NCT02976246

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

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
123

participants targeted

Target at P50-P75 for phase_4

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 2016

Completed
2 days until next milestone

First Submitted

Initial submission to the registry

November 3, 2016

Completed
26 days until next milestone

First Posted

Study publicly available on registry

November 29, 2016

Completed
3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 26, 2020

Completed
Last Updated

July 1, 2020

Status Verified

June 1, 2020

Enrollment Period

3.7 years

First QC Date

November 3, 2016

Last Update Submit

June 29, 2020

Conditions

Vitamin K SupplementationEndstage Renal DiseaseCardiovascular DiseaseBone Disease

Outcome Measures

Primary Outcomes (2)

  • For RenaKvit-vessel: Changes in arterial stiffness assessed by pulse wave examination reflecting vascular calcification (unit: m/s).

    2 years

  • For RenaKvit-bone: Changes in bone mineral density (BMD) in the distal radial bone (unit T-score).

    2 years

Secondary Outcomes (4)

  • For RenaKvit-vessel: Changes in coronary vascular and -valve calcification assessed by CT-scans of the heart (unit: Agatston-Score).

    2 years

  • For RenaKvit-vessel: Changes in vascular calcification measured by changes in blood pressure measurements (unit: mmHg).

    2 years

  • For RenaKvit-bone: Changes in body composition, BMD in the lumbar column, hip and whole body (unit: T-score).

    2 years

  • For RenaKvit-bone: Changes in abdominal aortic calcification measured by lateral X-ray of lumbar column (unit: abdominal aortic calcification score).

    2 years

Other Outcomes (5)

  • For both RenaKvit-vessel and bone: Changes in specific biochemical markers in blood related to increase in vitamin K-treatment (unit mol/L)

    2 years

  • For both RenaKvit-vessel and bone: Changes in non-specific biochemical markers in blood related to increase in vitamin K-treatment (unit/L)

    2 years

  • For both RenaKvit-vessel and bone: Changes in urine production

    2 years

  • +2 more other outcomes

Study Arms (4)

RenaKvit-vessel Active

ACTIVE COMPARATOR

One tablet of 360 micrograms vitamin K2 given once daily to examine the effect on vascular calcification

Dietary Supplement: Vitamin K2 (MK7)

RenaKvit-vessel Control

PLACEBO COMPARATOR

One tablet of non-active drug given once daily

Other: Placebo

RenaKvit-bone Active

ACTIVE COMPARATOR

One tablet of 360 micrograms vitamin K2 given once daily to examine the effect on bone metabolism

Dietary Supplement: Vitamin K2 (MK7)

RenaKvit-bone control

PLACEBO COMPARATOR

One tablet of non-active drug given once daily

Other: Placebo

Interventions

Vitamin K2 (MK7)DIETARY_SUPPLEMENT

One tablet of vitamin K2 (MK7) 360 micrograms given once daily.

Also known as: menaquinon 7, MK7
RenaKvit-bone ActiveRenaKvit-vessel Active
PlaceboOTHER

One tablet of placebo given once daily.

RenaKvit-bone controlRenaKvit-vessel Control

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • 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:
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Zealand University Hospital

Roskilde, 4000, Denmark

Location

MeSH Terms

Conditions

Cardiovascular DiseasesBone Diseases

Interventions

Vitamin K 2

Condition Hierarchy (Ancestors)

Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Vitamin KNaphthoquinonesNaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPhytolDiterpenesTerpenesQuinonesPolycyclic Compounds

Study Officials

  • Peter Marckmann, MDS

    Zealand University Hospital

    STUDY DIRECTOR

  • Ditte Hansen, MDS

    Herlev Hospital

    STUDY DIRECTOR

  • Marie Frimodt-Moeller, MDS

    Steno Diabetes Center Copenhagen

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 3, 2016

First Posted

November 29, 2016

Study Start

November 1, 2016

Primary Completion

June 26, 2020

Last Updated

July 1, 2020

Record last verified: 2020-06

Locations

DK(1)