Does Vitamin D3 (Cholecalciferol) Supplementation Change Insulin Resistance in Patients With Chronic Kidney Disease?
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Change in M-value (mg/kg lean body mass/min) assessed by insulin-glucose clamp
研究概览
简要总结
The purpose of this study is to evaluate the impact of vitamin D3 supplementation on the insulin resistance in non-diabetic patients with chronic kidney disease (CKD) stages 3-4, vitamin D deficiency/insufficiency and elevated fasting serum insulin levels.
详细描述
Insulin resistance, i.e., reduction in insulin responsiveness with a decrease in glucose uptake in insulin target tissues (muscle and adipose tissue) is common in end-stage renal disease (ESRD), but is also present at earlier stages of renal disease with mild-moderate renal function impairment as well as in microalbuminuria and nephrotic syndrome.
Population-based cross-sectional studies have shown that low levels of vitamin D (25(OH) vitamin D) is associated with impaired glucose tolerance in subjects with normal renal function and that reduced renal function and 25(OH) vitamin D deficiency are independently associated with insulin resistance.
Vitamin D has well-known effects on calcium metabolism and skeletal mineralisation but recent experimental studies suggest that vitamin D in addition reduces several inflammatory mediators that are of importance in the development and progression of renal disease which also associated with insulin resistance such as TNF-α and IL-6.
This is a prospective, single-blind, explorative, randomized, placebo-controlled, single-centre, two-way cross-over study with two treatment periods of 10 weeks separated by a washout period of 6 weeks. Non-diabetic patients with chronic kidney disease (CKD) stage 3 and 4 (GFR 15-60 ml/min/1.73m2) who have low serum 25-OH-vitamin D levels (< 30 ng/mL) and elevated fasting serum insulin levels (>10 IU/L) will be randomized to receive either vitamin D3 (cholecalciferol) 3200U orally (tablets) daily or placebo.
Approximately 24 patients are going to complete the study. A pre-entry wash-out period of 6 weeks is needed for patents already on vitamin D treatment. An in vivo assessment of insulin secretion and insulin sensitivity will be made by insulin-glucose clamp at the end of each treatment period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, age older than 18 years
- •Non-diabetic chronic kidney disease stage 3 and 4 (GFR 15-60 ml/min/1.73 m2)
- •Serum 25(OH) vitamin D < 30 ng/mL (75 nmol/L)
- •Fasting S-insulin > 30 IU/L
- •Written informed consent before entered into study
排除标准
- •Patients with current significant, major or unstable cardio-cerebrovascular, infection, respiratory, gastrointestinal or other major disease and risks according to the judgment made by the investigator
- •Patients with type 1 or type 2 Diabetes
- •Current severe thyrotoxicosis or other endocrine disease
- •Granulomatous disease, such as sarcoidosis and tuberculosis
- •Patients who are intended to receive hemodialysis (HD), peritoneal dialysis (PD) or being kidney transplanted during the course of study (9 months)
- •Concomitant use of corticosteroids (except for inhalation or topical use) or other immunosuppressive medication
- •Treatment with biphosphonate during last two years
- •S-Calcium > 2.70 mmol/L (0.68 mg/dl)
- •PTH intact < 75 ng/L (8.25 nmol/L) or > 800 ng/L (88 nmol/L)
- •Proteinuria > 3.5 g/24 hours
- •Alcohol or drug abuse or any condition associated with poor compliance
- •Blood donors
- •Women of childbearing potential, desired pregnancy, pregnancy or lactation within the study period
- •Allergy or intolerance to cholecalciferol supplementation (TillVal D®) or other constituents
- •Participation in a clinical trial evaluating an investigational drug in the last 12 weeks prior to inclusion to this trial
- •History of kidney stones
- •History of chronic hepatitis or liver enzymes (ASAT or ALAT) more than 2.5 times the upper limit of normal
- •Gastrointestinal disease resulting in significant gastrointestinal dysfunction or malabsorption
- •Use of medications known to interact with vitamin D metabolism such as cholestyramine, phenytoin, digitalis and antacids
- •Planned vacation with "high sun exposure" during the study period
研究组 & 干预措施
A
Vitamin D3 1600 IU orally twice daily
干预措施: cholecalciferol (TillVal-D) (Drug)
B
Placebo orally twice daily
干预措施: Placebo (Drug)
结局指标
主要结局
Change in M-value (mg/kg lean body mass/min) assessed by insulin-glucose clamp
时间窗: at week 26
次要结局
- Change in systolic- and diastolic blood pressure(at week 26)
- Change in PTH secretion and its fragments assessed by PTH, CAP-PTH, CIP-PTH(at week 26)
- Change in insulin secretion assessed by intravenous glucose tolerance test(at week 26)
- Change in urinary excretion of albumin (UAE) assessed by 24 hour collection(at week 26)