None listed
Conditions
Brief summary
The aim of this study is to compare, using a randomised, placebo-controlled double-blind design over two years, the effect of an annual infusion of zoledronic acid to placebo on knee structural change assessed on MRI and knee pain in patients with knee osteoarthritis, significant knee pain and an MRI detected knee bone marrow lesion. We will recruit 264 subjects in Hobart, Melbourne, Sydney, and Adelaide. Eligible subjects will receive an annual identical intravenous infusion of zoledronic acid (5mg in normal saline) or placebo (normal saline), over two years. Outcome measures include cartilage loss over 24 months, knee pain at 3, 6, 12, 18, and 24 months, and bone marrow lesion size over 6 and 24 months.
Interventions
Annual IV infusion of 100ml of fluid containing zoledronic acid (5mg/100mL) for 2 years
Sponsors
Menzies Research Institute Tasmania, University of Tasmania
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1) Males and females with significant knee pain on most days (defined as a pain score >= 40 mm on a 100-mm visual analogue scale (VAS)). 2) Aged >= 50 years old. 3) Bone marrow lesions present on MRI. 4) Meeting the American College of Rheumatology (ACR) criteria for symptomatic knee osteoarthritis.
Exclusion criteria
1) Prior use of bisphosphonates, except according to the washout schedule: 2 years (if use >48 weeks) 1 year (if used >8 weeks but <48 weeks) 6 months (if used >2 weeks but <8 weeks) 2 months (if used <2 weeks) Any IV bisphosphonate within the prior 2 years 2) History of non-traumatic iritis or uveitis 3) Abnormal blood tests [serum calcium >2.75 mmol/L (11.0 mg/dL) or <2.00 mmol/L (8.0 mg/dL) or creatinine clearance < 35 ml/min] 4) Serum 25-hydroxyvitamin D concentrations <40 nmol/L 5) Use of any investigational drug(s) and/or devices within 30 days or 5 half-lives (whichever is longer) of the drug prior to randomisation 6) Prior diagnosis of cancer (metastatic cancer or cancer diagnosed < 2 years ago where treatment is still ongoing) 7) Poor dental fitness: A dental exam with appropriate preventative dentistry should be considered prior to treatment with bisphosphonates in patients with concomitant risk factors (e.g. cancer, chemotherapy, corticosteroids, poor hygiene) 8) Severe knee osteoarthritis (joint space narrowing (JSN)) on X-ray of Grade 3 using the Osteoarthritis Research Society International (OARSI) atlas) 9) Other forms of arthritis in which disease is active and concomitant medication is used (e.g. rheumatoid arthritis or other inflammatory arthritis) 10) Patients who have undergone arthroscopy or open surgery in the index knee in the last 12 months 11) Women who are pregnant or breast feeding 12) Patients who have had a corticosteroid injection in the last 3 months or a hyaluronic acid injection in the last 6 months in the index knee 13) Planned joint replacement surgery 14) Contraindication to MRI scanning (for example, implanted pacemaker, metal sutures, presence of shrapnel or iron filings in the eye, claustrophobia, knee too large for coil) 15) Inability to give informed consent
Outcome results
None listed