Effect Of Paricalcitol (Zemplar) On Endothelial Function And Inflammation In Type 2 Diabetes And Chronic Kidney Disease

Study Overview
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Brief Summary
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The purpose of this research study is to study the effects of paricalcitol on endothelial function and inflammation, cardiovascular risk factors which are associated with patient populations that have Type 2 diabetes and Stage 3 and 4 Chronic Kidney Disease (CKD). Hypothesis 1: The state of CKD is associated with oxidative stress and inflammation and impaired post ischemic endothelium dependent flow mediated vasodilation which may contribute to atherogenesis. Hypothesis 2: The administration of paracalcitol to patients with CKD will suppress oxidative stress and inflammation and improve endothelial function and thus contribute to an anti-atherogenic action.

Official Title
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EFFECT OF PARICALCITOL (ZEMPLAR) ON ENDOTHELIAL FUNCTION AND INFLAMMATION IN TYPE 2 DIABETES AND CHRONIC KIDNEY DISEASE

Conditions
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Type 2 Diabetes, Chronic Kidney Disease

Intervention / Treatment
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* Drug: Zemplar
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with Type 2 diabetes and CKD Age 18 - 70 years Stable anti-hypertensive and lipid lowering therapy for at least 2 months. All patients should be on an ACEI or ARB unless contraindicated because of side effects (standard of care). No changes in lipid lowering therapy during the 3 months of this study. Blood pressure doses may be changed but new therapy with ACE inhibitors will not be allowed. Exclusion Criteria: Severe co morbid conditions - e.g. Cancer, etc. Congestive heart failure. Inability to give informed consent or attend study related visits. Have a history of abnormally high vitamin D or calcium levels in the bloodstream. Unwilling or unable to complete screening or data collection procedures. Have a known allergy to the study drug. Pregnant or breast feeding Plasma Calcium >9 mg/dl Patients should discontinue any calcium supplementation prior to entry into the study. Other vitamin D analogs (eg Sensipar) and vitamin D preparations are contraindicated

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Diagnostic
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Zemplar<br>Zemplar 1 mcg or placebo to be taken once daily with breakfast for 3 months | Drug: Zemplar<br>* Zemplar 1 mcg or placebo to be taken once daily with breakfast for 3 months<br>|
| Placebo Comparator: Placebo<br>Zemplar 1 mcg or placebo to be taken once daily with breakfast for 3 months | Drug: Placebo<br>* Zemplar 1 mcg or placebo to be taken once daily with breakfast for 3 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in brachial artery Flow Mediated Dilataion with paracalcitol (1mcg/day)compared with placebo for 3 months. | We therefore propose a study of the effects of Zemplar compared to placebo in patients with diabetes and stage 3-4 CKD on endothelial function and markers of inflammation and oxidative stress. The finding will help not only guide and encourage such treatment in similar patients, but will give us fundamental mechanistic insights into the role of vitamin D in the pathogenesis of diabetes and CVD. | Baseline, 4 weeks, and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarker Measurement | Determine the prevalance of abnormalities in biomarkers of inflammation, oxidative stress and endothelial function in patients with CKD compared to a healthy population The following are the biomarkers of inflammation and oxidative stress to be measured in the secondary outcomes are: NFkB binding by mononuclear cells (MNC) ; ROS generation and p47phox expression by MNC plasma concentration of MMP-9, MCP-1, ICAM-1, IL-6 , CRP, ADMA and nitrotyrosine.. urinary isoprostane and plasma Nitrotyrosine in patients with CKD. | Baseline, 4 weeks, and 12 weeks | 
| Biomarker Measurement | Compare the change in biomarkers of inflammation, oxidative stress and endothelial function with paracalcitol (1mcg/day) compared with placebo for 3 months in patients with CKD. The following are the biomarkers of inflammation and oxidative stress to be measured in the secondary outcomes are: NFkB binding by mononuclear cells (MNC) ; ROS generation and p47phox expression by MNC plasma concentration of MMP-9, MCP-1, ICAM-1, IL-6 , CRP, ADMA and nitrotyrosine.. urinary isoprostane and plasma Nitrotyrosine in patients with CKD. | Baseline, 4 weeks, and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stage 3 chronic kidney disease (CKD), Stage 4 chronic kidney disease (CKD), CKD