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

End Stage Renal Disease Clinical Trial

— VIKIPEDIA  

Official title:

Vitamin K In PEritonial DIAlysis (VIKIPEDIA)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04900610
• Other study ID #: 235/14.05.2021
• Status: Not yet recruiting
• Phase: N/A
• Start date: September 2021
• Est. completion date: September 2022

Study information

• Verified date: May 2021
• Source: Aristotle University Of Thessaloniki
• Contact: Stefanos Roumeliotis, MD, PhD
• Phone: +302313303110
• Email: st_roumeliotis[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 120
• Est. completion date: September 2022
• Est. primary completion date: June 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Arterial Stiffness
• Cardiovascular Morbidity
• End Stage Renal Disease
• Kidney Diseases
• Kidney Failure, Chronic
• Mortality
• Peritoneal Dialysis
• Vitamin K Deficiency

Intervention

Dietary Supplement:
• MenaQ7 ®, Nattopharma, ASA, Hovik, Norway
daily per os supplementation of 1mg MK-7

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Aristotle University Of Thessaloniki	Nattopharma ASA

References & Publications (7)

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 — View Citation

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 (18)F-Sodium Fluo — View Citation

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). pii: E628. doi: 1 — View Citation

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 — View Citation

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: 10.2174/15701611186662003201117 — View Citation

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. Hyperten — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression of arterial stifness	Change in pulse wave velocity	1.5 years
Primary	Non fatal cardiovascular events	Number of patients presenting acute myocardial infarction, acute coronary syndrome, embolism, peripheral arterial disease and stroke	1.5 years
Secondary	Mortality	Number of participants who willl die from any cause	1.5 years
Secondary	PD adequacy	Number of patients with preserved residual renal function	1.5 years
Secondary	PD clearance	Change in Kt/V	1.5 years
Secondary	Infections/peritonitis	Rate of infections and peritonitis	1.5 years
Secondary	Parathormone homeostasis	Changes in serum parathormone	1.5 year
Secondary	Calcium phosphorus homeostasis	Changes in the calcium phosphorus product	1.5 year
Secondary	Fractures	Incidence of fractures	1.5 years
Secondary	Joint/muscle pain	Incidence of pain in muscles and/or joints	1.5 years
Secondary	24-hour ambulatory BP/aortic systolic BP	Change in indices of ambulatory BP and aortic systolic blood pressure	1.5 years