Study of Vitamin D3 Supplementation in Patients With Chronic Kidney Disease

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Does Vitamin D3 (Cholecalciferol) Supplementation Change Insulin Resistance in Patients With Chronic Kidney Disease?

Conditions
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Chronic Kidney Disease, Insulin Resistance, Vitamin D Deficiency

Intervention / Treatment
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* Drug: cholecalciferol (TillVal-D)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br>Vitamin D3 1600 IU orally twice daily | Drug: cholecalciferol (TillVal-D)<br>* In a randomized, two-way cross-over design participants will take vitamin D3 or placebo twice daily during treatment periods of 10 weeks separated by a washout period of 6 weeks.<br>* Other names: TillVal-D, cholecalciferol, vitamin D3;|
| Placebo Comparator: B<br>Placebo orally twice daily | Drug: Placebo<br>* Placebo orally twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in M-value (mg/kg lean body mass/min) assessed by insulin-glucose clamp |  | at week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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renal disease, renal impairment, chronic kidney disease stage 3-4, 25(OH) vitamin D, cholecalciferol, vitamin D deficiency, insulin resistance, insulin-glucose clamp, non-diabetic