Vitamin K2 Supplementation to Activate Matrix Gla Protein (MGP) as Endogenous Inhibitor of Vascular Calcification in Hemodialysis Patients

NCT01407601 | Completed Phase 3

• 1 other identifier: EK 111/07
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 3

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).

Conditions

CKD 5D, Hemodialysis

Keywords

vitamin K; MK-7; Hemodialysis; vascular calcification; Matrix Gla protein; Osteocalcin

Outcome Measures

Primary Outcomes (3)

• 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.

  after 6 weeks of supplementation

• 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.

  after 6 weeks of supplementation

• 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.

  after 6 weeks of supplementation

Secondary Outcomes (2)

• increase of plasma levels of carboxylated MGP

  after 6 weeks of supplementation

• increase of plasma levels of carboxylated osteocalcin

  after 6 weeks of supplementation

Study Arms (3)

45 µg MK-7

EXPERIMENTAL

45 µg MK-7 daily over 6 weeks

Dietary Supplement: daily supplementation of MK-7 over 6 weeks

135 µg MK-7

EXPERIMENTAL

135 µg MK-7 daily over 6 weeks

Dietary Supplement: daily supplementation of MK-7 over 6 weeks

360 µg MK-7

EXPERIMENTAL

360 µg MK-7 daily over 6 weeks

Dietary Supplement: daily supplementation of MK-7 over 6 weeks

Interventions

daily supplementation of MK-7 over 6 weeks DIETARY_SUPPLEMENT

once daily intake of MK-7 prior to dialysis over 6 weeks

135 µg MK-7; 360 µg MK-7; 45 µg MK-7

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \> 18 years of age
• minimum of 3 months of hemodialysis
• written consent

You may not qualify if:

• 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

Sponsors & Collaborators

• RWTH Aachen University: lead

Study Sites (3)

KfH Dialysis Unit Aachen

Aachen, North Rhine-Westphalia, 52074, Germany

Location

University Hospital of the RWTH Aachen

Aachen, North Rhine-Westphalia, 52074, Germany

Location

Dialysis Unit Erkelenz

Erkelenz, North Rhine-Westphalia, 41812, Germany

Location

Related Publications (1)

• 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.

  PMID: 22169620 DERIVED

MeSH Terms

Conditions

Vascular Calcification

Condition Hierarchy (Ancestors)

Calcinosis; Calcium Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Ralf Westenfeld, MD

  University Clinic of the RWTH Aachen

  PRINCIPAL INVESTIGATOR

• Georg Schlieper, MD

  University Clinic of the RWTH Aachen

  STUDY CHAIR

• Stefan Holzmann, MD

  Dialysis Unit Erkelenz, Germany

  STUDY CHAIR

• Stephan Heidenreich, MD

  KfH Dialysis Centre Aachen, Schurzelter Strasse

  STUDY CHAIR

• Juergen Floege, MD

  University Clinic of the RWTH Aachen

  STUDY DIRECTOR

• Thilo Krueger, MD

  University Hospital of the RWTH Aachen

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: July 29, 2011
• First Posted: August 2, 2011
• Study Start: January 1, 2008
• Primary Completion: May 1, 2008
• Study Completion: July 1, 2009
• Last Updated: August 2, 2011

Record last verified: 2011-08

Locations

DE (3)