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
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
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
NCT ID
NCT04900610
First Posted
May 19, 2021
Last Updated
May 24, 2021
Sponsor
Aristotle University Of Thessaloniki
Collaborators
Nattopharma ASA
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
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The Effect of Vitamin K2 Supplementation on Arterial Stifness and Cardiovascular Events in PEritonial DIAlysis
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