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

NCT04128566 | Completed

• 1 other identifier: 2019-01315;ch19Muendermann3
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Articular Cartilage Degeneration

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

Outcome Measures

Primary Outcomes (6)

• 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

  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)

• 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

  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)

• 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

  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)

• 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

  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)

• 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

  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)

• 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

  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)

• Change in modified Knee Society Score (KSS) score

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

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

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

• Change in Physical activity (PA) level

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

• Joint kinematics and kinetics

  during the Walking stress test (t0= Baseline)

• Change in heart rate (beats per minute)

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

Study Arms (4)

Group 1: healthy subjects aged between 20 and 30 years

EXPERIMENTAL

healthy subjects aged between 20 and 30 years

Procedure: walking stress test

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

EXPERIMENTAL

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

Procedure: walking stress test

Group 3: healthy subjects aged between 40 and 60 years

EXPERIMENTAL

healthy subjects aged between 40 and 60 years

Procedure: walking stress test

previous ACL injury aged between 40 and 60 years

EXPERIMENTAL

subjects with previous ACL injury aged between 40 and 60 years

Procedure: walking stress test

Interventions

walking stress test 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 1: healthy subjects aged between 20 and 30 years; Group 2: previous ACL injury aged between 20 and 30 years; Group 3: healthy subjects aged between 40 and 60 years; previous ACL injury aged between 40 and 60 years

Eligibility Criteria

• Age: 20 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead
• Swiss National Science Foundation: collaborator

Study Sites (1)

Department of Orthopaedics and Traumatology, University Hospital Basel

Basel, 4031, Switzerland

Location

Related Publications (2)

• 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.

  PMID: 37263066 DERIVED

• 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.

  PMID: 35984848 DERIVED

MeSH Terms

Conditions

Wounds and Injuries

Study Officials

• Annegret Muendermann, Prof. Dr.

  Department of Orthopaedics and Traumatology, University Hospital Basel

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: 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.
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2019
• First Posted: October 16, 2019
• Study Start: January 8, 2020
• Primary Completion: July 7, 2024
• Study Completion: July 7, 2024
• Last Updated: December 27, 2024

Record last verified: 2024-12

Locations

CH (1)