FIT Exercise in 30d of ULLS-induced Muscle Disuse

NCT06631053 | Recruiting

• 2 other identifiers: 9728980NSSC24M0149
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Muscle Atrophy; Muscle Weakness

Keywords

spaceflight; unweighting; disuse; exercise

Outcome Measures

Primary Outcomes (19)

• 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 Outcomes (11)

• Aerobic Capacity

  Baseline and day 30

• Ventilatory Threshold

  Baseline and day 30

• Substrate utilization

  Baseline and day 30

• Body Composition

  Baseline and day 30

• Postural sway area

  Baseline, day 13, and day 30

Study Arms (2)

No Exercise

ACTIVE COMPARATOR

Participants will undergo a 30d Unilateral Lower Limb Suspension (ULLS) without exercise

Other: No Exercise

velocity-based FIT (VBFIT)

EXPERIMENTAL

Participants will undergo a 30d Unilateral Lower Limb Suspension (ULLS) with exercise

Other: velocity-based FIT (VBFIT)

Interventions

velocity-based FIT (VBFIT) OTHER

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

velocity-based FIT (VBFIT)

No Exercise OTHER

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.

No Exercise

Eligibility Criteria

• Age: 35 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Lance Bollinger: lead
• University of Louisville: collaborator
• National Aeronautics and Space Administration (NASA): collaborator

Study Sites (1)

University of Kentucky

Lexington, Kentucky, 40506, United States

RECRUITING

MeSH Terms

Conditions

Muscular Atrophy; Muscle Weakness; Motor Activity

Condition Hierarchy (Ancestors)

Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Muscular Diseases; Musculoskeletal Diseases; Pathologic Processes; Behavior

Study Officials

• Lance Bollinger, PhD

  University of Kentucky

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lance Bollinger, PhD

CONTACT

8592577904; lance.bollinger@uky.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Participants are unable to be masked to their intervention (exercise v. non-exercise). Although other researchers from this team will be responsible for directly implementing exercise interventions, exercise sessions will be conducted in the same building as the PI's office. Therefore, it is likely that the PI will be aware of which subjects are completing exercise sessions. The PI and his team will be directly responsible for assessing primary and secondary research outcomes.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Model Details: 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.

Study Record Dates

• First Submitted: September 24, 2024
• First Posted: October 8, 2024
• Study Start: October 23, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: October 24, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)