Salt Intake and Antiproteinuric Effect of Paricalcitol in Type 2 Diabetes

Study Overview
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Brief Summary
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Proteinuria is an independent risk factor for cardiovascular morbidity and mortality and for renal disease progression. More proteinuria is associated with faster progression, whereas treatments that reduce proteinuria are renoprotective in both diabetic and non diabetic chronic kidney disease. Of note, lower the residual proteinuria achieved by treatment slower is the disease progression in the long term. On the basis of the above findings, proteinuria has become a target of renoprotective therapy. Among different antihypertensive medications, those that inhibit the Renin Angiotensin System, such as angiotensin converting enzyme (ACE)inhibitors and angiotensin receptor blockers (ARBs), are those that at comparable blood pressure control, more effectively reduce proteinuria and slow renal disease progression. Thus they have become the key component of renoprotective therapy in patients with proteinuric chronic kidney disease. Observational studies found that their effectiveness, however, is limited or even fully blunted in patients who eat large amount of salt. Experimental evidence indicates a renoprotective role of the vitamin D system in chronic renal disease. A recent randomized, controlled trial, add-on therapy with selective Vitamin D receptor activator paricalcitol showed an additive antiproteinuric effect in subjects with type 2 diabetes and chronic kidney disease on background Renin-angiotensin-system inhibitor therapy. This effect, however, was largely restricted to subjects with daily sodium intake exceeding 12 grams and was negligible in those with lower sodium intake. Thus, treatment with paricalcitol appears to be effective in particular in those patients who do not appreciably benefit of renin angiotensin system (RAS) inhibitors therapy because of high salt intake. Thus, whether the antiproteinuric effect of paricalcitol is modified by concomitant salt intake in patients with chronic kidney disease (CKD) on background RAS inhibitors therapy, is worth investigating. The broad aim of this study is to evaluate the interaction between paricalcitol therapy and sodium intake in type 2 diabetes patients with proteinuric kidney disease on stable background RAS inhibitor therapy.

Official Title
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A Prospective, Randomized, Cross-over, Double-blind, Placebo-controlled Study to Assess the Antiproteinuric Effect of Selective Vitamin d Receptor Activation by Paricalcitol in Type 2 Diabetes Patients on Low or High Sodium Diet and Stable Ras Inhibitor Therapy

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Paricalcitol
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients; Age > 18 years; Type 2 diabetes patients on low or high sodium diet and stable RAS inhibitor therapy with the following conditions: Urinary albumin excretion (UAE) rate >300mg/24 hours (200 mcg/min); Serum creatinine <2 mg/dL, PTH ≥ 20 mEq/L and <110 mEq/L; Calcium and phosphorus levels < 9.5 mg/dl and < 5mg/dl, respectively; Controlled BP (systolic/diastolic <140/90 mmHg) while on stable RAS inhibitor therapy; - Written informed consent. Exclusion Criteria: Previous Vitamin D or Vitamin D analogs therapy (within 3 months prior to the study entry); Evidence of toxicity to Vitamin D; History of kidney stones; Poorly controlled Diabetes: Hb1Ac > 12%; Therapy with calcitonin, bisphosphonates, cinacalcet, glucocorticoids, immunosuppressive drugs or other drug that may affect calcium or bone metabolism; Cancer and any severe systemic disease or clinical condition that may jeopardize data interpretation or completion of the study; Any clinically relevant conditions that might affect study participation and/or study results; Any contraindication to be exposed to Paricalcitol; Pregnancy or lactating; Women of childbearing potential without following a scientifically accepted form of contraception; Legal incapacity.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paricalcitol<br> | Drug: Paricalcitol<br>* 1-month Paricalcitol 2mcg/day<br>|
| Placebo Comparator: placebo<br> | Other: placebo<br>* 1-month Placebo Treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in urinary albumin excretion from baseline at 4 month. |  | At baseline and 1,2,3 and 4 month. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ambulatory and 24-hour blood pressure profile. |  | At 1 month. | 
| Ambulatory and 24-hour blood pressure profile. |  | At 2 month. | 
| Ambulatory and 24-hour blood pressure profile. |  | At 3 month. | 
| Ambulatory and 24-hour blood pressure profile. |  | At 4 month. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 diabetes, Paricalcitol, Proteinuria, Sodium intake