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

Vitamin K In PEritonial DIAlysis (VIKIPEDIA)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Mortality; Peritoneal Dialysis; End Stage Renal Disease; Arterial Stiffness; Cardiovascular Morbidity; Vitamin K Deficiency
• Intervention / Treatment: Dietary supplement: MenaQ7 ®, Nattopharma, ASA, Hovik, Norway

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 Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Stefanos Roumeliotis, MD, PhD; Phone Number: +302313303110; Email: st_roumeliotis@hotmail.com
• Study Contact Backup: Name: Vassilios Liakopoulos, Professor; Phone Number: +302313303110; Email: liakopul@otenet.gr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; matching placebo	Dietary supplement: MenaQ7 ®, Nattopharma, ASA, Hovik, Norway; daily per os supplementation of 1mg MK-7
ACTIVE_COMPARATOR: Vitamin K2; 1mg/day per os	Dietary supplement: MenaQ7 ®, Nattopharma, ASA, Hovik, Norway; daily per os supplementation of 1mg MK-7

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Aristotle University Of Thessaloniki
• Collaborators: Nattopharma ASA
• Investigators: Principal Investigator: Stefanos Roumeliotis, MD, PhD, 1st Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki; Principal Investigator: Vassilios Liakopoulos, Professor, 1st Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki

Publications and helpful links

General Publications

• Roumeliotis S, Roumeliotis A, Dounousi E, Eleftheriadis T, Liakopoulos V. Vitamin K for the Treatment of Cardiovascular Disease in End-Stage Renal Disease Patients: Is there Hope? Curr Vasc Pharmacol. 2021;19(1):77-90. doi: 10.2174/1570161118666200320111745.
• Roumeliotis S, Dounousi E, Eleftheriadis T, Liakopoulos V. Association of the Inactive Circulating Matrix Gla Protein with Vitamin K Intake, Calcification, Mortality, and Cardiovascular Disease: A Review. Int J Mol Sci. 2019 Feb 1;20(3):628. doi: 10.3390/ijms20030628.
• Roumeliotis S, Dounousi E, Salmas M, Eleftheriadis T, Liakopoulos V. Vascular Calcification in Chronic Kidney Disease: The Role of Vitamin K- Dependent Matrix Gla Protein. Front Med (Lausanne). 2020 Apr 24;7:154. doi: 10.3389/fmed.2020.00154. eCollection 2020.
• Xu Q, Guo H, Cao S, Zhou Q, Chen J, Su M, Chen S, Jiang S, Shi X, Wen Y. Associations of vitamin K status with mortality and cardiovascular events in peritoneal dialysis patients. Int Urol Nephrol. 2019 Mar;51(3):527-534. doi: 10.1007/s11255-019-02080-x. Epub 2019 Jan 28.
• Peeters FECM, van Mourik MJW, Meex SJR, Bucerius J, Schalla SM, Gerretsen SC, Mihl C, Dweck MR, Schurgers LJ, Wildberger JE, Crijns HJGM, Kietselaer BLJH. Bicuspid Aortic Valve Stenosis and the Effect of Vitamin K2 on Calcification Using 18F-Sodium Fluoride Positron Emission Tomography/Magnetic Resonance: The BASIK2 Rationale and Trial Design. Nutrients. 2018 Mar 21;10(4):386. doi: 10.3390/nu10040386.
• Haroon SW, Tai BC, Ling LH, Teo L, Davenport A, Schurgers L, Teo BW, Khatri P, Ong CC, Low S, Yeo XE, Tan JN, Subramanian S, Chua HR, Tan SY, Wong WK, Lau TW. Treatment to reduce vascular calcification in hemodialysis patients using vitamin K (Trevasc-HDK): A study protocol for a randomized controlled trial. Medicine (Baltimore). 2020 Sep 4;99(36):e21906. doi: 10.1097/MD.0000000000021906.
• Vaios V, Georgianos PI, Vareta G, Dounousi E, Dimitriadis C, Eleftheriadis T, Papagianni A, Zebekakis PE, Liakopoulos V. Clinic and Home Blood Pressure Monitoring for the Detection of Ambulatory Hypertension Among Patients on Peritoneal Dialysis. Hypertension. 2019 Oct;74(4):998-1004. doi: 10.1161/HYPERTENSIONAHA.119.13443. Epub 2019 Aug 12.
• Roumeliotis S, Roumeliotis A, Georgianos PI, Thodis E, Schurgers LJ, Maresz K, Eleftheriadis T, Dounousi E, Tripepi G, Mallamaci F, Liakopoulos V. VItamin K In PEritonial DIAlysis (VIKIPEDIA): Rationale and study protocol for a randomized controlled trial. PLoS One. 2022 Aug 17;17(8):e0273102. doi: 10.1371/journal.pone.0273102. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): September 1, 2021
• Primary Completion (ANTICIPATED): June 1, 2022
• Study Completion (ANTICIPATED): September 1, 2022

Study Registration Dates

• First Submitted: May 19, 2021
• First Submitted That Met QC Criteria: May 24, 2021
• First Posted (ACTUAL): May 25, 2021

Study Record Updates

• Last Update Posted (ACTUAL): May 25, 2021
• Last Update Submitted That Met QC Criteria: May 24, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: End Stage Renal Disease; Chronic Kidney Disease; Cardiovascular; Peritoneal dialysis; Vitamin K; Menaquinone-7; Arterial stifness
• Additional Relevant MeSH Terms: Urologic Diseases; Hematologic Diseases; Renal Insufficiency; Nutrition Disorders; Hemorrhagic Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Renal Insufficiency, Chronic; Blood Coagulation Disorders; Kidney Diseases; Kidney Failure, Chronic; Vitamin K Deficiency
• Other Study ID Numbers: 235/14.05.2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No