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

• ClinicalTrials.gov Identifier: NCT04900610
• Recruitment Status: Unknown
• First Posted: May 25, 2021
• Last Update Posted: May 25, 2021
• Sponsor: Aristotle University Of Thessaloniki
• Collaborator: Nattopharma ASA
• Information provided by (Responsible Party): Vaios Vasileios, Aristotle University Of Thessaloniki

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Vitamin K Deficiency; End Stage Renal Disease; Peritoneal Dialysis; Arterial Stiffness; Cardiovascular Morbidity; Mortality	Dietary Supplement: MenaQ7 ®, Nattopharma, ASA, Hovik, Norway	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Multi-centre, placebo-controlled, randomized, open-label intervention clinical trial
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Vitamin K In PEritonial DIAlysis (VIKIPEDIA)
• Estimated Study Start Date: September 2021
• Estimated Primary Completion Date: June 2022
• Estimated Study Completion Date: September 2022

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Vitamin K2; 1mg/day per os	Dietary Supplement: MenaQ7 ®, Nattopharma, ASA, Hovik, Norway; daily per os supplementation of 1mg MK-7
Placebo Comparator: Placebo; matching placebo	Dietary Supplement: MenaQ7 ®, Nattopharma, ASA, Hovik, Norway; daily per os supplementation of 1mg MK-7

Outcome Measures

Primary Outcome Measures :

1. Progression of arterial stifness [ Time Frame: 1.5 years ]
   Change in pulse wave velocity
2. Non fatal cardiovascular events [ Time Frame: 1.5 years ]
   Number of patients presenting acute myocardial infarction, acute coronary syndrome, embolism, peripheral arterial disease and stroke

Secondary Outcome Measures :

1. Mortality [ Time Frame: 1.5 years ]
   Number of participants who willl die from any cause
2. PD adequacy [ Time Frame: 1.5 years ]
   Number of patients with preserved residual renal function
3. PD clearance [ Time Frame: 1.5 years ]
   Change in Kt/V
4. Infections/peritonitis [ Time Frame: 1.5 years ]
   Rate of infections and peritonitis
5. Parathormone homeostasis [ Time Frame: 1.5 year ]
   Changes in serum parathormone
6. Calcium phosphorus homeostasis [ Time Frame: 1.5 year ]
   Changes in the calcium phosphorus product
7. Fractures [ Time Frame: 1.5 years ]
   Incidence of fractures
8. Joint/muscle pain [ Time Frame: 1.5 years ]
   Incidence of pain in muscles and/or joints
9. 24-hour ambulatory BP/aortic systolic BP [ Time Frame: 1.5 years ]
   Change in indices of ambulatory BP and aortic systolic blood pressure

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 90 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Stefanos Roumeliotis, MD, PhD; +302313303110; st_roumeliotis@hotmail.com

Contact: Vassilios Liakopoulos, Professor; +302313303110; liakopul@otenet.gr

Sponsors and Collaborators

Aristotle University Of Thessaloniki

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

More Information

Publications of Results:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Vaios Vasileios, Principal Investigator, Aristotle University Of Thessaloniki
• ClinicalTrials.gov Identifier: NCT04900610
• Other Study ID Numbers: 235/14.05.2021
• First Posted: May 25, 2021
• Last Update Posted: May 25, 2021
• Last Verified: May 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Vaios Vasileios, Aristotle University Of Thessaloniki:

Vitamin K; Menaquinone-7; Peritoneal dialysis; Arterial stifness; Cardiovascular; Chronic Kidney Disease; End Stage Renal Disease

Additional relevant MeSH terms:

Kidney Diseases; Kidney Failure, Chronic; Vitamin K Deficiency; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Chronic Disease; Disease Attributes; Pathologic Processes; Blood Coagulation Disorders; Hematologic Diseases; Hemorrhagic Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders