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

Primary Purpose

Vitamin K Deficiency, End Stage Renal Disease, Peritoneal Dialysis

Status
Unknown status
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
MenaQ7 ®, Nattopharma, ASA, Hovik, Norway
Sponsored by
Aristotle University Of Thessaloniki
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Vitamin K Deficiency focused on measuring Vitamin K, Menaquinone-7, Peritoneal dialysis, Arterial stifness, Cardiovascular, Chronic Kidney Disease, End Stage Renal Disease

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Placebo Comparator

    Arm Label

    Vitamin K2

    Placebo

    Arm Description

    1mg/day per os

    matching placebo

    Outcomes

    Primary Outcome Measures

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

    Secondary Outcome Measures

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

    Full Information

    First Posted
    May 19, 2021
    Last Updated
    May 24, 2021
    Sponsor
    Aristotle University Of Thessaloniki
    Collaborators
    Nattopharma ASA
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04900610
    Brief Title
    The Effect of Vitamin K2 Supplementation on Arterial Stifness and Cardiovascular Events in PEritonial DIAlysis
    Acronym
    VIKIPEDIA
    Official Title
    Vitamin K In PEritonial DIAlysis (VIKIPEDIA)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    May 2021
    Overall Recruitment Status
    Unknown status
    Study Start Date
    September 2021 (Anticipated)
    Primary Completion Date
    June 2022 (Anticipated)
    Study Completion Date
    September 2022 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Aristotle University Of Thessaloniki
    Collaborators
    Nattopharma ASA

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. 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.
    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).

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Vitamin K Deficiency, End Stage Renal Disease, Peritoneal Dialysis, Arterial Stiffness, Cardiovascular Morbidity, Mortality
    Keywords
    Vitamin K, Menaquinone-7, Peritoneal dialysis, Arterial stifness, Cardiovascular, Chronic Kidney Disease, End Stage Renal Disease

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Model Description
    Multi-centre, placebo-controlled, randomized, open-label intervention clinical trial
    Masking
    Participant
    Allocation
    Randomized
    Enrollment
    120 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Vitamin K2
    Arm Type
    Active Comparator
    Arm Description
    1mg/day per os
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    matching placebo
    Intervention Type
    Dietary Supplement
    Intervention Name(s)
    MenaQ7 ®, Nattopharma, ASA, Hovik, Norway
    Intervention Description
    daily per os supplementation of 1mg MK-7
    Primary Outcome Measure Information:
    Title
    Progression of arterial stifness
    Description
    Change in pulse wave velocity
    Time Frame
    1.5 years
    Title
    Non fatal cardiovascular events
    Description
    Number of patients presenting acute myocardial infarction, acute coronary syndrome, embolism, peripheral arterial disease and stroke
    Time Frame
    1.5 years
    Secondary Outcome Measure Information:
    Title
    Mortality
    Description
    Number of participants who willl die from any cause
    Time Frame
    1.5 years
    Title
    PD adequacy
    Description
    Number of patients with preserved residual renal function
    Time Frame
    1.5 years
    Title
    PD clearance
    Description
    Change in Kt/V
    Time Frame
    1.5 years
    Title
    Infections/peritonitis
    Description
    Rate of infections and peritonitis
    Time Frame
    1.5 years
    Title
    Parathormone homeostasis
    Description
    Changes in serum parathormone
    Time Frame
    1.5 year
    Title
    Calcium phosphorus homeostasis
    Description
    Changes in the calcium phosphorus product
    Time Frame
    1.5 year
    Title
    Fractures
    Description
    Incidence of fractures
    Time Frame
    1.5 years
    Title
    Joint/muscle pain
    Description
    Incidence of pain in muscles and/or joints
    Time Frame
    1.5 years
    Title
    24-hour ambulatory BP/aortic systolic BP
    Description
    Change in indices of ambulatory BP and aortic systolic blood pressure
    Time Frame
    1.5 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    90 Years
    Accepts Healthy Volunteers
    No
    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
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Stefanos Roumeliotis, MD, PhD
    Phone
    +302313303110
    Email
    st_roumeliotis@hotmail.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Vassilios Liakopoulos, Professor
    Phone
    +302313303110
    Email
    liakopul@otenet.gr
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Stefanos Roumeliotis, MD, PhD
    Organizational Affiliation
    1st Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki
    Official's Role
    Principal Investigator
    First Name & Middle Initial & Last Name & Degree
    Vassilios Liakopoulos, Professor
    Organizational Affiliation
    1st Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    Citations:
    PubMed Identifier
    32196451
    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: 10.2174/1570161118666200320111745.
    Results Reference
    result
    PubMed Identifier
    30717170
    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):628. doi: 10.3390/ijms20030628.
    Results Reference
    result
    PubMed Identifier
    32391368
    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 2020.
    Results Reference
    result
    PubMed Identifier
    30689181
    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. Epub 2019 Jan 28.
    Results Reference
    result
    PubMed Identifier
    29561783
    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 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.
    Results Reference
    result
    PubMed Identifier
    32899022
    Citation
    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.
    Results Reference
    result
    PubMed Identifier
    31401878
    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. Hypertension. 2019 Oct;74(4):998-1004. doi: 10.1161/HYPERTENSIONAHA.119.13443. Epub 2019 Aug 12.
    Results Reference
    result
    PubMed Identifier
    35976944
    Citation
    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.
    Results Reference
    derived

    Learn more about this trial

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

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