Osteoarthritis of the knee Musculoskeletal Diseases Musculoskeletal disorders
Conditions
Interventions
Prior to the study, potential participants are screened for eligibility with a knee x-ray, blood test, and a MRI scan to assess for Bone Marrow Lesions (BML). Those who meet the eligibility criteria,
Sponsors
The University of Manchester
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current participant inclusion criteria as of 02/10/2019: 1. Age 40 years and over. 2. Ambulatory (not wheel chair bound), and able and willing to comply with the intervention and follow up. 3. Significant knee pain (have at least a score of 3 out of 10 on the primary symptom outcome of the trial, knee pain on a numerical rating scale (NRS Last week =3) 4. Evidence of significant OA on, x-ray – Kellgren Lawrence grade 2 or 3. Participants can have Kellgren and Lawrence grade 2 or 3 in any knee compartment. 5. Evidence of BMLs in index knee on magnetic resonance scanning (MRI) 6. Written informed consent Previous participant inclusion criteria: 1. Age 50 years and over 2. Ambulatory (not wheel chair bound), and able and willing to comply with the intervention and follow up 3. Significant knee pain (have at least a score of 4 out of 10 on the primary symptom outcome of the trial, knee pain on a numerical rating scale (NRS Last week =4) 4. Evidence of significant OA on, x-ray – Kellgren Lawrence grade 2 or 3. Participants can have Kellgren and Lawrence grade 2 or 3 in any knee compartment. 5. Evidence of BMLs in index knee on magnetic resonance scanning (MRI) 6. Written informed consent
Exclusion criteria
Exclusion criteria: Current participant exclusion criteria as of 02/10/2019: 1. History of septic arthritis affecting the index knee 2. History of inflammatory arthritis 3. Current treatment for gout and/or acute attack of gout within the previous 5 years 4. GFR twice upper limit of normal) or elevated total bilirubin > 1.5 x ULN 7. Potential participants with a positive Hepatitis B surface antigen (HBsAg) or hepatitis C test result or a history of immune-deficiency diseases, including a positive HIV test result 8. History of malignancy in the past 5 years (other than basal cell carcinoma) 9. History of any solid organ or bone marrow transplant 10. History of alcohol abuse within previous 12 months 11. Known hypersensitivity to Latex 12. Hereditary problems of fructose intolerance 13. Non-healed dental / oral surgery 14. History of cellulitis of the lower limb within the last 5 years, osteonecrosis of the jaw, osteonecrosis of the external auditory meatus or atypical femoral fracture 15. Unhealed open soft tissue lesions in the mouth 16. History of invasive dental surgery in previous 6 months and/or invasive dental work planned in the next 6 months 17. Current anorexia nervosa, suspected bulimia (by history or physical examination) or obvious malnutrition 18. Active inflammatory bowel disease or current or recent malabsorption syndrome. 19. Hypo or hyperparathyroidism 20. Hypocalcemia (Calcium Upper Limit of Normal [ULN]) 21. Osteoporosis on bone active therapy 22. Current or recent Osteomalacia (within the last 5 years) or other bone diseases which may affect bone metabolism (osteopetrosis / osteogenesis imperfecta) 23. Suspected knee fracture 24. Intra-articular therapy in the knee within the previous 3 months 25. Prior antiresorptive therapy with bisphosphonates in the last year (oral therapy) or 3 years (IV therapy) 26. Prior treatment in the last year with strontium ranelate / HRT / raloxifene / testosterone 27. Previous knee surgery (including cartilage surgery) or arthroscopy within 6 months on the affected knee 28. Planned knee or hip surgery in the next 6 months 29. Currently having physiotherapy for knee OA 30. Women of childbearing potential currently pregnant or planning pregnancy or breast feeding 31. Women of childbearing potential and refusal to use at least one highly effective form of contraception (methods that can achieve a failure rate of less than 1% per year when used consistently and correctly) and to continue until 5 months following intervention. 32. Concurrent life threatening illness or any other condition that in the opinion of the investigator would compromise participants safety or data integrity 33. Contraindication to MRI such as implants which prohibit safe use of MRI scan including cochlear implants / metal objects in the body including certain joint prosthesis, cardia
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Total area of bone marrow lesions (assessed on MRI) at six months. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Knee pain using an 11 point (0–10) numerical rating scale (NRS) of knee pain intensity, at baseline, three, and six months. The change in knee pain using a NRS scale is the primary outcome recommended by IMMPACT (http://immpact.org/) 2. Knee pain on nominated activity using an 11 point (0-10) numerical rating scale (NRSNA) at three and six months 3. Knee symptoms assessed using KOOS at three and six months 4. Quality of life assessed using EuroQOL & SF12 at three and six months 5. Adverse events are assessed from data collected at each study visit 6. Bone marrow lesions (BML) volume measured on MRI at baseline and six months | — |
Countries
England, United Kingdom
Contacts
Public ContactGillian Armitt
Outcome results
None listed