A 2-year, European Multicentre Study to Describe, Validate, and Predict Phenotypes of Knee Osteoarthritis

NCT ID: NCT03883568

Last Updated: 2022-06-01

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 297 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-01-19
• Study Completion Date: 2021-12-01

Brief Summary

Rationale: Despite a large and growing disease burden in osteoarthritis (OA), many pharmaceutical companies have abandoned OA drug development. This is mainly due to the lack of appropriate outcome measures that can robustly identify patients that can benefit from a specific therapy. Different phenotypes of OA may benefit from different types of treatment. Therefore, novel markers to identify selected phenotypes of osteoarthritis may encourage drug development.

Objective: To prospectively describe in detail pre-identified progressing phenotypes of patients with knee OA by use of conventional and novel clinical, imaging, and biochemical (bio)markers, and to validate and refine a predictive model for these (and new) progressing phenotypes based on these markers.

Study design: APPROACH is an exploratory, European, five-centre, 2-year prospective follow-up, cohort study, with extensive measurements. In this study patients are treated according to regular care by their own physician with no study related treatment prescribed. Study related diagnostic and/or monitoring procedures are applied to the patients.

Study population: Patients with tibiofemoral knee osteoarthritis, according to the clinical ACR classification criteria, pre-identified based on demographic (e.g. age), clinical (e.g. Pain NRS) and tissue structure (e.g. radiographic joint space width) parameters.

Main study parameters/endpoints: Joint tissue structure based on radiographs, MRI, and biochemical (bio)markers as well as symptoms (pain, function) and quality of life by questionnaires.

Secondary parameters: A multitude of (novel and conventional) clinical, imaging, and biochemical parameters related to osteoarthritis.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The participants will not have any direct benefit from their participation in this study other than that their OA is maximally diagnosed and followed in detail for up to 2 years (screening, baseline, 6 months, 12 months, 24 months).

Detailed Description

Patients will stay in the hospital for 4-5 hours per visit (for screening about 30 min) for physical examination, blood draw, MRI scans, radiographs of knees and hands (only at baseline and 24 months), CT scan of the knee (only at baseline and 24 months), low radiation whole body CT scan (only at baseline and 24 months), HandScan (only at baseline and 24 months), motion analysis, and performance based tests. They will be asked to fill out questionnaires about knee, hand and hip osteoarthritis, and about general health and pain. The patient council in the consortium indicated that the load is acceptable. The patient council will be involved in the execution of the study. The assumed risk is minimal for an individual patient and minimal compared to the contribution to the development of knowledge of their disease. These risks include minimal events due to blood sampling itself (such as hematoma or localized bleeding), radiation exposure by radiographic imaging techniques (with a minimal increased healthcare risk), and exposure to MRI techniques (without known risks and without use of contrast agents).

Conditions

Knee Osteoarthritis

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

1. Informed consent obtained.

2. Ambulatory (able to walk unassisted)

3. At least 18 years of age

4. Capable of understanding the study

5. Capable of writing and reading in local language

6. Predominantly tibiofemoral knee osteoarthritis and satisfy the clinical classification criteria of the American College of Rheumatology (ACR): Knee pain and three of the following criteria: over 50 years age, less than 30 minutes of morning stiffness, crepitus on active motion, bony tenderness, bony enlargement, or no palpable warmth.

7. Highest probability to progress based on the algorithm based on the following parameters:

• Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire
• BMI (in recording height and weight)
• Pain NRS of the index knee at the moment of the screening visit
• Pain NRS of the index knee during the last week before the screening visit
• Age
• Gender
• KIDA parameters of the index knee, based on standardized weight-bearing (KIDA) radiograph, measured < 3 months (patients with a Joint Space Width (JSW) < 2 mm of the index knee will not be included)

Exclusion Criteria

8. Not being able to comply to the protocol

9. Participating in a trial with local therapeutic intervention for index knee OA (pharmaceutical or surgical) or systemic Disease Modifying OsteoArthritic Drugs (DMOADs) or potential DMOADs treatments for OA at the same time or within the past 6 months or anticipated in the forthcoming; participation in non-interventional registries or epidemiological studies is allowed.

10. Surgery of the index knee in the past 6 months (to avoid interferences with imaging)

11. Scheduled or expected surgery of the index knee in the next 2 years (to avoid interferences with imaging)

12. Pregnancy (child bearing woman) because of imaging (radiation and MRI, risks)

13. Predominantly patellar femoral knee OA (clinical judgment)

14. The following secondary osteoarthritis of the knee: clinically significant deformities of the lower limbs (varus >10°, valgus >10°), septic arthritis, inflammatory joint disease, gout, major chondrocalcinosis (pseudogout), Paget's disease of the bone, ochronosis, acromegaly, haemochromatosis, Wilson's disease, rheumatic symptoms due to malignancies, primary osteochondromatosis, osteonecrosis, osteochondritis dissecans, haemophilia

15. Generalized pain syndrome, for example fibromyalgia

16. Patients with contra indication to MRI or CT

17. Hip replacement or expected hip replacement within 6 months

18. Osteosynthesis material near the knee joint

19. Self-reported severe Intervertebral disc (IVD) degeneration or facet OA

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Nordic Bioscience A/S

INDUSTRY

Sponsor Role: collaborator

University of Surrey

OTHER

Sponsor Role: collaborator

Leiden University Medical Center

OTHER

Sponsor Role: collaborator

Complexo Hospitalario Universitario de A Coruña

OTHER

Sponsor Role: collaborator

Institut de Recherches Internationales Servier

OTHER

Sponsor Role: collaborator

Newcastle University

OTHER

Sponsor Role: collaborator

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: collaborator

Diakonhjemmet Hospital

OTHER

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: collaborator

F.P.J.G. Lafeber

OTHER

Sponsor Role: lead

Responsible Party

F.P.J.G. Lafeber

Professor, director of research

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Floris PJ Lafeber, PhD

Role: STUDY_DIRECTOR

UMC Utrecht

Locations

Saint-Antoine hospital, AP-HP

Paris, , France

Leiden University Medical Center

Leiden, , Netherlands

UMC Utrecht

Utrecht, , Netherlands

Diakonhjemmet hospital

Oslo, , Norway

SERGAS

A Coruña, , Spain

Countries

France; Netherlands; Norway; Spain

References

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Reference Type: DERIVED

PMID: 37179936 (View on PubMed)

Brett A, Bowes MA, Conaghan PG. Comparison of 3D quantitative osteoarthritis imaging biomarkers from paired CT and MR images: data from the IMI-APPROACH study. BMC Musculoskelet Disord. 2023 Jan 30;24(1):76. doi: 10.1186/s12891-023-06187-2.

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Reference Type: DERIVED

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Taylor J, Dekker S, Jurg D, Skandsen J, Grossman M, Marijnissen AK, Ladel C, Mobasheri A, Larkin J, Weinans H, Kanter-Schlifke I; APPROACH research consortium and APPROACH Principal Investigators. Making the patient voice heard in a research consortium: experiences from an EU project (IMI-APPROACH). Res Involv Engagem. 2021 May 10;7(1):24. doi: 10.1186/s40900-021-00267-0.

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Other Identifiers

APPROACH-OA-P01

Identifier Type: -

Identifier Source: org_study_id