Vitamin K2 Supplementation to Activate Matrix Gla Protein (MGP) as Endogenous Inhibitor of Vascular Calcification in Hemodialysis Patients
Primary Purpose
CKD 5D, Hemodialysis
Status
Completed
Phase
Phase 3
Locations
Germany
Study Type
Interventional
Intervention
daily supplementation of MK-7 over 6 weeks
Sponsored by
About this trial
This is an interventional basic science trial for CKD 5D, Hemodialysis focused on measuring vitamin K, MK-7, Hemodialysis, vascular calcification, Matrix Gla protein, Osteocalcin
Eligibility Criteria
Inclusion Criteria:
- > 18 years of age
- minimum of 3 months of hemodialysis
- written consent
Exclusion Criteria:
- chronic or acute bowel disease
- soy bean allergy
- active Vitamin K Supplementation
- oral anticoagulation with vitamin K Antagonists (coumarins)
- systemic therapy using steroids
- positive history for thrombosis or embolism
- pregnancy
Sites / Locations
- KfH Dialysis Unit Aachen
- University Hospital of the RWTH Aachen
- Dialysis Unit Erkelenz
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
45 µg MK-7
135 µg MK-7
360 µg MK-7
Arm Description
45 µg MK-7 daily over 6 weeks
135 µg MK-7 daily over 6 weeks
360 µg MK-7 daily over 6 weeks
Outcomes
Primary Outcome Measures
Reduction of plasma levels of noncarboxylated MGP
Noncarboxylated MGP levels [pmol/L] will be determined from plasma samples by a non-commercial ELISA. Plasma samples will be obtained each week of the six-week treatment period and compared to baseline values.
Reduction of plasma levels of noncarboxylated osteocalcin
Noncarboxylated osteocalcin levels [ng/ml] will be determined from plasma samples by a commercial ELISA. Plasma samples will be obtained each week of the six-week treatment period and compared to baseline values.
Reduction of plasma levels of inactive prothrombin (PIVKA-II)
PIVKA-II levels [ng/ml] will be determined from plasma samples by a commercial ELISA. Plasma levels at the end of the six-week treatment period will be compared to baseline levels.
Secondary Outcome Measures
increase of plasma levels of carboxylated MGP
Carboxylated MGP levels [pmol/L] will be determined from plasma samples by a non-commercial ELISA. Plasma samples will be obtained each week of the six-week treatment period and compared to baseline values.
increase of plasma levels of carboxylated osteocalcin
Carboxylated MGP levels [ng/ml] will be determined from plasma samples by a commercial ELISA. Plasma samples will be obtained each week of the six-week treatment period and compared to baseline values.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01407601
Brief Title
Vitamin K2 Supplementation to Activate Matrix Gla Protein (MGP) as Endogenous Inhibitor of Vascular Calcification in Hemodialysis Patients
Official Title
Food Supplementation With Vitamin K2 to Activate MGP as an Endogenous Inhibitor of Vascular Calcification in Hemodialysis Patients
Study Type
Interventional
2. Study Status
Record Verification Date
August 2011
Overall Recruitment Status
Completed
Study Start Date
January 2008 (undefined)
Primary Completion Date
May 2008 (Actual)
Study Completion Date
July 2009 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
RWTH Aachen University
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Vascular calcification (VC) is a predictor of cardiovascular morbidity and mortality. Hemodialysis (HD) patients suffer from severe vascular calcifications. Matrix Gla protein (MGP) is a central calcification inhibitor of the arterial wall and its activity depends on vitamin K-dependent γ-glutamate carboxylation. Noncarboxylated MGP, formed as a result of vitamin K deficiency, is associated with cardiovascular disease. Recent studies pointed towards poor vitamin K status in HD patients. We therefore aim to investigate whether daily vitamin K2 (MK-7) supplementation improves the bioactivity of vitamin K-dependent proteins in HD patients as assessed by circulating dephospho-noncarboxylated MGP (dp-ucMGP), noncarboxylated osteocalcin (ucOC) and noncarboxylated prothrombin (ucFII; PIVKA-II).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
CKD 5D, Hemodialysis
Keywords
vitamin K, MK-7, Hemodialysis, vascular calcification, Matrix Gla protein, Osteocalcin
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
53 (Actual)
8. Arms, Groups, and Interventions
Arm Title
45 µg MK-7
Arm Type
Experimental
Arm Description
45 µg MK-7 daily over 6 weeks
Arm Title
135 µg MK-7
Arm Type
Experimental
Arm Description
135 µg MK-7 daily over 6 weeks
Arm Title
360 µg MK-7
Arm Type
Experimental
Arm Description
360 µg MK-7 daily over 6 weeks
Intervention Type
Dietary Supplement
Intervention Name(s)
daily supplementation of MK-7 over 6 weeks
Intervention Description
once daily intake of MK-7 prior to dialysis over 6 weeks
Primary Outcome Measure Information:
Title
Reduction of plasma levels of noncarboxylated MGP
Description
Noncarboxylated MGP levels [pmol/L] will be determined from plasma samples by a non-commercial ELISA. Plasma samples will be obtained each week of the six-week treatment period and compared to baseline values.
