Paricalcitol for the Treatment of Immunoglobulin A Nephropathy

Study Overview
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Brief Summary
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Immunoglobulin A (IgA) nephropathy is the common type of primary glomerulonephritis in the world. A wealth of literature suggests that vitamin D and its analogs have profound effects on immune system function and glomerular mesangial cell proliferation. However, calcitriol, the standard form of vitamin D, carries a substantial risk of hypercalcemia. Recently, paricalcitol (19-nor-1,25-dihydroxyvitamin D2) was approved for the treatment of secondary hyperparathyroidism in chronic renal failure, and the incidence of hypercalcemia is much lower than calcitriol. Therefore, the investigators plan to conduct a randomized cross-over study to evaluate the efficacy of paricalcitol in the treatment of IgA nephropathy. Thirty patients with biopsy-proven IgA nephropathy will be recruited. They will be randomized to paricalcitol for 12 weeks or no treatment, followed by cross over to the other arm after a washout period. Proteinuria, renal function, serum and urinary inflammatory markers will be monitored. This study will explore the potential anti-proteinuric and anti-inflammatory effects of paricalcitol in the treatment of IgA nephropathy, which has no specific treatment at present.

Official Title
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Paricalcitol for the Treatment of Immunoglobulin A Nephropathy - A Randomized Cross-Over Study

Conditions
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IgA Nephropathy

Intervention / Treatment
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* Drug: paricalcitol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: aged 18-65 years biopsy-confirmed IgA nephropathy proteinuria > 1 g/day (or proteinuria > 1 g/g-Cr) in 3 consecutive samples within 12 weeks despite ACE inhibitor or angiotensin receptor blocker treatment (e.g. ramipril 5 mg daily, lisinopril 10 mg daily, or valsartan 80 mg daily) for at least 3 months estimated glomerular filtration rate > 60 ml/min/1.73m2 corrected serum calcium level > or = 2.45 mmol/l 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 Participation in any previous trial on paricalcitol Patients receiving treatment of vitamin D and/or its analogue for other medical reasons within the past 3 months Patients receiving treatment of corticosteroid 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 paricalcitol or other 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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>paricalcitol 1 mg/day for 12 weeks, followed by a washout period of 4 weeks, then crossed over to no treatment for another 12 weeks | Drug: paricalcitol<br>* paricalcitol 1 mg/day<br>|
| Active Comparator: 2<br>no treatment for 12 weeks, followed by a washout period of 4 weeks, then crossed over to paricalcitol for another 12 weeks | Drug: paricalcitol<br>* paricalcitol 1 mg/day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in the degree of proteinuria |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rate of decline of estimated GFR (as determined by the least square method) and change in other serum inflammatory markers |  | 12 weeks |