Exploring Factors Linked to Worsening Over Time in People With Early-stage Knee Osteoarthritis and Those With Prior Proven Acute Knee Injury.

NCT07833488 | Not Yet Recruiting

• 2 other identifiers: 26/LO/0569IRAS ID: 323431
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this observational, non-interventional cohort study is to identify tests or markers in blood or knee fluid, or any genetic risk factors that might contribute to worsening or improvement of knee osteoarthritis. Males and females aged ≥18 with early-stage knee osteoarthritis, prior proven acute knee injury, or degenerative meniscal tear will be recruited at Imperial College Healthcare NHS Trust. Participants with prior proven acute knee injury must be aged ≤ 50. A single knee per participant will be followed throughout the study; this will be referred to as ''affected knee'', identified at baseline. The study involves:

• From individuals recruited in-person: blood or buccal (cheek) swab and/or knee joint (synovial) fluid - this will be collected during routine NHS visit, if individuals undergo scheduled knee surgery or knee aspiration procedure (Knee aspiration is a procedure to remove excess fluid from the knee joint for diagnosis or treatment).
• From individuals recruited remotely: saliva sample.
• Clinical data collection at baseline:
• Clinical data collection at yearly remote visits, through years 1-5:
• Imaging data collection at baseline and at Year 2 or Year 3 follow-up visit:

Conditions

Knee Osteoarthritis

Keywords

post-traumatic knee osteoarthritis; genetics; synovial fluid; protein marker; knee injury; knee

Outcome Measures

Primary Outcomes (1)

• Knee injury and Osteoarthritis Outcome Score (KOOS)

  Collected via study questionnaires completed by participants. Knee Injury and Osteoarthritis Outcome Score (KOOS) is a knee-specific self-reported instrument, developed to assess participant's opinions about their knee and associated problems. The KOOS evaluates both short-term and long-term consequences of knee injury and osteoarthritis. It holds 42 items in 5 separately scored subscales: Pain, other Symptoms, Function in daily living , Function in Sport and Recreation, and knee-related Quality of Life. The KOOS is scored from 0 to 100, where higher scores indicate a better outcome, representing fewer symptoms and better knee-related quality of life.

  Baseline and 2 years

Secondary Outcomes (3)

• Tegner Activity Score (TAS)

  Baseline and minimum at 2 years/maximum 5 years

• Post enrolment surgical intervention data (arthroplasty)

  Years 1-5

• X-ray radiographs of the index knee

  Baseline and 2 years

Study Arms (2)

Individuals with early-stage knee osteoarthritis (or degenerative meniscal tear).

Males and females aged ≥18.

Individuals with prior proven acute knee injury.

Males and females must be aged ≤ 50.

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

Participants will be recruited across Imperial College Healthcare NHS Trust (ICHNT) through four primary pathways: 1. Elective Orthopaedic Lists: Patients scheduled for relevant procedures on elective orthopaedic surgical lists. 2. Outpatient Procedural Lists: Patients scheduled for joint drainage or intra-articular injections within musculoskeletal specialties, including rheumatology, sports and exercise medicine, and musculoskeletal radiology. 3. Participants from existing research cohorts, such as the Imperial College Healthcare Tissue Bank (ICHTB), i.e., i-Bank, who are eligible and have previously consented to be re-contacted for future studies. 4. Research Registries: Individuals identified via research registries and mailing lists, including the Imperial Joint Health: Understanding, Monitoring and Prevention (JUMP) Registry, the Northwest London Health Research Register, and the Imperial Health Knowledge Bank (IHKB).

You may qualify if:

• ALL participants must meet the following criteria:
• Male or female, aged ≥18 years of age AND at least one of the following (a-d):
• A definite diagnosis of knee osteoarthritis , evidenced by consistent knee symptoms and imaging findings, commensurate with non-advanced KL grade changes (KL 0-2 where an X-ray grade is available)
• A symptomatic degenerative meniscal tear with or without definite imaging findings suggesting knee osteoarthritis
• Probable early-stage symptomatic knee osteoarthritis without definite imaging changes, fulfilling NICE diagnostic criteria for osteoarthritis:
• Age 45 or over
• Activity-related knee pain.
• Either no morning stiffness or that lasts \<30 minutes
• A definite clinically significant acute knee injury at the age of 50 or younger at any stage in the past, evidenced by appropriate clinical history of a traumatic knee episode AND documented imaging or surgical confirmation of a relevant structural injury.
• Willing to provide at least one of the following samples: synovial fluid or blood (a salivary sample is an acceptable alternative for remote participants with a history of knee injury. This alternative also applies to existing participants from ICHTB/IHKB, for whom no prior DNA sample is currently banked)
• Understand English sufficiently to be able to read PIS, ICF and/or Participant Invitation Letter
• Provide an ICF, signed by the participant
• Be capable of complying with Protocol requirements, i.e. completing study questionnaire packs.

