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

NCT ID: NCT04128566

Last Updated: 2024-12-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

87 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-01-08

Study Completion Date

2024-07-07

Brief Summary

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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.

Detailed Description

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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 addressed:

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.

Conditions

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Articular Cartilage Degeneration

Keywords

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articular cartilage mechanosensitive blood markers of articular cartilage walking stress test ambulatory load articular cartilage thinning anterior cruciate ligament (ACL) injury articular cartilage quality

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Blinding to the experimental condition is not possible because of the obvious differences between conditions (partial weight bearing and additional load). However, the person processing the data will be blinded to the condition.

Study Groups

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Group 1: healthy subjects aged between 20 and 30 years

healthy subjects aged between 20 and 30 years

Group Type EXPERIMENTAL

walking stress test

Intervention Type PROCEDURE

walk for 30 minutes on a treadmill with either one of the three loading conditions (reduced load = 80% Bodyweight (BW), normal load = 100% BW, increased load = 120% BW). The order of experimental condition will be applied in randomized order determined by block randomization, and the same self-selected walking speed will be used for all conditions.

Group 2: previous ACL injury aged between 20 and 30 years

subjects with previous Anterior cruciate Ligament (ACL) injury aged between 20 and 30 years

Group Type EXPERIMENTAL

walking stress test

Intervention Type PROCEDURE

walk for 30 minutes on a treadmill with either one of the three loading conditions (reduced load = 80% Bodyweight (BW), normal load = 100% BW, increased load = 120% BW). The order of experimental condition will be applied in randomized order determined by block randomization, and the same self-selected walking speed will be used for all conditions.

Group 3: healthy subjects aged between 40 and 60 years

healthy subjects aged between 40 and 60 years

Group Type EXPERIMENTAL

walking stress test

Intervention Type PROCEDURE

walk for 30 minutes on a treadmill with either one of the three loading conditions (reduced load = 80% Bodyweight (BW), normal load = 100% BW, increased load = 120% BW). The order of experimental condition will be applied in randomized order determined by block randomization, and the same self-selected walking speed will be used for all conditions.

previous ACL injury aged between 40 and 60 years

subjects with previous ACL injury aged between 40 and 60 years

Group Type EXPERIMENTAL

walking stress test

Intervention Type PROCEDURE

walk for 30 minutes on a treadmill with either one of the three loading conditions (reduced load = 80% Bodyweight (BW), normal load = 100% BW, increased load = 120% BW). The order of experimental condition will be applied in randomized order determined by block randomization, and the same self-selected walking speed will be used for all conditions.

Interventions

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walking stress test

walk for 30 minutes on a treadmill with either one of the three loading conditions (reduced load = 80% Bodyweight (BW), normal load = 100% BW, increased load = 120% BW). The order of experimental condition will be applied in randomized order determined by block randomization, and the same self-selected walking speed will be used for all conditions.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* Being physically active (\>2hours/week)
* No previous known knee injury:


* 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
Minimum Eligible Age

20 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Swiss National Science Foundation

OTHER

Sponsor Role collaborator

University Hospital, Basel, Switzerland

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Annegret Muendermann, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Department of Orthopaedics and Traumatology, University Hospital Basel

Locations

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Department of Orthopaedics and Traumatology, University Hospital Basel

Basel, , Switzerland

Site Status

Countries

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Switzerland

References

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Kunzler M, Herger S, De Pieri E, Egloff C, Mundermann A, Nuesch C. Effect of load carriage on joint kinematics, vertical ground reaction force and muscle activity: Treadmill versus overground walking. Gait Posture. 2023 Jul;104:1-8. doi: 10.1016/j.gaitpost.2023.05.018. Epub 2023 May 19.

Reference Type DERIVED
PMID: 37263066 (View on PubMed)

Herger S, Vach W, Nuesch C, Liphardt AM, Egloff C, Mundermann A. Dose-response relationship of in vivo ambulatory load and mechanosensitive cartilage biomarkers-The role of age, tissue health and inflammation: A study protocol. PLoS One. 2022 Aug 19;17(8):e0272694. doi: 10.1371/journal.pone.0272694. eCollection 2022.

Reference Type DERIVED
PMID: 35984848 (View on PubMed)

Other Identifiers

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2019-01315;ch19Muendermann3

Identifier Type: -

Identifier Source: org_study_id