MechSens - Dose-response Relationship of in Vivo Ambulatory Load and Mechanosensitive Cartilage Biomarkers

  • STATUS
    Recruiting
  • End date
    Nov 5, 2023
  • participants needed
    96
  • sponsor
    University Hospital, Basel, Switzerland
Updated on 5 February 2021

Summary

This study is to investigate the effects of age, tissue status and the presence of inflammation on the in vivo dose-response relationship of ambulatory load and mechanosensitive blood markers of articular cartilage.

Description

Articular cartilage is an avascular and aneural tissue that facilitates joint motion with minimal friction. Osteoarthritis (OA) is a joint disease that affects the whole joint resulting in severe articular cartilage degeneration with a prevalence worldwide of more than 10%. Although the molecular mechanisms that trigger the pathological changes in OA are largely unknown, the ability of chondrocytes to respond to load is believed to play a critical role in maintaining healthy tissue and in the initiation of OA. Different modes of ambulation have resulted in increases of specific blood markers, and immobilization during bed-rest lead to reductions in the same blood markers. However, the dose-response relationship between ambulatory load and mechanosensitive blood markers, its biological variation in healthy persons and in patients with a high risk of developing OA (e.g. with increasing age or after joint injury), and its relevance for cartilage degeneration are unknown. Based on reported differences in the magnitude of load-induced changes in blood markers of articular cartilage depending on the type of physical activity,an experimental framework of a systematic and controlled modulation of weight bearing during a walking stress test was previously tested and will be employed in this study. The following specific aims will be adressed:

Specific Aim 1: Investigate the in vivo dose-response relationship between ambulatory load and mechanosensitive blood markers of articular cartilage using controlled weight bearing during a walking stress test and age, tissue status and the presence of inflammation as experimental paradigms.

Specific Aim 2: Investigate the prognostic ability of the individual in vivo dose-response relationship between ambulatory load and mechanosensitive blood markers of articular cartilage for articular cartilage degeneration.

Healthy subjects and subjects with previous anterior cruciate ligament (ACL) injury aged 20 to 50 years will be clinically assessed, undergo magnetic resonance imaging (MRI) of both knees, and complete questionnaires on physical function and physical activity. Participants will wear an activity monitor for the 7 days before and during the experiment to record their physical activity level. Each participant will complete three walking stress tests (30 minutes walking) on separate days with repeated blood sampling to assess load-induced changes in levels of mechanosensitive blood markers (COMP, MMP-3, PRG-4, ADAMTS-4). In each test, one of three different ambulatory loads will be applied (80, 100 and 120% body weight (BW)). Inflammation will be assessed as IL-6 serum concentration. Tissue status of articular knee cartilage will be assessed as MRI T2 relaxation time and cartilage thickness at baseline and at 24-month follow-up.

Details
Condition Articular Cartilage Degeneration
Treatment walking stress test
Clinical Study IdentifierNCT04128566
SponsorUniversity Hospital, Basel, Switzerland
Last Modified on5 February 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Being physically active (>2hours/week)
No previous known knee injury
Inclusion Criteria for group 2 and 4
Being physically active (>2hours/week)
ACL rupture between 2 to 10 years prior to the study

Exclusion Criteria

Inability to provide informed consent
Age < 20 years (before maturation) or age > 60 years
Advanced general sarcopenia (degenerative loss of muscle mass in aging) and high likelihood of osteoarthritic changes
Body mass index (BMI) > 35 kg/m2
Excessive skin movement that influences the gait analysis
Inability to walk for 30 minutes
Contraindications for a knee MRI
Active rheumatic disorder
Prior neuromuscular impairment (e.g. stroke)
Conditions other than knee injury that could cause abnormal patterns of locomotion
Prior hip, knee, and ankle prosthesis
Osteotomy of the lower extremities - Prior spine surgery
Other major medical problems
Pregnancy
Investigators and their immediate families are not permitted to be subjects
Persons who have previously completed or withdrawn from this study
Patients currently enrolled in another experimental (interventional) protocol
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