A Randomized Placebo Controlled Trial Testing The Effect of Zoledronic Acid on Hip Osteoarthritis
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Mean change in joint pain by VAS (Visual analogue pain scale from 1-10) from baseline to 12 months follow up, in the intervention group compared to the placebo group
研究概览
简要总结
Hip Osteoarthritis (OA) is one of the most common diseases affecting the ageing population. No specific and safe treatment slowing the development of hip OA as reflected in reduced joint space narrowing has been developed so far. Implantation of hip prosthesis has been a great success, but is expensive and puts a great financial pressure on hospitals and national healthcare programs. It also poses risks of serious complications. Current non-surgical treatment options focus on pain management and physiotherapy.
Bisphosphonates have been shown to exert multiple beneficial effects in OA. Animal studies have demonstrated that bisphosphonates protect against subchondral bone degradation and preserve articular cartilage in mice and rats with OA.
In this study 70 participants will be treated with either Zoledronic Acid (a potent Bisphosphonate) or Placebo (Saltwater). Allocation will be random and both parties are blinded. The investigators hypothesis is that participants treated with Zoledronic acid will have less pain, and better function after 12 months. The results will be tested with functional and pain scores, and functional tests. The study team will also measure the effects on disease related quality of life, bone quality measurements and the effect on bone marrow lesions on MRI (magnetic resonance imaging) and histological examination
详细描述
Background Hip Osteoarthritis (OA) is one of the most common diseases affecting the ageing population. No specific and safe treatment slowing the development of hip OA as reflected in reduced joint space narrowing has been developed so far. Implantation of hip prosthesis has been a great success, but is expensive and puts a great financial pressure on hospitals and national healthcare programs. It also poses risks of serious complications. Current non-surgical treatment options focus on pain management and physiotherapy.
Bisphosphonates have been shown to exert multiple beneficial effects in OA, not only through effects on subchondral bone, but also through chondroprotection and possibly by inhibiting synovitis. Animal studies have demonstrated that bisphosphonates protect against subchondral bone degradation and preserve articular cartilage in mice and rats with OA. Efforts to further improve subchondral bone using a combination of zoledronic acid (ZA) and parathyroid hormone (PTH), was, however, shown to be ineffective.
Rationale for study Effects of bisphosphonates in OA
Bisphosphonates may target Pain and OA development by several different mechanisms:
Anti-osteoclastic action:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
The treatment and placebo is administered through an infusion. Both will be administered in an identical infusion bag and are colorless. The mixing is performed by the same person who randomizes, less than 24 hours before administration. The bags are then put in a refrigerator and picked up later by a study nurse for administration. There is no "personal contact".
入排标准
- 年龄范围
- 50 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 50-80
- •Continuous worsening of hip pain with an onset of minimum 3 months
- •Hip Pain intensity >40mm on a visual analogue scale (VAS) ranging from 0 (no pain) to 100mm (maximal pain) during weight bearing for the last 7 days
- •HHS < 65 (Harris Hip Score)
- •Hip OA fulfilling the ACR (American College of Rheumatology) criteria [33]
- •Hip MRI scan showing large (>1 cm diameter) Bone Marrow lesions (BMLs)
- •Willing and able to consent and comply with the study protocol
排除标准
- •eGFR (estimated glomerular filtration rate) < 35 ml/min or hypocalcemia
- •Exposure to any treatment affecting bone other than Ca+D ( bisphosphonates, Denosumab teriparatide or continuous treatment of prednisolone)
- •Diseases affecting bone and joints (i.e inflammatory joint diseases, osteonecrosis with segmental collapse and deformation, primary bone cancer or known skeletal metastases)
- •Severe vitamin D deficiency (S-25(OH)D < 25 nmol/l) has to be supplemented with Ca+D before zoledronic acid infusion
- •Ipsilateral knee prosthesis
- •Contralateral hip prosthesis
- •Women of child bearing potential (WOCBP). Female participants must be in a postmenopausal state or permanent sterile.
- •Hypersensitivity or previous allergic reaction to ZA or other bisphosphonates.
- •Hypersensitivity or previous allergic reaction to Calcigran Forte (a calcium and vitamine D supplement) or Prednisolone
研究组 & 干预措施
Treatment Group
Participants receiving active treatment with two infusions of Zoledronic Acid 5 mg with 3 months interval mixed in 100 ml 0.9% saline
干预措施: Zoledronic Acid (Drug)
Placebo Group
Participants receiving Placebo with two infusions of 100 ml 0.9% saline with 3 months interval.
干预措施: Saline 0.9% (Drug)
结局指标
主要结局
Mean change in joint pain by VAS (Visual analogue pain scale from 1-10) from baseline to 12 months follow up, in the intervention group compared to the placebo group
时间窗: Baseline and 12 months
Pain during weight bearing measured with Visual Analogue Pain Scale
次要结局
- Mean change in joint pain by VAS from baseline to 3 and 6 months follow up, in the intervention group compared to the placebo group(baseline, 3 and 6 months)
- Mean change in function and activity score (HOOS) from baseline to 3, 6 and 12 months follow up, in the intervention group compared to the placebo group(baseline, 3, 6 and 12 months)
- Mean change in function and activity score (HHS) from baseline to 12 months follow up, in the intervention group compared to the placebo group(12 months)
- Mean change in 40mWT (40 meter walking test measured in seconds) from baseline to 3, 6 and 12 months follow up, in intervention group compared to placebo group(baseline, 3, 6 and 12 months)
- Mean change in SCT (Stair climb test measured in seconds) from baseline to 3, 6 and 12 months follow up, in intervention group compared to placebo group(baseline, 3, 6 and 12 months)
- Mean change in 30CST (Chair stand test, measured by number of repetitions in 30 seconds) from baseline to 3, 6 and 12 months follow up, in intervention group compared to placebo group(baseline, 3, 6 and 12 months)
- Change in mean number of doses of Paracetamol, NSAID and/or opiates per week in each group during the last month compared to baseline at 12 months follow up(baseline, 3, 6 and 12 months)
- Number of AE/SAE (adverse events and serious adverse events) and AR/SAR/SUSAR (adverse/serious adverse and suspected unexpected serious adverse reactions) in the intervention group compared to placebo group 12 months after first infusion.(baseline and 12 months)
- Mean change in QoL (EQ-5D) from baseline to 3, 6 and 12 months follow up, in the intervention group compared to the placebo group(baseline, 3, 6 and 12 months)
研究者
Morten Halkjær Iversen
Principal investigator
Martina Hansen's Hospital