You may not qualify if:

• Known advanced radiographic changes of KOA on available imaging (KL grade 3-4 where available), or other commensurate findings, such as those present on MRI
• Knee joint replacement (uni-compartmental arthroplasty or total knee arthroplasty) of the index knee, prior to consent, or planned during current episode of care, or within next 12 months
• Other clinically significant knee pathology such as infection or malignancy affecting the index knee joint or surrounding bone (at any time)
• Surgery to the index knee in the last 3 months
• Any other systemic inflammatory disease (e.g. inflammatory bowel disease), systemic infection, or inflammatory arthritis (e.g. rheumatoid arthritis, psoriatic arthritis, gout)
• Systemic/intra-articular steroid use to index knee in the last 3 months
• Any use of immunosuppressive drugs or chemotherapy in the last 12 months
• Unwilling or unable to provide follow-up data for minimum 2 years and/or maximum 5 years
• Pregnancy, expecting to be pregnant, near the scheduled Year 2 or Year 3 X-ray visit.
• Other medical reason which would prevent participation, at the discretion of the investigator.

Sponsors & Collaborators

• Imperial College London: lead
• Arthritis UK: collaborator
• UK Research and Innovation: collaborator

Study Sites (1)

Centre for Inflammatory Disease, 9th Floor, Commonwealth Building, Imperial College London, Department of Immunology and Inflammation, Hammersmith Campus, Du Cane Road, London

London, W12 0NN, United Kingdom

Location

Related Publications (16)

• Perry T, Deng Y, Hulley P, et al. Deconvoluting synovial fluid molecular endotypes in knee osteoarthritis: primary results from the STEpUP OA Consortium. medRxiv; 2024. DOI: 10.1101/2024.06.05.24308485.

  BACKGROUND

• Osteoarthritis in over 16s: diagnosis and management. London: National Institute for Health and Care Excellence (NICE); 2022 Oct 19. Available from http://www.ncbi.nlm.nih.gov/books/NBK588843/

  PMID: 36745715 BACKGROUND

• Burn E, Murray DW, Hawker GA, Pinedo-Villanueva R, Prieto-Alhambra D. Lifetime risk of knee and hip replacement following a GP diagnosis of osteoarthritis: a real-world cohort study. Osteoarthritis Cartilage. 2019 Nov;27(11):1627-1635. doi: 10.1016/j.joca.2019.06.004. Epub 2019 Jun 17.

  PMID: 31220608 BACKGROUND

• Garriga C, Goff M, Paterson E, Hrusecka R, Hamid B, Alderson J, Leyland K, Honeyfield L, Greenshields L, Satchithananda K, Lim A, Arden NK, Judge A, Williams A, Vincent TL, Watt FE. Clinical and molecular associations with outcomes at 2 years after acute knee injury: a longitudinal study in the Knee Injury Cohort at the Kennedy (KICK). Lancet Rheumatol. 2021 Jun 24;3(9):e648-e658. doi: 10.1016/S2665-9913(21)00116-8. eCollection 2021 Sep.

  PMID: 34476411 BACKGROUND

• Kalsoum R, Minns Lowe CJ, Gilbert S, McCaskie AW, Snow M, Wright K, Bruce G, Mason DJ, Watt FE. A mixed-methods approach exploring acceptability and feasibility of trials designed to test drugs targeting prevention of post-traumatic osteoarthritis after knee injury. Bone Joint Res. 2024 Sep 19;13(9):513-524. doi: 10.1302/2046-3758.139.BJR-2024-0109.

  PMID: 39293808 BACKGROUND

• Hollis B, Chatzigeorgiou C, Southam L, Hatzikotoulas K, Kluzek S, Williams A; Genetics of Osteoarthritis Consortium; Zeggini E, Jostins-Dean L, Watt FE. Lifetime risk and genetic predisposition to post-traumatic OA of the knee in the UK Biobank. Osteoarthritis Cartilage. 2023 Oct;31(10):1377-1387. doi: 10.1016/j.joca.2023.05.012. Epub 2023 May 27.

  PMID: 37247657 BACKGROUND

• Watt FE, Paterson E, Freidin A, Kenny M, Judge A, Saklatvala J, Williams A, Vincent TL. Acute Molecular Changes in Synovial Fluid Following Human Knee Injury: Association With Early Clinical Outcomes. Arthritis Rheumatol. 2016 Sep;68(9):2129-40. doi: 10.1002/art.39677.

