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

Not Applicable

• Conditions: Peritoneal Dialysis; Mortality; Vitamin K Deficiency; End Stage Renal Disease; Arterial Stiffness; Cardiovascular Morbidity
• Interventions: Dietary Supplement: MenaQ7 ®, Nattopharma, ASA, Hovik, Norway

• Registration Number: NCT04900610
• Lead Sponsor: Aristotle University Of Thessaloniki

Brief Summary

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

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).

Study Timeline

• Status Verified: 2021-05
• Study First Submitted: 2021-05-19
• Study First Submitted QC: 2021-05-24
• Last Update Submitted: 2021-05-24
• Study First Posted: 2021-05-25
• Last Update Posted: 2021-05-25
• Study Start: 2021-09
• Primary Completion: 2022-06
• Study Completion: 2022-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 120

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	MenaQ7 ®, Nattopharma, ASA, Hovik, Norway	matching placebo
Vitamin K2	MenaQ7 ®, Nattopharma, ASA, Hovik, Norway	1mg/day per os

Primary Outcome Measures

Name	Time	Method
Progression of arterial stifness	1.5 years	Change in pulse wave velocity
Non fatal cardiovascular events	1.5 years	Number of patients presenting acute myocardial infarction, acute coronary syndrome, embolism, peripheral arterial disease and stroke

Secondary Outcome Measures

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