Study of Vitamin D3 Supplementation in Patients With Chronic Kidney Disease

Insulin Resistance Clinical Trial

— VitaD-CKD1  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00893451
• Other study ID #: VitaD-CKD1
• Status: Completed
• Phase: N/A
• First received: May 5, 2009
• Last updated: June 9, 2011
• Start date: September 2009
• Est. completion date: June 2011

Study information

• Verified date: June 2011
• Source: Sahlgrenska University Hospital, Sweden
• Contact: n/a
• Is FDA regulated: No
• Health authority: Sweden: Regional Ethical Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: June 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Insulin Resistance
• Kidney Diseases
• Renal Insufficiency, Chronic
• Vitamin D Deficiency

Intervention

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.
• Placebo
Placebo orally twice daily

Locations

Country	Name	City	State
Sweden	Department of Kidney diseases, Sahlgrenska University Hospital	Gothenburg

Sponsors (1)

Lead Sponsor	Collaborator
Sahlgrenska University Hospital, Sweden

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in M-value (mg/kg lean body mass/min) assessed by insulin-glucose clamp		at week 26	No
Secondary	Change in systolic- and diastolic blood pressure		at week 26	No
Secondary	Change in PTH secretion and its fragments assessed by PTH, CAP-PTH, CIP-PTH		at week 26	No
Secondary	Change in insulin secretion assessed by intravenous glucose tolerance test		at week 26	No
Secondary	Change in urinary excretion of albumin (UAE) assessed by 24 hour collection		at week 26	No