Vitamin K2 Supplementation and Vascular Calcification

Study Overview
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Brief Summary
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Vascular calcification is the leading cause of death in patients with end stage renal disease (ESRD) in hemodialysis. The protein matrix Gla vitamin K dependent (MGP) is a potent inhibitor of the vascular calcification. Objective: To evaluate the effect of vitamin K2 on vascular calcification in patients on hemodialysis. Materials and Methods: A prospective, randomized, double-blind study will be performed. The study subjects will be divided into a control (1000 µl of saline) or treated group (1000 µl containing 2000 µg of Vitamin K2). Vitamin K2 will be administered three times a week intravenously at the end of each dialysis session. Blood samples for biochemical determinations and vascular calcification will be assessed before and after 6 months of treatment through carotid Doppler ultrasound.

Detailed Description
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This study is designed according to the ethical reference framework for biomedical research of the Declaration of Helsinki. Its design is prospective, randomized, double blind. Study subjects will be assigned either Arm 1 or control (vial with 1000 μL of saline) or Arm 2 or treated group (vial with 1000 μL containing 2000 μg of Vitamin K2). The trial protocol was approved by the ethics committee of the Catholic University of Salta and written informed consent will be made available to all patients who agree to participate and meet the inclusion criteria. Vascular calcification will be evaluated at the beginning of the study to determine the presence of vascular calcification and at the end of the study to assess changes, if any. The carotid artery examination will be performed with a GE VIVID 5 (GE Healthcare, Little Chalfont, Buckinghamshire, UK) with a 7.5 MHz linear probe. The protocol used to obtain images is consistent with the recommendations of the American Society of Echocardiography. Longitudinal images will be obtained by means of B-mode ultrasound, the maximum and the global median intima thickness (EIM) value of the common carotid artery and the presence of carotid plaques (defined as isolated and focal areas of the abnormal intima that protrude into the lumen more than 1.5 mm or at least 50% of the surrounding total mean intimate value). The EIM represents the thickness of the intima, plus the component of the mean of the vessel wall; with an automated computerized system of the equipment, on the distal wall of both common carotid arteries, 1 cm below the carotid bulb, along a 10 mm long straight arterial segment. Patients may be stratified into 3 groups according to the EIM value: EIM patients with <0.5 mm are considered disease-free; patients with IMD between 0.6-1 mm will be considered to be non-significantly affected by the disease; patients with IMD> 1 mm will be grouped as affected by significant disease (Table 1). Therefore, carotid atherosclerosis is considered in the presence of plaques or an EIM> 1 mm. 2.5.3 Table 1. Thickness of the intima plus the component of the mean in the wall of a vessel associated or not with the presence of vascular calcification. EIM VALUE Presence or not of vascular calcification <0,5 mm Patients without vascular calcification 0,6-1 mm Patients non-significantly affected by the disease > 1 mm Patients significantly affected by the disease

Official Title
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Effect of Vitamin K2 Supplementation on Vascular Calcification in Hemodialysis Patients: a Controlled Randomized Trial.

Conditions
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Renal Disease

Intervention / Treatment
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* Drug: Vitamin K 2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women ≥18 years old A period not less than 6 months in HD Life expectancy ≥ 18 months Signed informed consent Exclusion Criteria: Patients under treatment with phosphorus chelators Patients who do not want to participate in the study

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective, randomized, double-blind study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vitamn K2 Treated patients<br>Vitamin K2 will be given to patients randomized to ARM 1 three times a week at the end of each dialysis session to prevent it being lost through the ultrafiltration membrane (in order to use the same dialysis access) intravenously to ensure its bioavailability. | Drug: Vitamin K 2<br>* Patients will be monitored during the whole protocol.<br>* Other names: PLACEBO GROUP;|
| Placebo Comparator: Placebo Group<br>Placebo will be given to patients randomized three times a week to ARM 2 at the end of each dialysis session to prevent it being lost through the ultrafiltration membrane (in order to use the same dialysis access) intravenously to ensure its bioavailability. | Drug: Vitamin K 2<br>* Patients will be monitored during the whole protocol.<br>* Other names: PLACEBO GROUP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EFFECT OF VITAMIN K2 ON VASCULAR CALCIFICATION | Changes in the VC (changes in the intimate thickness of carotide artery versus baseline). | 6 months | 
| CHANGES IN THE PRODUCT PHOSPHORUS CALCIUM | Changes in the product phosphorus calcium versus baseline | 6 months | 
| CHANGES IN PTHi SERUM LEVELS | Not significant changes in PTHi serum levels versus baseline | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemodialysis patients, Vascular calcification, Vitamin K2