A Phase 3, Investigator-initiated, Randomized, Open-label Single-center Study of the Effect of Denosumab on the Prevention of Bone Mineral Density Loss After Renal Transplantation
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Percent Change in BMD at the Total Lumbar Spine From Baseline to Month 12
研究概览
简要总结
The primary objective of the study is to examine the effect of denosumab on lumbar spine bone mineral density (BMD) after one year of treatment in newly transplanted renal allograft recipients. Secondary endpoints include BMD changes at the total hip and the femoral neck, changes in body height, changes in bone mineral metabolism parameters, incidence of fractures, and allograft function at one year. Safety measurements include the occurrence of rejection episodes, infectious complications, graft loss and mortality.
- Trial with medicinal product
详细描述
Renal allograft recipients are at high risk to suffer a substantial loss of bone mineral density (BMD) within the first year after kidney transplantation. This loss of BMD correlates with an increased risk for the development of osteoporosis or worsening of pre-existing osteopenia/osteoporosis, heightening the risk for the subsequent occurrence of fractures. Renal allograft recipients are often treated with calcium and vitamin D preparations to prevent BMD loss. The addition of bisphosphonates can further improve BMD. However, bisphosphonates are potentially nephrotoxic and promote adynamic bone disease, and are therefore not regularly prescribed.
Receptor Activator of Nuclear factor- Kappa-B Ligand (RANKL) is a key molecule mediating development, activity, and survival of osteoclasts. Osteoporosis results in part from increased osteoclastic bone resorption, and therefore the inhibition of RANKL activity has become an obvious therapeutic strategy to prevent bone mineral density (BMD) loss and the development of osteoporosis.
The novel anti-osteoporotic drug denosumab (trade name Prolia®) is a fully human monoclonal antibody against RANKL. By inhibiting the development and the activity as well as reducing the survival of osteoclasts it decreases bone resorption and increases bone density.
The hypothesis of the present study is that denosumab has a beneficial effect on the loss of BMD in the first year after renal transplantation. The preservation of BMD is a surrogate parameter, generally predicting subsequent improvements in the occurrence rate of fractures. The hypothesis will be tested by studying the effect of denosumab on BMD in newly transplanted renal allograft recipients.
The purpose of the present trial is to study the effect of denosumab on BMD in kidney allograft recipients. The study participants will be treated for 1 year, receiving a total of 2 injections of the standard 60 mg dose at baseline and at 6 months.
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
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Denosumab
60 mg denosumab s.c. at baseline and after 6 months
干预措施: Denosumab (Prolia) (Drug)
结局指标
主要结局
Percent Change in BMD at the Total Lumbar Spine From Baseline to Month 12
时间窗: Baseline and month 12
The total lumbar spine BMD was measured via Dual Energy X-ray Absorptiometry (DXA) and was expressed in g/cm2 hydroxylapatite
次要结局
- Percent Change in BMD at the Total Hip From Baseline to Month 12(Baseline and month 12)
- Percent Change in BMD at the Femoral Neck From Baseline to Month 12(Baseline and month 12)
- Percent Change in BMD at the Total Lumbar Spine From Baseline to Month 6(Baseline and month 6)
- Percent Change in BMD at the Total Hip From Baseline to Month 6(Baseline and month 6)
- Percent Change in BMD at the Femoral Neck From Baseline to Month 6(Baseline and month 6)
- Beta-CTX at Baseline and Months 3, 6 and 12(baseline, month 3, month 6, and month 12)
- P1NP at Baseline and Months 3, 6 and 12(baseline, month 3, month 6, and month 12)
研究者
Rudolf Wuethrich
Professor and Director
University of Zurich