The Effect of Calcitriol on Progress and Activity of Lupus Nephritis

Study Overview
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Brief Summary
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The purpose of this study is to determine whether calcitriol is effective in the treatment of lupus nephritis.

Detailed Description
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Systemic lupus erythematosus (SLE) is an autoimmune disease and renal involvement represent one of the most common manifestations of it . On the other hand, there is evidence that vitamin D and its analogs have known immunosuppressant properties and profound effects on glomerular mesangial cell proliferation. Moreover much literature such as animal studies suggests it as a therapeutic intervention in autoimmune disease. The investigators plan to conduct a double blind randomized control clinical trial to study effects of calcitriol on progress and activity of lupus nephritis. Fifty patients with clinically quiescent SLE and biopsy-proven glomerulonephritis will be recruited. They will be treated with calcitriol for 1 year. Proteinuria, renal function, lupus disease activity, serum inflammatory markers will be monitored.

Official Title
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The Effect of Calcitriol on Progress and Activity of Lupus Nephritis

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: calcitriol
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18-65 years Baseline Systemic Lupus Erythematosus Disease Activity Index score <= 4 Estimated glomerular filtration rate more than 15 ml/min/1.73m2 Proteinuria > 1 g/day (or proteinuria > 1 g/g-Cr) in 2 consecutive samples within 12 weeks despite ACE inhibitor at least 3 months On maintenance dose of prednisolone < 15 mg/day with or without other immunosuppressive medications Serum calcium level in normal range( 8.5-10.5 mg/dl) History of biopsy-proven lupus nephritis clinical quiescent SLE for at least 3 month Willingness to give written consent and comply with the study protocol Exclusion Criteria: Pregnancy, lactating or childbearing potential without effective method of birth control Severe gastrointestinal disorders that interfere with their ability to receive or absorb oral medication History of malignancy, including leukemia and lymphoma within the past 2 years; Systemic infection requiring therapy at study entry Any other severe coexisting disease such as, but not limited to, chronic liver disease, myocardial infarction, cerebrovascular accident, malignant hypertension History of drug or alcohol abuse within past 2 years Vitamin D deficiency(25 hydroxy vitamin D less than 20ng/ml) Participation in any previous trial on vitamin D analogue Patients receiving treatment of vitamin D and/or its analogue for other medical reasons within the past 4 weeks Patients who are taking multivitamin supplement that contains vitamin D could be enrolled after 4 weeks of wash out period by changing to a preparation that has no vitamin D On other investigational drugs within last 30 days History of a psychological illness or condition such as to interfere with the patient's ability to understand the requirement of the study History of non-compliance; Known history of sensitivity or allergy to vitamin D analogs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: treatment group<br>Patients will receive calcitriol at a fixed dose daily. | Drug: calcitriol<br>* Patients will receive calcitriol at a fixed dose of 0.25 µg (one oral pearl) daily.<br>|
| Active Comparator: control group<br>Patients will receive placebo daily. | Drug: placebo<br>* Patients will receive placebo similar to intervention (shape, color and design) 1 oral unit daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in proteinuria |  | baseline and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| risk of lupus flare |  | baseline and 12 months | 
| change in renal function | based on the American College of Rheumatology renal response criteria | baseline and 12 months | 
| change in serum inflammatory markers |  | baseline and 12 months | 
| change in Systemic Lupus Erythematosus Disease Activity Index score |  | baseline and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lupus nephritis, proteinuria, SLE, calcitriol