Clinical trial NCT00893451: Study of Vitamin D3 Supplementation in Patients With Chronic Kidney Disease
Official title: Does Vitamin D3 (Cholecalciferol) Supplementation Change Insulin Resistance in Patients With Chronic Kidney Disease?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Kidney Disease
Insulin Resistance
Vitamin D Deficiency
Keywords: 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
Lead sponsor: Sahlgrenska University Hospital
Sponsor class: OTHER
First posted: 2009-05-06
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in M-value (mg/kg lean body mass/min) assessed by insulin-glucose clamp
timeFrame: at week 26
Secondary outcomes:
measure: Change in systolic- and diastolic blood pressure
timeFrame: at week 26
measure: Change in PTH secretion and its fragments assessed by PTH, CAP-PTH, CIP-PTH
timeFrame: at week 26
measure: Change in insulin secretion assessed by intravenous glucose tolerance test
timeFrame: at week 26
measure: Change in urinary excretion of albumin (UAE) assessed by 24 hour collection
timeFrame: at week 26
Other outcomes:
Locations:
city: Gothenburg
country: Sweden
facility: Department of Kidney diseases, Sahlgrenska University Hospital
Study officials:
affiliation: Sahlgrenska University Hospital
name: Hamid R Dezfoolian, MD
role: PRINCIPAL_INVESTIGATOR
References: