threshold
timeFrame: Baseline and day 30
measure: Substrate utilization
timeFrame: Baseline and day 30
measure: Body Composition
timeFrame: Baseline and day 30
measure: Postural sway area
timeFrame: Baseline, day 13, and day 30
measure: Postural Sway Velocity
timeFrame: Baseline, day 13, and day 30
measure: Motor unit firing rate - single leg stance
timeFrame: Baseline, day 13, and day 30
measure: Change in heart rate at rest
timeFrame: Baseline and day 30
measure: Change in blood pressure at rest
timeFrame: Baseline and day 30
measure: Change in heart rate variability
timeFrame: Baseline and day 30
measure: Change in heart rate recovery after exercise
timeFrame: Baseline and day 30
Other outcomes:
Locations:
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
Study officials:
affiliation: University of Kentucky
name: Lance Bollinger, PhD
role: PRINCIPAL_INVESTIGATOR
References: