NCT05801185

Single Nuclei Sequencing in Human Skeletal Muscle After Unloading

• Status: Enrolling By Invitation
• Phase: N/A
• Study type: Interventional
• Enrollment: 10 (estimated)
• Sponsor: Karolinska Institutet · Academic / Other
• Sex: Male
• Age: 18 Years – 40 Years
• Healthy volunteers: Accepted

Summary

Injuries often require people to undergo some degree of limb immobilization. This comes at a high cost in terms of muscle mass and function losses. At the molecular level, it is completely unknown how the different cells in the muscle respond to this complete lack of mechanical stimuli. The investigators will explore cell type specific changes in skeletal muscle after a short period of unloading, and specifically examine the behavior of myogenic stem cells with particular attention to potential unloading-induced maturation into fast- or slow-twitch muscle fibers. Ten healthy young participants will perform a 5-day Unilateral Lower Limb Suspension (ULLS) intervention, where one leg is continuously subjected to unloading, i.e., lack of mechanical stimuli. Before and after the ULLS period, participants will perform muscle function testing and MRI scans to assess muscle size in the lower limbs. Immediately after the ULLS, two muscle biopsies will be obtained, one from each leg. The tissue will be employed for single-nuclei RNA sequencing analysis and immunohistochemistry experiments. This project will be the first to analyze cell type specific changes induced by complete, short-term lack of mechanical stimuli in skeletal muscle. This will add a new dimension to the understanding of the processes directing this type of muscle atrophy (i.e., muscle loss in otherwise healthy individuals) and thus help to develop effective countermeasures to offset muscle changes.

Conditions

• Unilateral Lower Limb Suspension

Interventions

Type	Name	Description
OTHER	Unilateral lower limb suspension	Participants will perform a 5-day unloading intervention using the ULLS model. Short-length crutches, aided by handgrip and forearm support distal to the elbow will be used to assist in any upright or ambulatory activity. One foot (randomized in a counterbalance manner) will be equipped with a shoe having a 10-cm thick sole, which permits the unloaded limb to move passively about the hip joint while adopting a near straight position.

Timeline

• Start date: 2023-03-05
• Primary completion: 2024-12-01
• Completion: 2025-08-01
• First posted: 2023-04-06
• Last updated: 2024-06-21

Locations

1 site across 1 country: Sweden