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Articular Cartilage DegenerationMechSensNCT04128566

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

A study testing walking stress test in people with Articular Cartilage Degeneration, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 20 to 60 yearsHealthy volunteers can take part
Conditions the study is for
Articular Cartilage Degeneration
What is being tested?
walking stress test
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
87 participants
Where
1 siteSwitzerland
Study dates
8 Jan 2020to 7 Jul 2024
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 to 60 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 17Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Switzerland1 site

  • Department of Orthopaedics and Traumatology, University Hospital Basel

    Basel, 4031

Other trials in Switzerland

About this study

Official title: MechSens - Dose-response Relationship of in Vivo Ambulatory Load and Mechanosensitive Cartilage Biomarkers: the Role of Age and Tissue Health

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.

Read the detailed 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 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.

Being tested
walking stress test
Keywords
articular cartilage, mechanosensitive blood markers of articular cartilage, walking stress test, ambulatory load, articular cartilage thinning, anterior cruciate ligament (ACL) injury, articular cartilage quality
Medical subject headings
Wounds and Injuries

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • walking stress testProcedure or surgery

    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.

Study groups in NCT04128566
Study groupRoleWhat they receive
Group 1: healthy subjects aged between 20 and 30 yearsExperimentalhealthy subjects aged between 20 and 30 years
Receives: Procedure: walking stress test
Group 2: previous ACL injury aged between 20 and 30 yearsExperimentalsubjects with previous Anterior cruciate Ligament (ACL) injury aged between 20 and 30 years
Receives: Procedure: walking stress test
Group 3: healthy subjects aged between 40 and 60 yearsExperimentalhealthy subjects aged between 40 and 60 years
Receives: Procedure: walking stress test
previous ACL injury aged between 40 and 60 yearsExperimentalsubjects with previous ACL injury aged between 40 and 60 years
Receives: Procedure: walking stress test

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in serum levels of Interleukin 6 (IL-6), ( mechanosensitive blood marker of articular cartilage) in pg/ml

    Change in serum level of Interleukin 6 (IL-6), (mechanosensitive blood marker of articular cartilage) in pg/ml

    Measured: Before walking stress test (t0= Baseline), immediately after walking stress test (t1), 30-minutes after walking stress test (t2) and after two additional 90-minute resting intervals after walking stress test (t3 and t4)

  2. Change in serum levels of Cartilage oligomeric matrix Protein (COMP) (mechanosensitive blood marker of articular cartilage) in U/l

    Change in serum levels of Cartilage oligomeric matrix Protein (COMP) (mechanosensitive blood marker of articular cartilage) in U/l

    Measured: Before walking stress test (t0= Baseline), immediately after walking stress test (t1), 30-minutes after walking stress test (t2) and after two additional 90-minute resting intervals after walking stress test (t3 and t4)

  3. Change in serum levels of Matrix metallopeptidase (MMP)-3 (mechanosensitive blood marker of articular cartilage) in ng/ml

    Change in serum levels of Matrix metallopeptidase (MMP)-3 (mechanosensitive blood marker of articular cartilage) in ng/ml

    Measured: Before walking stress test (t0= Baseline), immediately after walking stress test (t1), 30-minutes after walking stress test (t2) and after two additional 90-minute resting intervals after walking stress test (t3 and t4)

  4. Change in serum levels of Matrix metallopeptidase (MMP)-9 (mechanosensitive blood marker of articular cartilage) in ng/ml

    Change in serum levels of Matrix metallopeptidase (MMP)-9 (mechanosensitive blood marker of articular cartilage) in ng/ml

    Measured: Before walking stress test (t0= Baseline), immediately after walking stress test (t1), 30-minutes after walking stress test (t2) and after two additional 90-minute resting intervals after walking stress test (t3 and t4)

  5. Change in serum levels of Proteoglycan (PGR)-4 (mechanosensitive blood marker of articular cartilage) in mg/ml

    Change in serum levels of Proteoglycan (PGR)-4 (mechanosensitive blood marker of articular cartilage) in mg/ml

