Personalized Digital Training Intervention to Reduce Inflammation by Correcting Pathological Movement Patterns in Pre-stage Knee Osteoarthritis After Anterior Cruciate Ligament Reconstruction (PROTO-WP4)

Personalized Digital Training Intervention to Reduce Inflammation by Correcting Pathological Movement Patterns in Pre-stage Knee Osteoarthritis (OA)

Osteoarthritis (OA) is a condition that causes pain and stiffness in the joints, often due to injuries like torn ligaments. Even after surgery, these injuries can lead to long-term joint problems. Current treatments don't fully prevent OA from developing. This study is testing a new 12-week exercise program designed to improve how the knee moves, using a special sensor-based system. The goal is to reduce joint inflammation and prevent the development of OA in patients who have had knee surgery.

Study Overview

• Status: Recruiting
• Conditions: ACL Reconstruction; Osteoarthritis (OA) of the Knee
• Intervention / Treatment: Behavioral: Training intervention

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Winkler, Prof. Dr.med.; Phone Number: +49 30 450 559084; Email: tobias.winkler@charite.de

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Recruiting
    • Charité - Universitätsmedizin Berlin
    • Contact: Winkler, Prof.Dr.med.; Phone Number: +49 30 450 559084; Email: tobias.winkler@charite.de
  • Berlin, Germany, 10117
    • Recruiting
    • Charité - Universitätsmedizin Berlin, BeMoveD - Berlin Movement Diagnostics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Signed written informed consent
• Adult subjects between 18 to 50 years old at the time of screening
• Primary ACL reconstruction within a maximum of 6 months after a unilateral ACL injury
• Complete baseline assessment between 8 and 12 weeks after ACL reconstruction

Exclusion Criteria:

• Significant trauma to a weight-bearing joint within 12 months prior to study initiation (excluding the ACL injury)
• Previous surgeries on the study knee (except for the ACL reconstruction)
• Signs of knee OA as defined by the OARSI-Joint Space Narrowing (JSN) Score of two or more (standing AP x-ray)
• Physical activity level: Tegner activity score before injury of 0-2 (very low activity) or 8-10 (very high activity)
• Body mass index ≥ 30 kg/m2;
• Inflammatory arthropathies;
• Immunosuppression due to illness or medication;
• Sepsis or hemostasis disorders;
• Severe uncontrolled inflammatory disease or autoimmune disease (e.g., ulcerative colitis, Crohn's disease, etc.);
• Having malignancy and undergoing treatment including chemotherapy, radiotherapy, or immunotherapy;
• Contraindications for MRI, including pacemakers, defibrillators, metal implants, pregnancy, sensorineural hearing loss above 30 dB, tinnitus and claustrophobia
• Unable to freely give their informed consent (e.g., individuals under legal guardianship).
• Currently enrolled in or has not yet completed a period of at least 5 times as the half-life time of the drug used in the previous trial since ending other investigational device or drug trial(s)
• Patients who are dependent on the sponsor, investigator, or study site;
• Pregnant or breast-feeding women or women of childbearing potential not protected by an effective contraceptive method of birth control (defined as pearl index < 1);
• Any form of substance abuse, psychiatric disorder, or other condition that, in the opinion of the Investigator, may invalidate communication with the Investigator and/or designated study personnel;
• Patients who are committed to an institution by virtue of an order issued by either the judicial or the administrative authorities;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: The treatment group; In addition to the standard-of-care physiotherapy program, the treatment group will additionally receive a training intervention utilizing sensor-based technology that provides 3D avatar training, supported by an accompanying app, to deliver personalized exercise regimens. This intervention aims to correct the pathological knee movement and loading patterns that exacerbate joint inflammation and contribute to the development of knee OA.	Behavioral: Training intervention; Personalized digital training intervention aims to correct pathological knee movement and loading patterns and reduce inflammation in pre-stage knee osteoarthritis.
No Intervention: the control group; Standard-of-care physiotherapy program

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Endpoint	Restoration of normal knee angle and moment patterns during walking at 6-month follow-up (compared to normative data), as determined by a machine learning-derived gait index.	at 6-month follow-up visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Endpoint: Cartilage Thickness	Quantitative magnetic resonance imaging measurement of cartilage thickness, expressed in millimeters (mm), across predefined articular sub-regions of the knee.	Baseline, 6, and 36 months follow-up visits
Secondary Endpoint: Cartilage Volume	Quantitative magnetic resonance imaging measurement of cartilage volume, expressed in cubic millimeters (mm³), across predefined articular sub-regions of the knee.	Baseline, 6, and 36 months follow-up visits
Secondary Endpoint: Cartilage Composition	Quantitative magnetic resonance imaging measurement of cartilage composition using laminar T2 relaxation time, expressed in milliseconds (ms), reflecting cartilage water content and collagen organization across predefined articular sub-regions of the knee.	Baseline, 6, and 36 months follow-up visits
Secondary Endpoint: Meniscus Position	Quantitative magnetic resonance imaging measurement of meniscus extrusion, expressed in millimeters (mm), defined as the distance the meniscus extends beyond the edge of the tibial plateau.	Baseline, 6, and 36 months follow-up visits
Secondary Endpoint: Hoffa Synovitis	Quantitative magnetic resonance imaging measurement of Hoffa synovitis, expressed as a signal distribution pattern (dimensionless) within the infrapatellar (Hoffa's fat pad) region.	Baseline, 6, and 36 months follow-up visits
Secondary Endpoint: Effusion Synovitis	Quantitative magnetic resonance imaging measurement of joint effusion and synovitis, expressed as synovial fluid volume in cubic millimeters (mm³).	Baseline, 6, and 36 months follow-up visits
Secondary Endpoint: Magnetic Resonance Imaging Osteoarthritis Knee Score (MOAKS)	Semi-quantitative assessment of structural pathology using the Magnetic Resonance Imaging Osteoarthritis Knee Score (MOAKS), where scores range from 0 (no cartilage damage) to 3 (severe cartilage damage), with higher scores indicating greater pathology, across fourteen articular sub-regions.	Baseline, 6, and 36 months follow-up visits

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Endpoint: Biomarkers of Joint Tissue Remodeling	Circulating and synovial fluid markers of joint tissue remodeling (e.g., CTX-I, CTX-II, PRO-C2, C1M) will be measured using validated immunoassays with detection limits in the nanogram-per-milliliter (ng/mL) range.	Baseline, 6, and 36 months follow-up visits
Exploratory Endpoint: Inflammatory Cytokines	Plasma or serum concentrations of inflammatory cytokines and soluble mediators (e.g., TNF-α, G-CSF, IFN-γ, IL-6) will be determined using validated multiplex immunoassays with detection limits in the picogramm-per-milliliter (pg/mL) range.	Baseline, 6, and 36 months follow-up visits
Exploratory Endpoint: Cellular Biomarkers	Immune cell subpopulations in peripheral blood and synovial fluid are analyzed by standardized multiparameter flow cytometry for basic phenotyping of T cells, B cells and myeloid cell populations and reported either as absolute or relative cell count.	Baseline, 6, and 36 months follow-up visits

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2024
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: September 9, 2024
• First Submitted That Met QC Criteria: September 11, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): March 2, 2026
• Last Update Submitted That Met QC Criteria: February 27, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Osteoarthritis
• Other Study ID Numbers: PROTO-WP4; 101095635 (Other Grant/Funding Number: Horizon-Programm der EU)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No