Oral Paricalcitol in Stage 3 - 5 Chronic Kidney Disease

Study Overview
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Brief Summary
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The purpose of this study is to test the hypothesis that selective vitamin D receptor activation reduces left ventricular hypertrophy and ameliorates inflammation and atherosclerosis in stage 3 -5 chronic kidney disease.

Detailed Description
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Cardiovascular disease is the leading cause of mortality and morbidity in patients with chronic kidney disease. According to a previous study, only 15.6% of the patients beginning dialysis therapy had a normal echocardiogram, with left ventricular hypertrophy, left ventricular dilatation and systolic dysfunction occurring in 40.7%, 28% and 15.6% of patients, respectively. In addition, these patients are at an accelerated risk of developing atherosclerosis. The Kidney Disease Outcome Quality Initiative guideline recently raised concerns of a high prevalence of vitamin D deficiency in chronic kidney disease patients not yet requiring dialysis treatment. In addition, very recent data suggested that vitamin D deficiency is an important predictor of mortality in end-stage renal disease patients. Furthermore, hemodialysis patients treated with paricalcitol, a selective vitamin D receptor activator, showed a significantly lower risk of cardiovascular death than those not receiving vitamin D therapy. A number of studies also showed positive benefit of vitamin D receptor activator treatment on regression of left ventricular hypertrophy in dialysis patients. However, there is so far no data in patients with stage 3 and 4 chronic kidney disease where a high prevalence of vitamin D deficiency and cardiac hypertrophy has been reported.

Official Title
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A Prospective, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy of Oral Paricalcitol in Retarding Cardiac Hypertrophy, Reducing Inflammation and Atherosclerosis in Stage 3 - 5 Chronic Kidney Disease

Conditions
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Chronic Kidney Disease

Intervention / Treatment
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* Drug: paricalcitol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with stage 3 -5 chronic kidney disease (that is, eGFR < 60 ml/min per 1.73m2) diagnosed for more than 2 months and not expected to start dialysis within the next 12 months, and Patient with screening echocardiography showing evidence of left ventricular hypertrophy Patient has not received vitamin D therapy in the previous 4 weeks For entry into the Treatment Phase, the subject must have: screening iPTH >= 55 pg/ml or 5.8pmol/L (determined by the Nichols second-generation assay or similar assay) serum calcium < 10.2 mg/dL (2.55 mmol/L) serum phosphorus =< 5.2mg/dL (1.68mmol/L) Ca*P product < 54 mg2/dL2 (4.36mmol2/L2) If female, subject is either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), or is of childbearing potential and practicing birth control measures. Patients who provide informed consent for the study Exclusion Criteria: Patient with a history of an allergic reaction or significant sensitivity to vitamin D or vitamin D related compounds. Patient with history of renal stones Patient with current malignancy Patients with clinically significant gastrointestinal disease or liver disease Patient with acute renal failure in the recent three months Patient with a history of drug or alcohol abuse within six months prior to the screening phase Patient is known to be human immunodeficiency virus (HIV) positive. Patient with evidence of poor compliance with diet and medication. Patient currently receiving medications that may affect calcium, phosphorus metabolism such as calcitonin, cinacalcet, bisphophonates or vitamin D compounds (other than study drug), or other drugs that may affect calcium or bone metabolism, other than females on stable estrogen and/or progestin therapy. Patients with active granulomatous disease Patient with pregnancy Patients currently receiving glucocorticoid steroid or other immunosuppressive treatment or had been administered glucocorticoid or other immunosuppressive treatment for more than 14 days within recent 6 months. Patients with contraindication for MRI examination

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>paricalcitol | Drug: paricalcitol<br>* oral paricalcitol capsule 1 microgram once daily if iPTH <500pg/mL or 2 microgram once daily if iPTH >=500pg/mL. Thereafter, dose titration in 1 microgram decrement will be done based on safety reasons (that is, for low PTH or high calcium and phosphorus level). The duration of treatment will be for 1 year.<br>* Other names: Zemplar;|
| Placebo Comparator: 2<br>placebo | Drug: paricalcitol<br>* oral paricalcitol capsule 1 microgram once daily if iPTH <500pg/mL or 2 microgram once daily if iPTH >=500pg/mL. Thereafter, dose titration in 1 microgram decrement will be done based on safety reasons (that is, for low PTH or high calcium and phosphorus level). The duration of treatment will be for 1 year.<br>* Other names: Zemplar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in left ventricular mass index determined by MRI |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in left atrial and ventricular volumes, systolic and diastolic function, carotid intima-media thickness, flow mediated dilation, pulse wave velocity, serum inflammatory and cardiac biomarkers, intact PTH, 24-hour urine protein and renal function |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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paricalcitol, chronic kidney disease, cardiac hypertrophy