FIT Exercise in 30d of ULLS-induced Muscle Disuse

Use of Velocity Monitoring to Prescribe Appropriate Flywheel-based Inertial Training (FIT) Workloads for Exercise in Space Flight

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.

Study Overview

• Status: Recruiting
• Conditions: Muscle Weakness; Muscle Atrophy
• Intervention / Treatment: Other: No Exercise; Other: velocity-based FIT (VBFIT)

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

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lance Bollinger, PhD; Phone Number: 8592577904; Email: lance.bollinger@uky.edu

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40506
      • Recruiting
      • University Of Kentucky

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: No Exercise; Participants will undergo a 30d Unilateral Lower Limb Suspension (ULLS) without exercise	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.
Experimental: velocity-based FIT (VBFIT); Participants will undergo a 30d Unilateral Lower Limb Suspension (ULLS) with exercise	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Voluntary activation	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.	Baseline, day 13, and day 30
Twitch Properties-Electromechanical Delay	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.	Baseline, day 13, and day 30
Twitch Properties-Rate of Torque Development	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.	Baseline, day 13, and day 30
Twitch Properties-Time to peak Tension	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.	Baseline, day 13, and day 30
Twitch Properties-Peak Twitch Torque	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.	Baseline, day 13, and day 30
Twitch Properties-Relaxation Rate	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.	Baseline, day 13, and day 30
Post activation Potentiation	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.	Baseline, day 13, and day 30
Motor unit action potential train (MUAPT) firing rate	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.	Baseline, day 13, and day 30
Motor unit action potential train (MUAPT) recruitment threshold.	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.	Baseline, day 13, and day 30
Motor unit action potential train (MUAPT) de-recruitment threshold.	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.	Baseline, day 13, and day 30
Muscle size	Muscle size will be measured by MRI. Anatomical MRI scans will allow for assessment of anatomical cross sectional area.	Baseline and day 30
Muscle Physiological cross-sectional area	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.	Baseline and day 30
Muscle Fractional Anisotropy	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.	Baseline and day 30
Muscle Diffusion properties	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).	Baseline and day 30
Muscle cross-sectional area (Ultrasound)	cross-sectional area of the vastus lateralis and rectus femoris will be measured by ultrasonography	Baseline, day 13, and day 30
Fascicle length	Panoramic views of the mid-portion of the VL will be measured by ultrasonography	Baseline, day 13, and day 30
Pennation angle	Pennation angle of the mid-portion of the vastus lateralis will be assessed by ultrasonography	Baseline, day 13, and day 30
Voluntary Isokinetic Muscle Strength	Maximal voluntary isokinetic concentric strength of the knee extensors/flexors and ankle dorsi-/plantar-flexors will be assessed at 60 deg/s	Baseline, day 13, and day 30
Voluntary Isometric Muscle Strength	Maximal voluntary isometric strength of the knee extensors/flexors and ankle dorsi-/plantar-flexors will be assessed during a (10 seconds) maximal effort contraction.	Baseline, day 13, and day 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aerobic Capacity	Subjects will complete a VO2max exercise test on a stationary bicycle. Gas exchange and heart rate data will be collected continuously. Initial workload will be set at approximately 2 METS. Every three minutes, we will add more resistance to the pedals (~1.5 METS). Subjects will continue to pedal until they can either not maintain pedal speed (50RPM) or until a plateau in VO2 occurs. Pedal force for each limb will be assessed.	Baseline and day 30
Ventilatory Threshold	Gas exchange data from the aerobic capacity test (VO2, ventilation; VE, and VCO2) will be used to calculate ventilatory threshold during exercise	Baseline and day 30
Substrate utilization	Gas exchange data from the aerobic capacity test (VO2, respiratory exchange ratio; RER, and VCO2) will be used to calculate substrate utilization (energy expenditure, carbohydrate use, and fatty acid oxidation) at varying exercise intensities	Baseline and day 30
Body Composition	Bioelectrical Impedance Analysis (BIA) will be used to assess body composition. Subjects will lie supine and have small adhesive electrodes placed on the right hand, wrist, ankle, and foot. A small (imperceptible) electrical current will be delivered to one electrode and the amount of resistance to the electrical current will be used to measure body composition. Percent body fat will be measured. Muscle mass will be calculated using previously established formulae.	Baseline and day 30
Postural sway area	Subjects will complete a series of balance assessments while standing on one leg using a dual force plate system. Subjects will stand still on one leg for 15 seconds with hands on hips. This will be repeated on both legs with eyes open and with eyes closed in the shod and unshod conditions in random order. Postural sway area will be calculated as an index of postural control.	Baseline, day 13, and day 30
Postural Sway Velocity	Subjects will complete a series of balance assessments while standing on one leg using a dual force plate system. Subjects will stand still on one leg for 15 seconds with hands on hips. This will be repeated on both legs with eyes open and with eyes closed in the shod and unshod conditions in random order. Mean Postural sway velocity will be calculated as an index of postural control.	Baseline, day 13, and day 30
Motor unit firing rate - single leg stance	Subjects will complete a series of balance assessments while standing on one leg using a dual force plate system. Subjects will stand still on one leg for 15 seconds with hands on hips. This will be repeated on both legs with eyes open and with eyes closed in the shod and unshod conditions in random order. High density surface EMG sensors will be adhered to the skin over the tibialis anterior and soleus muscles with double-sided tape. Exponential functions will be fit to describe the relationship between motor unit firing rate and action potential amplitude on an individual manner to determine how firing rates of various motor unit pools relate to postural control.	Baseline, day 13, and day 30
Change in heart rate at rest	heart rate measured	Baseline and day 30
Change in blood pressure at rest	blood pressure measured at the arm	Baseline and day 30
Change in heart rate variability	for 20 minutes electrodes will be placed on the skin of the chest and a respiratory belt will be wrapped around the chest and blood pressure will be taken at the arm. During the final 10 minutes, 5 minutes of regular breathing (minutes 11-15), and 5 minutes of controlled breathing at a rate of 12 breaths per minute will be done. Resting heart rate (throughout), respiratory rate (throughout) and blood pressure (min 15 and 20) will be collected.	Baseline and day 30
Change in heart rate recovery after exercise	a maximal-effort exercise test on a stationary bicycle will be done. Immediately upon finishing the cycling, participants will rest on the bike for 5 minutes while remaining as still as possible. Heart rate will be collected throughout the this time to give a measure of heart rate recovery	Baseline and day 30

Collaborators and Investigators

• Sponsor: Lance Bollinger
• Collaborators: University of Louisville; National Aeronautics and Space Administration (NASA)
• Investigators: Principal Investigator: Lance Bollinger, PhD, University Of Kentucky

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: September 24, 2024
• First Submitted That Met QC Criteria: October 5, 2024
• First Posted (Actual): October 8, 2024

Study Record Updates

• Last Update Posted (Estimated): October 24, 2025
• Last Update Submitted That Met QC Criteria: October 22, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: exercise; spaceflight; disuse; unweighting
• Additional Relevant MeSH Terms: Neurologic Manifestations; Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Manifestations; Pathologic Processes; Pathological Conditions, Anatomical; Atrophy; Pathological Conditions, Signs and Symptoms; Behavior; Signs and Symptoms; Muscle Weakness; Muscular Atrophy; Motor Activity
• Other Study ID Numbers: 97289; 80NSSC24M0149 (Other Grant/Funding Number: NASA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No