    Measured: Before walking stress test (t0= Baseline), immediately after walking stress test (t1), 30-minutes after walking stress test (t2) and after two additional 90-minute resting intervals after walking stress test (t3 and t4)

  6. Change in serum levels of A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-4) (mechanosensitive blood marker of articular cartilage) in ng/mL

    Change in serum levels of A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-4) (mechanosensitive blood marker of articular cartilage) in ng/mL

    Measured: Before walking stress test (t0= Baseline), immediately after walking stress test (t1), 30-minutes after walking stress test (t2) and after two additional 90-minute resting intervals after walking stress test (t3 and t4)

Secondary outcomes (7)

  1. Change in modified Knee Society Score (KSS) score

    KSS consists of a total of 34 questions divided into four subscales which are rated separately. It consists of a Knee Score, which only rates the knee joint itself (e.g. pain, range of motion, stability and radiographic alignment), and a Function Score (patient's walking distance, climbing stairs and use of walking aids). The higher the score, the better the outcome in all subscales.

    Measured: Before walking stress test (t0= Baseline), at 12-month follow-up, at 24-month follow-up

  2. Change in modified Knee Injury and Osteoarthritis Outcome Score (KOOS) score

    The KOOS evaluates both short-term and long-term consequences of knee injury. It holds 42 items in 5 separately scored subscales; Pain, other Symptoms, Function in daily living (ADL), Function in Sport and Recreation (Sport/Rec), and knee-related Quality of Life (QOL). The five KOOS subscales rate on a 5-point Likert-scale as extremely important, very important, moderately important, somewhat important, or not important at all.

    Measured: Before walking stress test (t0= Baseline), at 12-month follow-up, at 24-month follow-up

  3. Change in Physical activity (PA) level

    PA level ( number of steps taken, PA intensity) will be recorded using an activity monitor (ActiGraph GT3X+, Pensacola, FL, USA)

    Measured: during the 7 days prior to Baseline and during the Walking stress test (t0= Baseline)

  4. Joint kinematics and kinetics

    For the the three loading conditions at the Walking stress test, an inertial sensor system (RehaGait®, Hasomed GmbH, Magdeburg, Germany) will be used to collect joint angle curves at the ankle, knee and hip.

    Measured: during the Walking stress test (t0= Baseline)

  5. Change in heart rate (beats per minute)

    To assess and compare the cardiovascular stress subjects experience during the walking stress tests the heart rate will be measured.

    Measured: During the walking stress test until 10 minutes after the stress test

  6. Change in T2 relaxation time from baseline to follow-up

    Tissue status will be determined by the T2 relaxation time of weight bearing knee cartilage analyzed by Magnetic resonance Imaging (MRI) of both knees

    Measured: MRI at least 7 days prior to the Walking stress test (t0= Baseline) and MRI 24 months after baseline

  7. Change in cartilage thickness from baseline to follow-up

    Tissue status will be determined by the thickness of weight bearing knee cartilage analyzed by Magnetic resonance Imaging (MRI) of both knees

    Measured: MRI at least 7 days prior to the Walking stress test (t0= Baseline) and MRI 24 months after baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Oct 2019
  2. Study start8 Jan 2020
  3. Primary completion7 Jul 2024
  4. Study completion7 Jul 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Diagnosis
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
87 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04128566
Sponsor's protocol ID
2019-01315;ch19Muendermann3
Other IDs
2019
Acronym
MechSens
Status last verified
Dec 2024
First submitted
3 Oct 2019
Last updated
27 Dec 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 37263066

  • 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.

    PubMed 35984848

Questions about this trial

What is this clinical trial studying?

A study testing walking stress test in people with Articular Cartilage Degeneration, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in serum levels of Interleukin 6 (IL-6), ( mechanosensitive blood marker of articular cartilage) in pg/ml (time frame: Before walking stress test (t0= Baseline), immediately after walking stress test (t1), 30-minutes after walking stress test (t2) and after two additional 90-minute resting intervals after walking stress test (t3 and t4)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04128566, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Dec 2024.

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