Effects of Cholecalciferol on Osteoprotegerin Levels and Other Clinical Outcomes in Chronic Kidney Disease Patients on Peritoneal Dialysis: a Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 58
- 试验地点
- 1
- 主要终点
- Relative reduction in serum osteoprotegerin (OPG) levels assessed by ELISA (in pg/mL) between study inclusion, and the 16-week intervention period.
研究概览
简要总结
Aim: To investigate whether cholecalciferol (4800 U/daily) or placebo for 16 weeks reduces proteins levels associated with vascular calcification (osteoprotegerin, osteopontin, osteocalcin) in patients treated with peritoneal dialysis and 25(OH) vitamin D deficiency.
详细描述
Patients with chronic kidney disease on peritoneal dialysis have very low 25-(OH) vitamin D levels. Vitamin D deficiency may be involved in generalized atherosclerosis, vascular calcification and cardiovascular mortality. Among others, Osteoprotegerin (OPG) has been implicated in the pathogenesis leading up vessel calcification in this patients. Furthermore, very low levels of 25-(OH) vitamin D in peritoneal dialysis patients are associated with increased levels of OPG and high values of vascular calcification scores in x-rays.
It is unknown whether cholecalciferol supplementation in patients on peritoneal dialysis with low levels of 25-(OH) vitamin D could change the proteins associated with vascular calcification.
The objective is to conduct a randomized, double-blind, placebo-controlled study focusing on the impact of Cholecalciferol substitution in 25-OH vitamin D deficient peritoneal dialysis patients on circulating OPG and other osteogenic biomarkers levels during 16 weeks of intervention.
Moreover, the impact of cholecalciferol on serum calcium and phosphorus levels, Kidney Disease Quality of Life Short Form, and ultrasound characteristics of carotid arterial will be performed during the first four weeks after inclusion, and after 28 weeks postintervention.
Peritoneal dialysis patients found to have 25-(OH) vitamin D levels <20 ng/ml will be included and will be randomized to receive either oral cholecalciferol therapy or placebo. Cholecalciferol will be administered at a daily dose of 4800 IU over a time period of 16 weeks.
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)
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Peritoneal dialysis treatment for at least 3 months.
- •Concentrations of 25-oh vitamin D <20 ng / mL
- •Corrected calcium <10.5 mg / dL
- •Serum phosphorus <7.0 mg / dL
- •Intact parathyroid hormone > 50 pg / mL and <1500 pg/mL
排除标准
- •Active participation in another protocol.
- •Vitamin D deficiency due to a hereditary disease or liver disease.
- •Use of cholecalciferol ≥ 2000 IU per day within 6 months prior
- •New prescription of calcitriol or paricalcitol at any dose within three months prior to the intervention (The subjects may be taking calcitriol or paricalcitol only if these drugs are taken at least three months before and no substantial changes in dosage have been made).
- •Use of bisphosphonates.
- •Treatment with anticonvulsants or other drugs that affect the metabolism of vitamin D.
- •Pregnancy and lactation.
- •Active cancer or other active inflammatory disease.
- •HIV or AIDS
研究组 & 干预措施
Cholecalciferol
A capsule of pulverized cholecalciferol 4800 U will be administered once a day for 16 weeks. At serum calcium levels > 10.5 mg/dL (2.65 mmol/l) and/or at serum phosphorus levels > 7 mg/dL (2.26 mmol/L) capsule administration will be discontinued and restarted one month after when serum calcium levels or phosphorus levels declined to < 10.6 mg/dL and/or <7.1 mg/dL respectively.
干预措施: Cholecalciferol (Drug)
Placebo
An oral placebo capsule matching Cholecalciferol in terms of appearance, smell and taste will be administered once a day for 16 weeks. At serum calcium levels > 10.5 mg/dL (2.65 mmol/l) and/or at serum phosphorus levels > 7 mg/dL (2.26 mmol/L) capsule administration will be discontinued and restarted one month after when serum calcium levels or phosphorus levels declined to < 10.6 mg/dL and/or <7.1 mg/dL respectively.
干预措施: Placebo (Drug)
结局指标
主要结局
Relative reduction in serum osteoprotegerin (OPG) levels assessed by ELISA (in pg/mL) between study inclusion, and the 16-week intervention period.
时间窗: 16 weeks
The concentrations of OPG will be assessed using ELISA (Austin, Texas, USA) at inclusion and after 16 weeks of treatment with cholecalciferol or placebo.Minimum detectable concentrations for OPG are 1.9 pg/mL; intra and inter-assay coefficients of variability are 5% and 11% for OPG.
次要结局
- Relative reduction in circulating osteocalcin (OCN) levels (in pg/mL)(16 weeks)
- Relative reduction in circulating intact fibroblast growth factor 23 (FGF23) levels (in pg/mL)(16 weeks)
- Relative reduction in circulating osteopontin (OPN) levels (in pg/mL)(16 weeks)
- Relative reduction in intima-media thickness measurements in the carotid artery. Ultrasound examination will be performed at study inclusion, at 16 weeks after inclusion, and up to 52 weeks post inclusion.(52 weeks)
- Number of participants with courses of corrected calcium (>10.5 mg/dL) and phosphorus (>7 mg/dL) levels(16 weeks)
研究者
Juan C Ramirez-Sandoval
MD
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran