Prospective Double Blind Multicentre Randomized Trial of Vitamine D Estimating the Profit of a Treatment by Vitamin D3 at the Dose of 100000 UI by Comparison With a Treatment in the Dose of 12 000 UI at Renal Transplanted Patients
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 538
- 试验地点
- 1
- 主要终点
- De novo diabetes mellitus
研究概览
简要总结
It has been proposed that the intake of high dose of cholecalciferol may have beneficial non classical effects (beside bone health). This could include the reduction of type 2 diabetes mellitus, cardiovascular diseases, cancers, autoimmune and infectious diseases. These pleiotropic effects are mostly documented by observational and experimental studies or small intervention trials. In renal transplant recipients, vitamin D insufficiency, defined as circulating 25(OH)vitamin D (25OHD) less than 30 ng/mL, is a frequent finding and this population is at risk of the previously cited complications.The primary purpose of this study is to compare the effects of high dose vs. low dose of cholecalciferol on a composite endpoint consisting in de novo diabetes mellitus, cardiovascular diseases, de novo cancer and patient death.Renal transplant recipients between 12 and 48 months after transplantation will be randomized to blindly receive either high or low dose of cholecalciferol with a follow-up of 2 years.
详细描述
Rationale :
Vitamin D cannot be considered any more as only necessary to prevent rickets or osteomalacia. Calcitriol produced in the kidney is known to have classical endocrine PHOSPHOCALCIC properties. More recently, vitamin D has been shown to play an important role in reducing the risk of many chronic diseases including type 2 diabetes mellitus, cardiovascular diseases, cancers, autoimmune and infectious diseases. These effects may be secondary to local production of calcitriol and to its autocrine and paracrine actions on cellular proliferation and differentiation, apoptosis, insulin and renin secretion, interleukin and bactericidal proteins production. These pleiotropic effects are mostly documented by observational and experimental studies or small intervention trials that most often evaluated intermediate parameters. In renal transplant recipients, vitamin D insufficiency (circulating 25OHD<30 ng/mL or 75 nmol/L) , is a frequent finding with more than 80% of patients displaying this profile.
Objective:
Primary objective: compare the effects of high dose vs. low dose of cholecalciferol on a composite endpoint including
- De novo diabetes mellitus (fasting glycemia > 7 MMOLES/l or glycemia > 11 MMOLES/l)
- Cardiovascular complications (acute coronary heart disease, acute heart failure, lower-extremity arterial disease, cerebrovascular disease).
- De novo cancer,
- Patient death.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Renal transplant recipients between 12 and 48 months after transplantation with a stable renal function during the past 3 months.
- •Vitamine D insufficiency defined as a concentration of 25OHD lower than 30 ng/ml.
- •Patient between 18 and 75 years old
- •Patient capable of understanding the advantages and the risks of the study.
- •Affiliated with social security health insurance
- •Written informed consent
排除标准
- •Calcaemia > 2,7 mmol/l
- •Phosphataemia > 1,5 mmol/l
- •Serum creatinine > 250 µmol/l
- •Treatment by an active form of the vitamin D not being able to be interrupted
- •Transplant of an organ other than the kidney
- •Type I or type II diabetes mellitus
- •Past medical history of granulomatosis or active granulomatosis
- •Primary hyperoxaluria
- •Malabsorption proved by the liposoluble vitamins
- •Simultaneous participation in another therapeutic essay
- •Patients presenting a drug addiction or a psychiatric disorder
- •Pregnant or breast-feeding women
- •Vitamin D hyper sensibility
研究组 & 干预措施
Cholecalciferol 100 000 UI
Cholecalciferol 100 000 UI FORTHIGHTLY for 2 months then monthly for 22 months
干预措施: Cholecalciferol 100 000 UI (Drug)
Cholecalciferol 12 000 UI (Control)
Cholecalciferol 12 000 UI FORTHIGHTLY for 2 months then monthly for 22 months.
干预措施: Cholecalciferol 12 000 UI (Drug)
结局指标
主要结局
De novo diabetes mellitus
时间窗: 2 years
De novo diabetes mellitus (fasting glycemia \> 7 mmoles/l or glycemia \> 11 mmoles/l)
Patient death
时间窗: 2 years
Cardiovascular complications
时间窗: 2 years
Cardiovascular complications (acute coronary heart disease, acute heart failure, lower-extremity arterial disease, cerebrovascular disease).
De novo cancer
时间窗: 2 years
Diagnosis of the incidence of any new cancer
次要结局
- Echocardiography findings(2 years)
- Blood pressure control(2 years)
- Acute rejection episode(2 years)
- Graft survival(2 years)
- Renal allograft function(2 years)
- Infection including opportunistic(2 years)
- Phosphocalcic biological and clinical relevant parameters(2 years)
- Renal lithiasis(2 years)