  PMID: 26991527 BACKGROUND

• Paskins Z, Farmer CE, Manning F, Andersson DA, Barlow T, Bishop FL, Brown CA, Clark A, Clark EM, Dulake D, Gulati M, Le Maitre CL, Jones RK, Loughlin J, Mason DJ, McCarron M, Millar NL, Pandit H, Peat G, Richardson SM, Salt EJ, Taylor EJ, Troeberg L, Wilcox RK, Wise E, Wilkinson C, Watt FE; Musculoskeletal Disorders Research Advisory Group Versus Arthritis. Research priorities to reduce the impact of musculoskeletal disorders: a priority setting exercise with the child health and nutrition research initiative method. Lancet Rheumatol. 2022 Jul 27;4(9):e635-e645. doi: 10.1016/S2665-9913(22)00136-9. eCollection 2022 Sep.

  PMID: 36275038 BACKGROUND

• Liu Q, Chu H, LaValley MP, Hunter DJ, Zhang H, Tao L, Zhan S, Lin J, Zhang Y. Prediction models for the risk of total knee replacement: development and validation using data from multicentre cohort studies. Lancet Rheumatol. 2022 Feb;4(2):e125-e134. doi: 10.1016/s2665-9913(21)00324-6. Epub 2022 Jan 5.

  PMID: 36177295 BACKGROUND

• Lo GH, Schneider E, Driban JB, Price LL, Hunter DJ, Eaton CB, Hochberg MC, Jackson RD, Kwoh CK, Nevitt MC, Lynch JA, McAlindon TE; OAI Investigators Group. Periarticular bone predicts knee osteoarthritis progression: Data from the Osteoarthritis Initiative. Semin Arthritis Rheum. 2018 Oct;48(2):155-161. doi: 10.1016/j.semarthrit.2018.01.008. Epub 2018 Jan 31.

  PMID: 29449014 BACKGROUND

• Collins NJ, Misra D, Felson DT, Crossley KM, Roos EM. Measures of knee function: International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form, Knee Injury and Osteoarthritis Outcome Score (KOOS), Knee Injury and Osteoarthritis Outcome Score Physical Function Short Form (KOOS-PS), Knee Outcome Survey Activities of Daily Living Scale (KOS-ADL), Lysholm Knee Scoring Scale, Oxford Knee Score (OKS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Activity Rating Scale (ARS), and Tegner Activity Score (TAS). Arthritis Care Res (Hoboken). 2011 Nov;63 Suppl 11(0 11):S208-28. doi: 10.1002/acr.20632. No abstract available.

  PMID: 22588746 BACKGROUND

• Roos EM, Lohmander LS. The Knee injury and Osteoarthritis Outcome Score (KOOS): from joint injury to osteoarthritis. Health Qual Life Outcomes. 2003 Nov 3;1:64. doi: 10.1186/1477-7525-1-64.

  PMID: 14613558 BACKGROUND

• Brown TD, Johnston RC, Saltzman CL, Marsh JL, Buckwalter JA. Posttraumatic osteoarthritis: a first estimate of incidence, prevalence, and burden of disease. J Orthop Trauma. 2006 Nov-Dec;20(10):739-44. doi: 10.1097/01.bot.0000246468.80635.ef.

  PMID: 17106388 BACKGROUND

• Lohmander LS, Englund PM, Dahl LL, Roos EM. The long-term consequence of anterior cruciate ligament and meniscus injuries: osteoarthritis. Am J Sports Med. 2007 Oct;35(10):1756-69. doi: 10.1177/0363546507307396. Epub 2007 Aug 29.

  PMID: 17761605 BACKGROUND

• Nicholls E, Thomas E, van der Windt DA, Croft PR, Peat G. Pain trajectory groups in persons with, or at high risk of, knee osteoarthritis: findings from the Knee Clinical Assessment Study and the Osteoarthritis Initiative. Osteoarthritis Cartilage. 2014 Dec;22(12):2041-50. doi: 10.1016/j.joca.2014.09.026. Epub 2014 Oct 8.

  PMID: 25305072 BACKGROUND

• Watt FE. Posttraumatic osteoarthritis: what have we learned to advance osteoarthritis? Curr Opin Rheumatol. 2021 Jan;33(1):74-83. doi: 10.1097/BOR.0000000000000760.

  PMID: 33186246 BACKGROUND

Related Links

• Imperial JUMP Registry

Biospecimen

Retention: SAMPLES WITH DNA

Samples with DNA: whole blood , saliva, buccal swab sample, synovial fluid. Samples without DNA: synovial fluid, plasma, serum.

MeSH Terms

Conditions

Osteoarthritis, Knee; Knee Injuries

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Leg Injuries; Wounds and Injuries

Study Officials

• Fiona Watt, Dr

  Imperial College London

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fiona Watt

CONTACT

+44 07858 367326; f.watt@imperial.ac.uk

Malgorzata Kochanska

CONTACT

+44 07858 367326; oaresearchgroup@imperial.ac.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2026
• First Posted: September 22, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): July 31, 2031
• Study Completion (Estimated): July 31, 2031
• Last Updated: September 28, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)