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Effect of Vitamin K2 (MK7) on Cardiovascular and Bone Disease in Dialysis Patients (RenaKvit)

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ClinicalTrials.gov Identifier: NCT02976246
Recruitment Status : Recruiting
First Posted : November 29, 2016
Last Update Posted : November 29, 2016
Sponsor:
Information provided by (Responsible Party):
Zealand University Hospital

Brief Summary:

Cardiovascular disease (CVD) is the most frequent cause of death in patients (ptt.) with chronic kidney disease (CKD). Compared to the general population death due to CVD is 10-20 times higher in CKD ptt. being treated with hemodialysis. Vascular calcification and hence arterial stiffness is of great importance for the high incidence of CVD.

CKD ptt. in dialysis treatment also have a 3 times higher risk of bone fractures. Both vertebral and other fractures of low energy are associated with a high mortality.

Matrix Gla Protein (MGP) is an important inhibitor of vascular calcification and Osteocalcin (OC) is an important regulator of bone metabolism. The function of both MGP and OC depend on vitamin K.

Vitamin K is supplied with food. The content is low in food recommended to CKD ptt. which is reflected in very low concentrations of vitamin K in their blood samples. A correlation between vitamin K level, incidence of vascular calcification and bone density has been proven; yet there are no trials elucidating the clinical effect of vitamin K on vascular calcification or bone strength.

The investigators will conduct a randomized placebo controlled trial examining the clinical effects of vitamin K2 on vascular calcification and bone mineralization in order to prevent and treat CVD and bone disease in CKD ptt.

Primary study endpoints:

  1. Changes in arterial stiffness assessed by pulse wave examination
  2. Changes in bone mineral density (BMD) in distal radius assessed by DXA-scans.

Secondary study endpoints:

Changes in coronary artery and valvular calcification assessed by heart-CT-scans, blood pressure, body composition, total and regional BMD, lateral column/aortic calcification score as well as a panel of correlating blood tests.


Condition or disease Intervention/treatment Phase
Vitamin K Supplementation Endstage Renal Disease Cardiovascular Disease Bone Disease Dietary Supplement: Vitamin K2 (MK7) Other: Placebo Phase 2 Phase 3

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of Vitamin K2 (MK7) on Cardiovascular and Bone Disease in Dialysis Patients: A Prospective, Randomized Placebo-controlled Double Blind Trial
Study Start Date : November 2016
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : August 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Menadione

Arm Intervention/treatment
Active Comparator: RenaKvit-vessel Active
One tablet of 360 micrograms vitamin K2 given once daily to examine the effect on vascular calcification
Dietary Supplement: Vitamin K2 (MK7)
One tablet of vitamin K2 (MK7) 360 micrograms given once daily.
Other Names:
  • menaquinon 7
  • MK7

Placebo Comparator: RenaKvit-vessel Control
One tablet of non-active drug given once daily
Other: Placebo
One tablet of placebo given once daily.

Active Comparator: RenaKvit-bone Active
One tablet of 360 micrograms vitamin K2 given once daily to examine the effect on bone metabolism
Dietary Supplement: Vitamin K2 (MK7)
One tablet of vitamin K2 (MK7) 360 micrograms given once daily.
Other Names:
  • menaquinon 7
  • MK7

Placebo Comparator: RenaKvit-bone control
One tablet of non-active drug given once daily
Other: Placebo
One tablet of placebo given once daily.




Primary Outcome Measures :
  1. For RenaKvit-vessel: Changes in arterial stiffness assessed by pulse wave examination reflecting vascular calcification (unit: m/s). [ Time Frame: 2 years ]
  2. For RenaKvit-bone: Changes in bone mineral density (BMD) in the distal radial bone (unit T-score). [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. For RenaKvit-vessel: Changes in coronary vascular and -valve calcification assessed by CT-scans of the heart (unit: Agatston-Score). [ Time Frame: 2 years ]
  2. For RenaKvit-vessel: Changes in vascular calcification measured by changes in blood pressure measurements (unit: mmHg). [ Time Frame: 2 years ]
  3. For RenaKvit-bone: Changes in body composition, BMD in the lumbar column, hip and whole body (unit: T-score). [ Time Frame: 2 years ]
  4. For RenaKvit-bone: Changes in abdominal aortic calcification measured by lateral X-ray of lumbar column (unit: abdominal aortic calcification score). [ Time Frame: 2 years ]

Other Outcome Measures:
  1. For both RenaKvit-vessel and bone: Changes in specific biochemical markers in blood related to increase in vitamin K-treatment (unit mol/L) [ Time Frame: 2 years ]
    Measuring levels of vitamin K1, vitamin K2, de-/phosphorylated stages of MGP and OC, PIVKA-II, FGF-23, bone specific alkaline phosphatase, CTx-1, P1NP.