Time Frame
after 6 weeks of supplementation
Title
Reduction of plasma levels of noncarboxylated osteocalcin
Description
Noncarboxylated osteocalcin levels [ng/ml] will be determined from plasma samples by a commercial ELISA. Plasma samples will be obtained each week of the six-week treatment period and compared to baseline values.
Time Frame
after 6 weeks of supplementation
Title
Reduction of plasma levels of inactive prothrombin (PIVKA-II)
Description
PIVKA-II levels [ng/ml] will be determined from plasma samples by a commercial ELISA. Plasma levels at the end of the six-week treatment period will be compared to baseline levels.
Time Frame
after 6 weeks of supplementation
Secondary Outcome Measure Information:
Title
increase of plasma levels of carboxylated MGP
Description
Carboxylated MGP levels [pmol/L] will be determined from plasma samples by a non-commercial ELISA. Plasma samples will be obtained each week of the six-week treatment period and compared to baseline values.
Time Frame
after 6 weeks of supplementation
Title
increase of plasma levels of carboxylated osteocalcin
Description
Carboxylated MGP levels [ng/ml] will be determined from plasma samples by a commercial ELISA. Plasma samples will be obtained each week of the six-week treatment period and compared to baseline values.
Time Frame
after 6 weeks of supplementation
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
> 18 years of age
minimum of 3 months of hemodialysis
written consent
Exclusion Criteria:
chronic or acute bowel disease
soy bean allergy
active Vitamin K Supplementation
oral anticoagulation with vitamin K Antagonists (coumarins)
systemic therapy using steroids
positive history for thrombosis or embolism
pregnancy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ralf Westenfeld, MD
Organizational Affiliation
University Clinic of the RWTH Aachen
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Georg Schlieper, MD
Organizational Affiliation
University Clinic of the RWTH Aachen
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Stefan Holzmann, MD
Organizational Affiliation
Dialysis Unit Erkelenz, Germany
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Stephan Heidenreich, MD
Organizational Affiliation
KfH Dialysis Centre Aachen, Schurzelter Strasse
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Juergen Floege, MD
Organizational Affiliation
University Clinic of the RWTH Aachen
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Thilo Krueger, MD
Organizational Affiliation
University Hospital of the RWTH Aachen
Official's Role
Study Chair
Facility Information:
Facility Name
KfH Dialysis Unit Aachen
City
Aachen
State/Province
NRW
ZIP/Postal Code
52074
Country
Germany
Facility Name
University Hospital of the RWTH Aachen
City
Aachen
State/Province
NRW
ZIP/Postal Code
52074
Country
Germany
Facility Name
Dialysis Unit Erkelenz
City
Erkelenz
State/Province
NRW
ZIP/Postal Code
41812
Country
Germany
12. IPD Sharing Statement
Citations:
PubMed Identifier
22169620
Citation
Westenfeld R, Krueger T, Schlieper G, Cranenburg EC, Magdeleyns EJ, Heidenreich S, Holzmann S, Vermeer C, Jahnen-Dechent W, Ketteler M, Floege J, Schurgers LJ. Effect of vitamin K2 supplementation on functional vitamin K deficiency in hemodialysis patients: a randomized trial. Am J Kidney Dis. 2012 Feb;59(2):186-95. doi: 10.1053/j.ajkd.2011.10.041. Epub 2011 Dec 9.
Results Reference
derived
Learn more about this trial
Vitamin K2 Supplementation to Activate Matrix Gla Protein (MGP) as Endogenous Inhibitor of Vascular Calcification in Hemodialysis Patients
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