The Effect of Vitamin K2 Supplementation on Arterial Stifness and Cardiovascular Events in PEritonial DIAlysis

Study Overview
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Brief Summary
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VIKIPEDIA is a multi-centre, placebo-controlled, randomized, open-label intervention clinical trial on Peritoneal Dialysis (PD) patients. At baseline the investigators will recruit End-Stage Renal Disease patients undergoing PD and randomize them to either daily per os supplementation of 1mg menaquinone-7 or placebo for 1.5 year. The investigators will study the effect of vitamin K2 supplementation (through normalization of dp-ucMGP) on arterial stifness and the occurence of cardiovascular events. The investigators will also cosider as secondary endpoints, mortality, central aortic blood pressure and indices of 24h-ambulatory blood pressure.

Detailed Description
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VIKIPEDIA is a multi-centre, placebo-controlled, randomized, open-label intervention clinical trial on PD patients. The study protocol was developed in accordance with the Helsinki Declaration of Human Rights and the Good Clinical Practice Guidelines and Standard Protocol Items: Recommendations for Intervention Trials, was approved by the Ethics Committee/Scientific Council of the Medical School of Aristotle University of Thessaloniki (235/14.05.2021) All participants will provide a structured, written, informed consent. Three university, tertiary hospitals in Northern Greece with major, referral PD units will participate in the study. The patients will be recruited within 1 year. At baseline, all eligible patients who have provided a written, informed consent will be enrolled in the study. Αortic stiffness and vitamin K status will be assessed by PWV and plasma dp-ucMGP levels respectively. Before randomization, the investigators will draw blood (serum and plasma) and PD fluid samples from all patients to measure blood count and routine biochemical parameters, including urea, creatinine, potassium, sodium, calcium, phosphorus, c-reactive protein, alkaline phosphatase, albumin, parathormone, 25-OH D3, magnesium, glycated hemoglobin, thyroid function hormones. Since both vitamin D and magnesium are considered of utmost importance in vitamin K metabolism, after baseline, patients with vitamin D and/or magnesium depletion will be treated with oral supplements to achieve normal levels of both elements, before randomization. The cohort will then be categorized to one of the two groups (placebo or active group) and the treatment period will last 1.5 years. To ensure that the two parallel groups will include patients that will not differ significantly in vitamin K and stiffness, patients will be accordingly stratified. After randomization, all patients will continue their routine, standard medical treatment and patients in the treatment group will additionally receive daily, per os 1 mg of vitamin K2 (MenaQ7 ®, Nattopharma, ASA, Hovik, Norway).

Official Title
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Vitamin K In PEritonial DIAlysis (VIKIPEDIA)

Conditions
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Mortality, Vitamin K Deficiency, End Stage Renal Disease, Peritoneal Dialysis, Arterial Stiffness, Cardiovascular Morbidity

Intervention / Treatment
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* Dietary Supplement: MenaQ7 ®, Nattopharma, ASA, Hovik, Norway


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years At least 3 months on PD Life expectancy of ≥ 18 months Exclusion Criteria: Liver disease Drug or alcohol abuse Pregnancy or breast-feeding Treatment with phosphate binders (sevelamer) Ongoing malignancy or severe inflammatory disease diagnosis Use of vitamin K antagonist or vitamin K supplements during the past 3 months Diagnosis of severe gut-disease (inflammatory or short bowel disease) or gastrointestinal malabsorption Mental disorder rendering the patient unable to conform with the instructions and fully understand the nature, aim and possible side-effects of the supplementation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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
Interventional Model Description: Multi-centre, placebo-controlled, randomized, open-label intervention clinical trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vitamin K2<br>1mg/day per os | Dietary Supplement: MenaQ7 ®, Nattopharma, ASA, Hovik, Norway<br>* daily per os supplementation of 1mg MK-7<br>|
| Placebo Comparator: Placebo<br>matching placebo | Dietary Supplement: MenaQ7 ®, Nattopharma, ASA, Hovik, Norway<br>* daily per os supplementation of 1mg MK-7<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression of arterial stifness | Change in pulse wave velocity | 1.5 years | 
| Non fatal cardiovascular events | Number of patients presenting acute myocardial infarction, acute coronary syndrome, embolism, peripheral arterial disease and stroke | 1.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | Number of participants who willl die from any cause | 1.5 years | 
| PD adequacy | Number of patients with preserved residual renal function | 1.5 years | 
| PD clearance | Change in Kt/V | 1.5 years | 
| Infections/peritonitis | Rate of infections and peritonitis | 1.5 years | 
| Parathormone homeostasis | Changes in serum parathormone | 1.5 year | 
| Calcium phosphorus homeostasis | Changes in the calcium phosphorus product | 1.5 year | 
| Fractures | Incidence of fractures | 1.5 years | 
| Joint/muscle pain | Incidence of pain in muscles and/or joints | 1.5 years | 
| 24-hour ambulatory BP/aortic systolic BP | Change in indices of ambulatory BP and aortic systolic blood pressure | 1.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiovascular, Chronic Kidney Disease, End Stage Renal Disease, Vitamin K, Menaquinone-7, Peritoneal dialysis, Arterial stifness