The Effect of Denosumab on Pain and Bone Marrow Lesions in Symptomatic Knee Osteo-arthritis : A Randomised Double Blind Placebo Controlled Clinical Trial

Phase 1

• Conditions: Knee osteoarthritis; MedDRA version: 20.0Level: LLTClassification code 10023476Term: Knee osteoarthritisSystem Organ Class: 100000004859; Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

• Registration Number: EUCTR2016-000754-35-GB
• Lead Sponsor: The University of Manchester

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-05-08
• Last Update Posted: 5 January 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 167

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 11 on the primary symptom outcome of the trial, knee pain on a numerical rating scale (NRS Last week))
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

For those with bilateral symptomatic knee OA, we will select their more symptomatic knee for our primary outcome and will obtain the MRI's on this knee. If knees are equally symptomatic, we will study the one with the more severe radiographic changes (more likely to have BML's) and if both symptoms and radiographic changes are equivalent, we will choose the dominant knee.

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 67
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

Exclusion Criteria

1.History of septic arthritis, inflammatory arthritis or gout
2.Vitamin D level of < 50 nmol/l
3.Abnormal liver function (ALT or AST > twice upper limit of normal) or elevated total bilirubin > 1.5 x ULN
4.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
5.History of malignancy in the past 5 years (other than basal cell carcinoma)
6.History of any solid organ or bone marrow transplant
7.History of alcohol abuse within previous 12 months
8.Known hypersensitivity to Latex
9.Hereditary problems of fructose intolerance
10.Non-healed dental / oral surgery
11.History of cellulitis of the lower limb, osteonecrosis of the jaw or atypical femoral fractures
12.History of invasive dental surgery in previous 6 months
13.Invasive dental work planned in the 6 months
14.Current anorexia nervosa, suspected bulimia (by history or physical examination) or obvious malnutrition
15.Current or recent (within 1 year of enrolment) inflammatory bowel disease or malabsorption syndrome.
16.Hypo or hyperparathyroidism
17.Hypocalcemia (Calcium < LLN) / hypercalcemia (Ca > Upper Limit of Normal [ULN])
18.Osteoporosis on bone active therapy
19.Osteomalacia
20.Other bone diseases which may affect bone metabolism (osteopetrosis / osteogenesis imperfecta)
21.Known intolerance to calcium supplements
22.Intra-articular therapy in the knee within the previous 3 months
23.Prior antiresorptive therapy with bisphosphonates in the last year (oral therapy) or 3 years (IV therapy)
24.Prior treatment in the last year with strontium ranelate / HRT / raloxifene / testosterone
25.Previous knee surgery (including cartilage surgery) or arthroscopy within 6 months on the affected knee
26.Planned knee or hip surgery in the next 6 months
27.Currently having physiotherapy for knee OA
28.Women of childbearing potential currently pregnant or planning pregnancy or breast feeding
29.Women of childbearing potential and refusal to use 2 highly effective forms of contraception and to continue until 5 months following intervention
30.Concurrent life threatening illness or any other condition that in the opinion of the investigator would compromise participants safety or data integrity
31.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, cardiac or neural pacemakers, hydrocephalus shunts, or certain types of intrauterine-device. Also trial knee circumference must not be >55cm or weight >125kg as these exceed the maximum MRI limits
32.Currently enrolled in or has not yet completed at least 1 month since ending other investigational device or drug trial(s), or potential participant is receiving other investigational agent(s)
33.Pain from sites outside the knee that are significantly more troublesome to the potential participant than knee pain and which significantly interferes with the ability of the potential participant to assess their knee pain.
34.Unable to take in, understand or retain the information provided regarding the trial procedures.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified