Anti-proteinuric Effect of Calcitriol in Non-diabetic Kidney Disease Patients

Study Overview
=================
Brief Summary
-----------------
Proteinuria is not only a marker of chronic kidney disease (CKD) progression, but also a marker of cardiovascular disease and death. In previous studies, active vitamin D deficiency is associated with cardiovascular risk factors such as albuminuria, diabetes mellitus, and lower glomerular filtration rate (GFR). And calcitriol was shown to have a preventive effect in progressive glomerular damage in a renal ablation model. Calcitriol, an active form of vitamin D (1,25-dihydroxyvitamin-D3), is commonly used for the treatment of secondary hyperparathyroidism in patients with advanced chronic kidney diseases. Therefore, the objective of this study is to evaluate the anti-proteinuric effect of calcitriol in non-diabetic kidney disease patients. They will be treated with calcitriol and placebo for 24 weeks and observed for 24 weeks after treatment. Proteinuria, renal function, serum and urinary inflammatory markers, and adverse event will be monitored.

Official Title
-----------------
Additive Renoprotective Effects of Oral Calcitriol in Nondiabetic Chronic Kidney Disease Patients

Conditions
-----------------
Proteinuria

Intervention / Treatment
-----------------
* Drug: Calcitriol
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Nondiabetic kidney disease patients aged 19-70 years MDRD GFR ≥ 30 mL/min/1.73m2 Patients with residual urine protein/creatinine ratio > 200 mg/g Adequate blood pressure control as treated systolic blood pressure <=140 or diastolic <=90 mmHg with RAS inhibitor for more than 3 months Normotensive patients untreated with RAS inhibitors Serum intact PTH as 35-500 mg/dL and serum calcium less than 10.2 mg/dL Patients who have not been treated vitamin D within the 3 months prior to signing the informed consent form Exclusion Criteria: Patients with nephrotic-range proteinuria (24 hour urine protein >3.5 g/24 hr) Patients with rapidly progressive glomerulonephritis Patients requiring renal replacement therapy immediately Hypercalcemia (uncorrected serum calcium level > 10.2 mg/dL) within 3 months Malignant hypertension Heart failure (New York Heart Association [NYHA] functional class II to IV or LVEF less than 40%) Severe chronic obstructive lung disease Decompensated liver disease Known allergy or hypersensitivity to vitamin D Current treatment with steroids and/or immunosuppressive agents No other active primary malignancy requiring treatment or that limits survival to ≤ 2 years History of noncompliance to medical regimen Inability to give an informed consent or to cooperate with researchers (e.g., psychiatric disorder)

Ages Eligible for Study
-----------------
Minimum Age: 19 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Calcitriol<br> | Drug: Calcitriol<br>* Dosage of 0.25 mcg administered orally once daily for 6 weeks and dose escalated to 0.5 mcg orally once daily up to 6 months<br>* Other names: Calcio® (Hanmi Pharm Co., Korea);|
| No Intervention: Placebo<br> | Drug: Placebo<br>* Dosage of 0.25 mcg administered orally once daily for 6 weeks and dose escalated to 0.5 mcg orally once daily up to 6 months<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in proteinuria | Comparison of proteinuria amount checked by random urine protein/creatinine ratio | 6, 12 months after administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in renal function | Comparison of in serum creatinine level from baseline | 3, 6, 9 and 12 months | 
| Changes in urinary renal damage markers | Comparison of urinary TGF-beta, TNF-alpha, MCP-1 level from baseline | 6, 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Calcitriol, Off-label