Unloaded Minds - How Prolonged Unloading Shapes Human Performance in Lunar Gravity

NCT07607340 | Recruiting

• 1 other identifier: 2025-02981-01 - UnloadedMinds
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

During spaceflight and lunar missions, reduced gravitational loading causes the muscles and nervous system to decondition rapidly. While muscle wasting is well documented, much less is known about how the brain and spinal cord adapt to the absence of normal mechanical loading - and how these central changes interact with muscle deterioration to impair movement control. This study investigates how two weeks of simulated lower limb unloading affects the brain's movement programs (motor engrams), the functional connection between nerves and muscles, and overall movement quality. Healthy participants undergo 14 days of Unilateral Lower Limb Suspension (ULLS), a model in which one leg is kept unloaded using a raised shoe and crutches while the other leg functions normally. After the unloading period, participants travel to Bordeaux, France, where they walk on a treadmill for the first time - in lunar gravity - during a parabolic flight. Before and after the unloading period, participants are assessed with MRI (muscle size), force plate tests (jump performance and balance), nerve stimulation (number of functional motor units), and treadmill gait analysis combining brain activity (EEG), muscle activity (EMG), joint movement, and plantar pressure measurements. The same gait analysis is repeated during the parabolic flight under lunar gravity (0.16G). The results will shed light on how the brain and muscles adapt to disuse and reactivate under partial gravity - with direct relevance to astronaut safety and rehabilitation, as well as clinical conditions involving prolonged limb immobilization.

Conditions

Unilateral Lower Limb Suspension (Simulated Microgravity)

Keywords

Unilateral lower limb suspension; Skeletal muscle; Motor engrams; Gait analysis; Space physiology

Outcome Measures

Primary Outcomes (1)

• Muscle volume

  Three days before the initiation of the ULLS intervention, and at day 15 of unloading, all participants will undergo an MRI scan to assess thigh and calf muscle size. Muscle volume will be evaluated using cross-sectional T2-weighted images acquired on a 3-Tesla MR system. Anatomical landmarks and standardized procedures will ensure that the same segment is scanned at both time points. Participants will rest in a supine position for approximately 30 minutes prior to each scan to minimize measurement interference caused by fluid shift. Images will be analysed using manual segmentation to delineate individual muscle boundaries in each cross-sectional slice; muscle volume is then calculated by summing the cross-sectional areas of the target muscles across all slices and multiplying by slice thickness.

  Three days before the initiation of the ULLS intervention and at day 15 of unloading, for both thigh and calf muscles bilaterally.

Secondary Outcomes (5)

• Gait analysis

  Gait analysis will be performed three-to-five days before the ULLS phase and during the lunar gravity phases of a parabolic flight

• Electroencephalogram

  Three-to-five days before the ULLS phase and during the lunar gravity phases of a parabolic flight, during the gait analysis tests.

• Electromyography

  Three-to-five days before the ULLS phase and during the lunar gravity phases of a parabolic flight, during the gait analysis tests.

• Muscle function and balance

  Three days before initiation of ULLS and immediately after the parabolic flight.

• Motor unit number estimation

  Three days before initiation of ULLS and immediately after the parabolic flight.

Study Arms (1)

ULLS

EXPERIMENTAL

There is only one arm, where one leg is the experimental, unloaded leg, and the other one is the control (loaded) leg

Behavioral: Unilateral lower limb suspension

Interventions

Unilateral lower limb suspension BEHAVIORAL

Unilateral Lower Limb Suspension (ULLS) is a validated spaceflight analog for the lower limbs, which mimics unloading specifically in the lower limbs 3. In ULLS, participants wear a shoe with \~100 mm elevated sole and use short-length crutches aided by a hand grip and forearm support distal to the elbow. This allows the contralateral lower limb to remain unloaded in a straight position and move passively at the hip. The ULLS model specifically targets skeletal muscle unloading in the lower limb with no or minor systemic deconditioning, and it imposes minimal restrictions on participants' daily activities. A key advantage of ULLS is that the contralateral, weight-bearing limb provides a valid inherent control accounting for individual factors such as nutrition, genetics, and lifestyle.