  2. For both RenaKvit-vessel and bone: Changes in non-specific biochemical markers in blood related to increase in vitamin K-treatment (unit/L) [ Time Frame: 2 years ]
    Measuring levels of creatinine, urea, ionic calcium, phosphate, 25-OH vitamin D, 1,25-OH2-vitamin D, PTH, sodium, potassium, total CO2, magnesium, HGB, white cells, platelets, ferritin, iron, transferrin, HS CRP, cholesterol, ALT, LDH, alkaline phosphatase, bilirubin, albumin, APTT, haptoglobin, trombingeneration (CAT), F1 + F2.

  3. For both RenaKvit-vessel and bone: Changes in urine production [ Time Frame: 2 years ]
    Monitoring volume, creatinine, urea, protein, albumin.

  4. For both RenaKvit-vessel and bone: Changes in medication [ Time Frame: 2 years ]
    Monitoring phosphate binders, vitamin D analogues, calcimimetics, antihypertensives, cholesterol-lowering drugs.

  5. For both RenaKvit-vessel and bone: monitoring clinical events expected to have relation to trial outcomes. [ Time Frame: 2 years ]

    Monitoring thromboembolic events, bone fractures, parathyroidectomy, death A selection of clinical events will be monitored (occurrence of bone fractures, thromboembolic events, parathyroidectomy as well as changes in medicine consumption during the trial calculated in DDD) and clinical consultations will be held.

    In order to register a potential change during treatment with vitamin K all of the above mentioned are to be performed regularly.




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18 years old
  • Life expectancy > 2 years
  • Written consent following oral information
  • Permanent treatment with dialysis ≥ 3 months with either peritoneal or hemodialysis

Exclusion Criteria:

  • Treatment with vitamin K or vitamin K-antagonist by the beginning of the trial or 1 months within.
  • Chronic GI-malabsorption leading to a slower bowel transit (e.g. Celiac disease, Short bowel syndrome).
  • Ongoing malignancy (ongoing treatment/clinical controlled visits or diagnosed less than 5 years ago), excl. Non-Melanoma-Skin-Cancer (NMSC).
  • Abuse of alcohol or other euphoric drug.
  • Women who are pregnant or breast-feeding and women who are in the childbearing age without contraception.
  • Total/subtotal parathyroidectomy
  • Treatment with recombined PTH.
  • Treatment with bisphosphonates or other anti-osteoporotic drugs (Selective Estrogen Reuptake Modulators (SERM), strontium, renalat, denosumab).

Only RenaKvit-kar (vessel):

  • Atrial fibrillation/other arrhythmia of significance
  • Aortic stenosis of significance
  • Agatston score < 100 by heart-CT-scan
  • Bilateral upper arm fistula
  • Amputation above metatarsal level

Criteria of withdrawal:

  • Kidney transplantation
  • Starting treatment with vitamin K-antagonists
  • Wish to with draw from the participant
  • Unacceptable side effect to ingestion of vitamin K or placebo
  • Reasonable suspicion of lacking compliance regarding medication

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02976246


Contacts
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Contact: Karin Levy-Schousboe, phd student +45 2335 1803 kshb@regionsjaelland.dk
Contact: Peter Marckmann, MDS +45 2335 1228 pmar@regionsjaelland.dk

Locations
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Denmark
Holbaek Hospital Not yet recruiting
Holbaek, Denmark, 4300
Contact: Marianne Berthelsen, MDS       mbte@regionsjaelland.dk   
Zealand University Hospital Recruiting
Roskilde, Denmark, 4000
Contact: Karin Levy-Schousboe, phd student    +45 23351803    kshb@regionsjaelland.dk   
Contact: Peter Marckmann, MDS    +45 23351228    pmar@regionsjaelland.dk   
Sponsors and Collaborators
Zealand University Hospital
Investigators
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Study Director: Peter Marckmann, MDS Zealand University Hospital
Study Director: Ditte Hansen, MDS Herlev Hospital
Study Director: Marie Frimodt-Moeller, MDS Steno Diabetes Center Copenhagen

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Responsible Party: Zealand University Hospital
ClinicalTrials.gov Identifier: NCT02976246     History of Changes
Other Study ID Numbers: RenaKvit
First Posted: November 29, 2016    Key Record Dates
Last Update Posted: November 29, 2016
Last Verified: November 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Additional relevant MeSH terms:
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Bone Diseases
Kidney Failure, Chronic
Cardiovascular Diseases
Kidney Diseases
Urologic Diseases
Musculoskeletal Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Vitamins
Vitamin K
Vitamin K 2
Vitamin MK 7
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Hemostatics
Coagulants