Identification of Biochemical and Biomechanical Markers for Cartilage Degeneration in the Knee Joint (IBBM-CKJ)

NCT02555514 | Unknown

• 1 other identifier: IBBM-CKJ
• Study Type: observational
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

The association between varus malalignment and dynamic knee loading / adduction moment and progression of knee joint cartilage degeneration in the lateral compartment is unclear and has not been studied in detail before. There is a need to identify relevant parameters explaining this cause-effect relationship. It is the purpose of the study to correlate load changes in knee joints with biomechanical and biochemical alterations in cartilage to understand the underlying mechanism of load induced cartilage degeneration in patients. This study will therefore include patients with different stages of knee OA with various malalignments. Moreover, analyzing changes in cartilage morphology, radiography and MRI and correlate those findings with alterations in biochemical parameters in cartilage, serum, urine and synovial fluid will allow us to identify novel biomarkers for the onset and progression of joint cartilage degeneration in varus malaligned knees. The following hypotheses will be tested:

1. 1.Knee joint cartilage degeneration progresses from medial to lateral in varus-aligned knees.
2. 2.External knee adduction moments in patients with isolated medial OA are higher when compared with patients with OA of the medial and lateral compartment.
3. 3.Morphological and mechanical properties of cartilage show different stages of degeneration when comparing the mechanically stronger loaded medial with the lateral compartment of the knee.
4. 4.Histological and biochemical analysis of the cartilage indicate different stages of degeneration when comparing the mechanically loaded medial with the lesser loaded lateral compartment of the knee.
5. 5.Synovial fluid analysis, as well as serum biomarkers of cartilage metabolism demonstrate cartilage degeneration and are related to biomechanical determinants of OA in the knee.
6. 6.Novel biomarkers (ECM, miRNA, cytokines, mitochondria related, mechanical determinants) for varus-aligned knees can be identified.

Conditions

Osteoarthritis

Outcome Measures

Primary Outcomes (1)

• measurement of Knee joint cartilage degeneration progresses from medial to lateral in varus-aligned knees in mm .

  The association between varus malalignment and dynamic knee loading / adduction moment and progression of knee joint cartilage degeneration in the lateral compartment is unclear and has not been studied in detail before. There is a need to identify relevant parameters explaining this cause-effect relationship. It is the purpose of the study to correlate load changes in knee joints with biomechanical and biochemical alterations in cartilage to understand the underlying mechanism of load induced cartilage degeneration in patients. This study will therefore include patients with different stages of knee OA with various malalignments. Moreover, analyzing changes in cartilage morphology, radiography and MRI and correlate those findings with alterations in biochemical parameters in cartilage, serum, urine and synovial fluid will allow us to identify novel biomarkers for the onset and progression of joint cartilage degeneration in varus malaligned knees.

  Change from Baseline 12 month

Study Arms (1)

Knee Osteoarthritis

The study population consists of 100 enrolled patients with different stages of knee OA and varus malalignment \>4° with respect to the mechanical loading axis of the lower extremity. A minimum of 40 patients are to be included per year, so that the study period will be planned from January 1st, 2015 to June 30th, 2017. Preliminary results will be reviewed by the end of every year and intermediate reports will be generated by the sub-study-groups

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

End stage medial, bi- or tricompartimental OA with indication to total knee replacement with failure of conservative treatment

You may qualify if:

• End stage medial, bi- or tricompartimental OA with indication to total knee replacement with failure of conservative treatment
• No more than mild symptoms of other joints in the lower limbs (VAS≤ 4)
• Age \> 18 years
• BMI \< 35
• Written informed consent must be obtained from all patients prior to any study-related procedure.

You may not qualify if:

• BMI ≥ 35
• Post-infectious condition of the affected knee
• Valgus- or neutral lower limb axis
• Pacemaker or any other medical condition that does not allow MRI scans
• Systemic arthritic conditions
• Previous surgery of lower extremities and/or low back within the last 6 months
• Musculoskeletal or neurological condition severely affecting lower limb function
• Contraindications to MRI
• Not able to walk independently without a walking aid
• Additional infection

Sponsors & Collaborators

• Dr. Jan Siewe: lead

Biospecimen

Retention: SAMPLES WITH DNA

In order to investigate cartilage degeneration/turnover (COMP, collagen II, GAGs), miRNA and cytokine profiles 4 blood draws will be carried out

MeSH Terms

Conditions

Osteoarthritis

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Central Study Contacts

Johannes Oppermannn, Dr. med.

CONTACT

+49-221-478-87294; johannes.oppermann@uk-koeln.de

Jens Dargel, Dr.med.

CONTACT

+49-221-478-87294; jens.dargel@uk-koeln.de

Study Design

• Study Type: observational
• Observational Model: CASE CROSSOVER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Dr.med.

Study Record Dates

• First Submitted: September 15, 2015
• First Posted: September 21, 2015
• Study Start: October 1, 2015
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: September 21, 2015

Record last verified: 2015-09