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

NCT ID: NCT04900610

Last Updated: 2021-05-25

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-30
• Study Completion Date: 2022-09-30

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).

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Vitamin K2

1mg/day per os

Group Type: ACTIVE_COMPARATOR

MenaQ7 ®, Nattopharma, ASA, Hovik, Norway

Intervention Type: DIETARY_SUPPLEMENT

daily per os supplementation of 1mg MK-7

Placebo

matching placebo

Group Type: PLACEBO_COMPARATOR

MenaQ7 ®, Nattopharma, ASA, Hovik, Norway

Intervention Type: DIETARY_SUPPLEMENT

daily per os supplementation of 1mg MK-7

Interventions

MenaQ7 ®, Nattopharma, ASA, Hovik, Norway

daily per os supplementation of 1mg MK-7

Intervention Type: DIETARY_SUPPLEMENT

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nattopharma ASA

INDUSTRY

Sponsor Role: collaborator

Aristotle University Of Thessaloniki

OTHER

Sponsor Role: lead

Responsible Party

Vaios Vasileios

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Stefanos Roumeliotis, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

1st Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki

Vassilios Liakopoulos, Professor

Role: PRINCIPAL_INVESTIGATOR

1st Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki

Central Contacts

Stefanos Roumeliotis, MD, PhD

Role: CONTACT

st_roumeliotis@hotmail.com

+302313303110

Vassilios Liakopoulos, Professor

Role: CONTACT

liakopul@otenet.gr

+302313303110

References

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.

Reference Type: RESULT

PMID: 32196451 (View on PubMed)

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.

Reference Type: RESULT

PMID: 30717170 (View on PubMed)

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.

Reference Type: RESULT

PMID: 32391368 (View on PubMed)

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.

Reference Type: RESULT

PMID: 30689181 (View on PubMed)

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.

Reference Type: RESULT

PMID: 29561783 (View on PubMed)

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.

Reference Type: RESULT

PMID: 32899022 (View on PubMed)

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.

Reference Type: RESULT

PMID: 31401878 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35976944 (View on PubMed)

Other Identifiers

235/14.05.2021

Identifier Type: -

Identifier Source: org_study_id