ULLS

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• \- 18-60 years of age, willing to participate

You may not qualify if:

• high activity level according to the GLTEQ
• contraindications to exercise
• pregnancy
• contraindications to MRI
• active cardiovascular disease
• cerebrovascular disease including previous stroke
• aneurysm (large vessels or intracranial)
• pulmonary disease including pulmonary hypertension or COPD
• metabolic diseases (including: hyper/hypoparathyroidism, hyper/hypothyroidism, Cushing's disease, type 1 or type 2 diabetes)
• active inflammatory bowel disease
• kidney disease
• malignancy
• recent steroid treatment (within the past 6 months), or hormone replacement therapy
• coagulation disorders
• musculoskeletal or neurological diseases

Sponsors & Collaborators

• Karolinska Institutet: lead
• German Sport University, Cologne: collaborator

Study Sites (1)

Karolinska Institutet

Huddinge, Stockholm County, 14152, Sweden

RECRUITING

Related Publications (6)

• Badali C, Wollseiffen P, Schneider S. Shades of gravity - effects of planetary gravity levels on electrocortical activity and neurocognitive performance. Brain Struct Funct. 2024 Jun;229(5):1265-1277. doi: 10.1007/s00429-024-02803-6. Epub 2024 May 3.

  PMID: 38700553 BACKGROUND

• Badali C, Wollseiffen P, Puck L, Klein T, Schneider S. Neurophysiological markers of cognitive workload under altered gravity conditions using a gamified dual-task paradigm. Sci Rep. 2026 Jan 9;16(1):1292. doi: 10.1038/s41598-025-34426-0.

  PMID: 41507273 BACKGROUND

• Fernandez-Gonzalo R, Irimia JM, Cusso R, Gustafsson T, Linne A, Tesch PA. Flywheel resistance exercise to maintain muscle oxidative potential during unloading. Aviat Space Environ Med. 2014 Jul;85(7):694-9. doi: 10.3357/asem.3856.2014.

  PMID: 25022156 BACKGROUND

• Tesch PA, Lundberg TR, Fernandez-Gonzalo R. Unilateral lower limb suspension: From subject selection to "omic" responses. J Appl Physiol (1985). 2016 May 15;120(10):1207-14. doi: 10.1152/japplphysiol.01052.2015. Epub 2016 Feb 4.

  PMID: 26846557 BACKGROUND

• Berg HE, Dudley GA, Haggmark T, Ohlsen H, Tesch PA. Effects of lower limb unloading on skeletal muscle mass and function in humans. J Appl Physiol (1985). 1991 Apr;70(4):1882-5. doi: 10.1152/jappl.1991.70.4.1882.

  PMID: 2055867 BACKGROUND

• Berg HE, Tesch PA. Changes in muscle function in response to 10 days of lower limb unloading in humans. Acta Physiol Scand. 1996 May;157(1):63-70. doi: 10.1046/j.1365-201X.1996.476217000.x.

  PMID: 8735655 BACKGROUND

Central Study Contacts

Rodrigo Fernandez Gonzalo, PhD, Research group leader

CONTACT

+46852483514; rodrigo.fernandez-gonzalo@ki.se

Mirko Mandic, PhD

CONTACT

+46700823625; mirko.mandic@ki.se

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD, Research group leader

Model Details: A well-validated spaceflight analgo is Unilateral Lower Limb Suspension (ULLS), which mimics unloading specifically in the lower limbs 3. In ULLS, participants wear a shoe with \~100 mm elevated sole and use short-length crutches aided by a hand grip and forearm support distal to the elbow. This allows the contralateral lower limb to remain unloaded in a straight position and move passively at the hip. The ULLS model specifically targets skeletal muscle unloading in the lower limb with no or minor systemic deconditioning, and it imposes minimal restrictions on participants' daily activities. A key advantage of ULLS is that the contralateral, weight-bearing limb provides a valid inherent control accounting for individual factors such as nutrition, genetics, and lifestyle.

Study Record Dates

• First Submitted: May 13, 2026
• First Posted: May 26, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): March 31, 2029
• Last Updated: May 26, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)