Study of Vitamin D3 Supplementation in Patients With Chronic Kidney Disease (VitaD-CKD1)

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

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.

Study Overview

• Status: Completed
• Conditions: Vitamin D Deficiency; Insulin Resistance; Chronic Kidney Disease
• Intervention / Treatment: Drug: cholecalciferol (TillVal-D); Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Gothenburg, Sweden, 41345
    • Department of Kidney diseases, Sahlgrenska University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female, age older than 18 years
2. Non-diabetic chronic kidney disease stage 3 and 4 (GFR 15-60 ml/min/1.73 m2)
3. Serum 25(OH) vitamin D < 30 ng/mL (75 nmol/L)
4. Fasting S-insulin > 30 IU/L
5. Written informed consent before entered into study

Exclusion Criteria:

1. 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
2. Patients with type 1 or type 2 Diabetes
3. Current severe thyrotoxicosis or other endocrine disease
4. Granulomatous disease, such as sarcoidosis and tuberculosis
5. Patients who are intended to receive hemodialysis (HD), peritoneal dialysis (PD) or being kidney transplanted during the course of study (9 months)
6. Concomitant use of corticosteroids (except for inhalation or topical use) or other immunosuppressive medication
7. Treatment with biphosphonate during last two years
8. S-Calcium > 2.70 mmol/L (0.68 mg/dl)
9. PTH intact < 75 ng/L (8.25 nmol/L) or > 800 ng/L (88 nmol/L)
10. Proteinuria > 3.5 g/24 hours
11. Alcohol or drug abuse or any condition associated with poor compliance
12. Blood donors
13. Women of childbearing potential, desired pregnancy, pregnancy or lactation within the study period
14. Allergy or intolerance to cholecalciferol supplementation (TillVal D®) or other constituents
15. Participation in a clinical trial evaluating an investigational drug in the last 12 weeks prior to inclusion to this trial
16. History of kidney stones
17. History of chronic hepatitis or liver enzymes (ASAT or ALAT) more than 2.5 times the upper limit of normal
18. Gastrointestinal disease resulting in significant gastrointestinal dysfunction or malabsorption
19. Use of medications known to interact with vitamin D metabolism such as cholestyramine, phenytoin, digitalis and antacids
20. Planned vacation with "high sun exposure" during the study period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A; Vitamin D3 1600 IU orally twice daily	Drug: cholecalciferol (TillVal-D); 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.; Other Names: TillVal-D, cholecalciferol, vitamin D3
Placebo Comparator: B; Placebo orally twice daily	Drug: Placebo; Placebo orally twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Sahlgrenska University Hospital, Sweden
• Investigators: Principal Investigator: Hamid R Dezfoolian, MD, Sahlgrenska University Hospital, Sweden

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: May 5, 2009
• First Submitted That Met QC Criteria: May 5, 2009
• First Posted (Estimate): May 6, 2009

Study Record Updates

• Last Update Posted (Estimate): June 10, 2011
• Last Update Submitted That Met QC Criteria: June 9, 2011
• Last Verified: June 1, 2011

More Information

Terms related to this study

• Keywords: insulin resistance; renal impairment; vitamin D deficiency; cholecalciferol; renal disease; non-diabetic; chronic kidney disease stage 3-4; 25(OH) vitamin D; insulin-glucose clamp
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Urologic Diseases; Renal Insufficiency; Nutrition Disorders; Hyperinsulinism; Avitaminosis; Deficiency Diseases; Malnutrition; Kidney Diseases; Renal Insufficiency, Chronic; Vitamin D Deficiency; Insulin Resistance; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: VitaD-CKD1