Vitamin-D Receptor Activation (VDRA) in Chronic Kidney Disease

Study Overview
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Brief Summary
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To investigate whether treatment with a vitamin-D receptor activator is able to improve important markers of cardiovascular risk.

Detailed Description
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Main question: May 12 weeks of VDRA treatment reduce the pathological sympathetic overactivation associated with moderate kidney disease? Secondary questions aim to thrown light on how VDRAs can reduce albuminuria and CRP, i.e. does VDRA treatment improve (prespecified statistical analyses): A) diastolic dysfunction? B) capillary microcirculation, and whether ameliorated disturbances relate to improved diastolic dysfunction? C) endothelial dysfunction and arterial stiffness? D) inflammatory activation? E) platelet function and haemostasis? F) levels of antibacterial peptides? G) levels of IGFBP-1 and adiponectin? Overall design The study is designed as a double-blind, randomised, placebo-controlled trial involving two groups (n=72) of patients: 1) chronic kidney failure (CKD, eGFR 15-59 mL/m2) and 2) chronic kidney failure and concomitant diabetes mellitus (CKD+DM). It will start with a two-week placebo run-in, followed by randomisation to: Zemplar 1 μg (taken as 1 x 1 μg capsule and one placebo capsule), Zemplar 2 μg (taken as 2 x 1 μg capsules) and placebo (taken as two placebo capsules).

Official Title
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Diastolic Dysfunction, Microcirculation Disturbance, Sympathetic Activation and Inflammation in Moderate Kidney Failure and in Diabetic Nephropathy: Disease Modification With Vitamin-D Receptor Activation. A Double-blind, Placebo-controlled, Randomised Trial - the SOLID Trial

Conditions
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Chronic Kidney Disease

Intervention / Treatment
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* Drug: Zemplar


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: eGFR 15-59 ml/m2 Exclusion Criteria: Current vitamin D treatment

Ages Eligible for Study
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Minimum Age: 20 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 |
| --- | --- |
| Active Comparator: Paricalcitol 2 microgram/d<br> | Drug: Zemplar<br>* Vitamin D receptor activator (VDRA)<br>|
| Active Comparator: Paricalcitol 1 microgram/d<br> | Drug: Zemplar<br>* Vitamin D receptor activator (VDRA)<br>|
| Placebo Comparator: Placebo<br> | Drug: Zemplar<br>* Vitamin D receptor activator (VDRA)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A significant reduction in muscle sympathetic nerve activity (MSNA) measured by means of microneurography. | Sympathetic activation is closely related to severity and progression of cardiovascular diseases, and renovascular dysfunction. We will directly measure sympathetic activation using microneurography (muscle sympathetic nerve activity; MSNA), expressed as bursts/minute and bursts/100 RR-interval. As this is a physiological study, the primary outcome will constitute a significant reduction in MSNA. | Measured after 12 weeks treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microcirculatory function measured by laser doppler methods. | Assessed by skin laser-doppler methodology, and directly by nailfold capillaroscopy. | Measured after 12 weeks treatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dysfunction in CKD