Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03883568
Recruitment Status : Recruiting
First Posted : March 21, 2019
Last Update Posted : April 4, 2019
Sponsor:
Collaborators:
GlaxoSmithKline
Nordic Bioscience A/S
University of Surrey
Leiden University Medical Center
Complexo Hospitalario Universitario de A Coruña
Institut de Recherches Internationales Servier
Newcastle University
Merck KGaA, Darmstadt, Germany
Diakonhjemmet Hospital
Assistance Publique - Hôpitaux de Paris
Information provided by (Responsible Party):
F.P.J.G. Lafeber, UMC Utrecht

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).


Condition or disease
Knee Osteoarthritis

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).

Layout table for study information
Study Type : Observational
Estimated Enrollment : 300 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: A 2-year Multicentre, EU, Exploratory Study Without Therapeutic Benefit in Patients With Knee Osteoarthritis to Describe, Validate, and Predict Phenotypes of Knee Osteoarthritis by Use of Clinical, Imaging, and Biochemical (Bio)Markers.
Actual Study Start Date : January 19, 2018
Estimated Primary Completion Date : December 30, 2020
Estimated Study Completion Date : June 30, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Osteoarthritis




Primary Outcome Measures :
  1. OA structural progression of the index knee [ Time Frame: over two years ]
    radiographic joint space width in mm

  2. OA pain progression of the index knee [ Time Frame: over two years ]
    increase in points in Knee Osteoarthritis Outcome Score for pain (0-100; 0 worst, 100 best condition)


Secondary Outcome Measures :
  1. OA progression of the index knee [ Time Frame: over two years ]
    structural progression (e.g. cartilage volume on MRI in mm3)

  2. OA progression [ Time Frame: over two years ]
    structural progression (biochemical markers in units/ml in blood and urine)


Biospecimen Retention:   Samples With DNA
serum, plasma, blood DNA, blood RNA, urine


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
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.
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03883568


Contacts
Layout table for location contacts
Contact: Anne Karien Marijnissen, PhD 0031 887550459 a.c.a.marijnissen@umcutrecht.nl

Locations
Layout table for location information
France
Saint-Antoine hospital, AP-HP Not yet recruiting
Paris, France
Contact: F. Berenbaum, MD, PhD         
Netherlands
Leiden University Medical Center Recruiting
Leiden, Netherlands
Contact: G. Kloppenburg, MD, PhD         
UMC Utrecht Recruiting
Utrecht, Netherlands, 3584 CX
Contact: Anne Karien Marijnissen, PhD    0031 88 7550459    a.c.a.marijnissen@umcutrecht.nl   
Norway
Diakonhjemmet hospital Recruiting
Oslo, Norway
Contact: I Haugen, MD, PhD         
Spain
SERGAS Recruiting
A Coruña, Spain
Contact: F. Blanco, MD, PhD         
Sponsors and Collaborators
F.P.J.G. Lafeber
GlaxoSmithKline
Nordic Bioscience A/S
University of Surrey
Leiden University Medical Center
Complexo Hospitalario Universitario de A Coruña
Institut de Recherches Internationales Servier
Newcastle University
Merck KGaA, Darmstadt, Germany
Diakonhjemmet Hospital
Assistance Publique - Hôpitaux de Paris
Investigators
Layout table for investigator information
Study Director: Floris PJ Lafeber, PhD UMC Utrecht
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: F.P.J.G. Lafeber, Professor, director of research, UMC Utrecht
ClinicalTrials.gov Identifier: NCT03883568    
Other Study ID Numbers: APPROACH-OA-P01
First Posted: March 21, 2019    Key Record Dates
Last Update Posted: April 4, 2019
Last Verified: April 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by F.P.J.G. Lafeber, UMC Utrecht:
phenotypes
(bio)markers
Additional relevant MeSH terms:
Layout table for MeSH terms
Osteoarthritis
Osteoarthritis, Knee
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases