The Effect of REgulation of PArathyroId hoRmone in Patients With Chronic Kidney Disease to Investigate the Change in Bone Mineral Density (Biskjoldbruskkirtelhormon og knogletæthed Hos Patienter Med Kronisk Nyresygdom)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Difference in percent change in bone mineral density (BMD) between the treatment groups.
研究概览
简要总结
The prevalence of chronic kidney disease (CKD) in the adult population is estimated to 10%. CKD increases risk of bone fractures, cardiovascular disease and death. The main role of parathyroid hormone (PTH) is to regulate mineral metabolism, including the calcium and phosphate homeostasis. PTH increases as the kidney function declines, and at end stage kidney disease almost all patients have disturbances in the mineral metabolism. Decreasing bone mineral density is associated with risk of fracture, both in background population and in patients with CKD.
For decades, treatment with activated vitamin D, phosphate binders, and calcium supplements has been used for patients with chronic kidney disease and elevated parathyroid hormone, but treatment targets have varied greatly over the years, reflecting the lack of randomized clinical trials with clinical important end points.
The purpose of The REPAIR-CKD trial is to determine if treatment of hyperparathyroidism improves the bone mineral density in patients with chronic kidney disease.
During this trial it will also be evaluated if it is feasible to obtain a difference in PTH levels when targeting two different levels of PTH.
Further this trial will explore if a difference in PTH influences on arterial stiffness, muscle mass, muscle function, bone histology and health related quality of life.
详细描述
The prevalence of chronic kidney disease (CKD) is estimated to afflict 10 % of the adult population, and it is increasing world-wide. CKD is a devastating disease due to the risk of kidney failure and thereby the need for dialysis or transplantation, but also because the presence of CKD increases the risk of bone fracture, cardiovascular disease and mortality.
Parathyroid hormone (PTH) is a peptide hormone produced by the parathyroid glands(5). The main function of PTH is to regulate mineral metabolism, including the calcium and phosphate homeostasis. PTH increases as the kidney function declines, and at end stage kidney disease almost all patients have disturbances in the mineral metabolism. Treatment with activated vitamin D, phosphate binder and calcium supplementation has been used for more than 30 years to suppress hyperparathyroidism and keep calcium and phosphate within the normal range. Later calcimetics has been introduced as a treatment for secondary hyperparathyroidism.
The risk of bone fracture is increased in patients with CKD and the risk increases as the kidney function declines. A bone fracture leads to a direct burden on the individual. In addition, the risk of complications after a bone fracture is higher in the CKD population compared to the general population. A fracture also constitutes a significant cost for the society. The increased risk of fracture in patients with CKD is associated to the presence of hyperparathyroidism.
Bone mineral density (BMD) assessed by dual energy x-ray (DXA) scan is a highly used modality to diagnose osteoporosis and future fracture risk in the general population. Bone mineral density associates with the risk of future fracture in patients with CKD. In patients with CKD there is an association between decreasing eGFR and both low BMD and future fracture risk. It is unknown how elevated PTH associates with BMD and its changes at different stages of CKD, and it is unknown if treatment of hyperparathyroidism influence on BMD and fracture risk in patients with CKD.
The risk of cardiovascular mortality, coronary heart disease, heart failure, stroke and peripheral arterial disease increase as the kidney function declines. Elevated PTH associates with an increased risk of cardiovascular disease. However, hyperparathyroidism is tightly connected to the general disturbances in the mineral metabolism in CKD, i.e. hyperphosphatemia and elevated FGF-23, which associate with an increased risk of cardiovascular disease and mortality. Therefore, it is questioned if PTH is directly involved in the pathogenesis of cardiovascular disease, or if the increased risk of cardiovascular disease could be caused by other factors involved in the mineral metabolism. One way to approach precursors of vascular disease is measuring vascular stiffness with pulse wave velocity which is associated with cardiovascular outcomes in patients with CKD.
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
- Single (Investigator)
盲法说明
Investigators will be blinded to the primary endpoint (DEXA-scan and the analysis of this)
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥50 years of age at screening
- •CKD G4-5nonD (eGFR < 30 mL/min/1.73m2) based on local laboratory assessment of serum creatinine and eGFR estimated by the CKD-EPI formula)
- •Plasma PTH > upper normal limit of local laboratory reference range (> 8,5µmol/L) and/or treated with active vitamin D (Alphacalcidol) or calcimetics (Cinacalcet) initially
- •Written informed consent
排除标准
- •Patients who have received a kidney transplant
- •Patients receiving treatment with specific anti-osteoporosis medication (denosumab/bisphosphonates) (because of the profound effect on calcium/phosphate fluxes and BMD)
研究组 & 干预措施
PTH intensive target
Intensive parathyroid hormone target (within interval of lower and upper normal limits = 2,0 - 8,5 µmol/L). In the intensive PTH target group, treatment will be initiated as soon as the PTH rise above the upper limit of normal. Participants in this group will receive treatment to lower PTH level (activated vitamin D, phosphate binder, native vitamin D and calcimetics).
PTH will be measured as intact PTH with Atellica IM PTH assay at Herlev Hospital laboratory (normal range 2,0 - 8,5 µmol/L).
干预措施: Treat to target (Other)
PTH liberal target
Liberal parathyroid hormone target (< 5 x upper normal limit = 42,5 µmol/L). In the liberal PTH target group, treatment will not be initiated until PTH rise above five times the upper limit of normal. This is expected to be a small part of the participants.
The cut-off for the liberal PTH target (<5 x upper normal limit) was discussed in the national CKD-MBD group. It is chosen to allow the clinician initiate treatment if PTH reaches unusually high levels, no studies have focussed on PTH-targets before, consequently the cut-off is chosen as part of the pragmatic design.
干预措施: Treat to target (Other)
结局指标
主要结局
Difference in percent change in bone mineral density (BMD) between the treatment groups.
时间窗: From baseline to final follow-up at 18 months
Measured with DEXA-scan
次要结局
- Difference in follow-up BMD between treatment groups(From baseline to final follow-up at 18 months)
- Difference in follow-up arterial stiffness between the treatment groups(From baseline to final follow-up at 18 months)
- Difference in follow-up muscle mass between the treatment groups(From baseline to final follow-up at 18 months)
- Difference in follow-up hand grip strenght between the treatment groups(From baseline to final follow-up at 18 months)
- Difference in follow-up 10 meter walk test between the treatment groups(From baseline to final follow-up at 18 months)
- Difference in follow-up sit-to-stand test between the treatment groups(From baseline to final follow-up at 18 months)
- Differences in bone histology between the treatment groups(Labelling at baseline and repeated labelling and biopsy at 18 months)
- Differences in follow-up health-related quality of life between the treatment groups(From baseline to final follow-up at 18 months)
- Differences in number of spinal fractures between the treatment groups(From baseline to final follow-up at 18 months)
研究者
Freja Stæhr Hassager
Medical doctor
Herlev and Gentofte Hospital