Vitamin K to Slow Progression of Cardiovascular Disease Risk in Hemodialysis Patients

Study Overview
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Brief Summary
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The life span of adults with end-stage renal disease is reduced, and cardiovascular disease (CVD) accounts for approximately half the deaths among those undergoing hemodialysis (HD). Vascular calcification is a key process in the development of atherosclerotic and arteriosclerotic CVD, and contributes significantly to the greater mortality rates and CVD events in HD patients. Recently, there has been growing interest in the vitamin K-dependent matrix Gla protein (MGP) and its role in inhibiting vascular calcification. Animal studies have revealed that the vitamin K-dependent protein MGP may reduce the progression of vascular calcification, possibly by means of improving vascular function. The relationship between MGP and vitamin K lies in the fact that inactive matrix Gla protein requires vitamin K to carboxylate it for its activation. Currently, data in HD patients are scant and equivocal on the effects of vitamin K supplementation on CVD risk outcomes. Therefore, the purpose of this 8-week randomized, placebo-controlled, double-blind clinical trial is to determine whether daily vitamin K supplementation can favorably alter measurements of endothelial function and arterial stiffness in HD patients.

Official Title
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Vitamin K to Slow Progression of Cardiovascular Disease Risk in Hemodialysis Patients (Vita-K 'n' CKD Study)

Conditions
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Vitamin K Deficiency, Cardiovascular Diseases, Chronic Kidney Disease Stage 3, Chronic Kidney Disease Stage 4, Chronic Kidney Disease Stage 5, Hemodialysis

Intervention / Treatment
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* Dietary Supplement: Vitamin K2 (menaquinone-7; 360-mcg/d)
* Dietary Supplement: Placebo-Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic Kidney Disease Stages 3 to 5 Receiving hemodialysis treatment for at least 3 months Subject understands the study protocol and agrees to comply with it Informed consent documents signed by subject Exclusion Criteria: Using vitamin supplements containing vitamin K History of metabolic gastrointestinal diseases Subjects presenting chronic degenerative and/or inflammatory diseases Receiving systemic treatment or topical treatment likely to interfere with evaluation of the study parameters (salicylates, antibiotics) Subjects receiving corticosteroid Use of anticoagulants History of soy allergy Have an unstable medical condition, such as having a life expectancy of less than 6 months in the judgment of the investigator Known sensitivity, intolerance, or other adverse response to study drugs which would prevent compliance with study medication Subjects who have participated in a clinical study more recently than one month before the current 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo-Control<br>The placebo-control group will take four placebo softgel capsules (similar in taste and appearance to the vitamin K2 supplements) every day for 8 weeks. | Dietary Supplement: Placebo-Control<br>* four placebo softgel capsules per day for 8 weeks containing no vitamin K2 (menaquinone-7)<br>|
| Experimental: Vitamin K2 (360-mcg/d)<br>The experimental group will take four 90-mcg of vitamin K2 (menaquinone-7; 360-mcg) softgel capsules every day for 8 weeks. | Dietary Supplement: Vitamin K2 (menaquinone-7; 360-mcg/d)<br>* four 90-mcg vitamin K2 (menaquinone-7) softgel capsules per day for 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Flow-Mediated Dilation (FMD) | The FMD test is non-invasive assessment of vascular endothelial function. | Change from baseline to 8 weeks | 
| Pulse Wave Velocity (PWV) | The PWV test is a non-invasive test of arterial stiffness. | Change from baseline to 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prothrombin Time | The prothrombin time test is a measurement of clotting time. | Change from baseline to 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Arterial Stiffness, Endothelial Function, Vitamin K