Official Title: “Safety Study of Vitamin K2 During Anticoagulation in Human Volunteers”

Oral anticoagulants that are widely used for the treatment of thrombo-embolic disease exert their effect by blocking the recycling of vitamin K. Vitamin K acts as a co-factor in the posttranslational carboxylation of vitamin K-dependent proteins such as osteocalcin and matrix-gla protein. It is important to quantify the dose-response relationship of the interaction between vitamin K and oral anticoagulants and to investigate at what dosage vitamin K will interfere with oral anticoagulants in a clinically relevant way.

Study Type: Interventional

Study Design: Treatment, Open Label, Single Group Assignment, Safety/Efficacy Study

Study Primary Completion Date: December 2007

From all K-vitamins, menaquinone-7 has been identified as the most effective cofactor for the carboxylation reaction of Gla-proteins. In this respect it is important to quantify the dose-response relationship of the interaction between oral anticoagulants and menaquinone-7.

The primary objective of the study is to demonstrate at what menaquinone-7 intake the vitamin will interfere with oral anticoagulants in a clinically relevant way. Clinically relevant is defined as a decrease in level of anticoagulation that would require a change in oral anticoagulant treatment in order to stay within target levels. Secondary objective of the study is to investigate changes in carboxylation level of osteocalcin and matrix-gla protein after menaquinone-7 supplementation during the oral anticoagulation treatment period. This will demonstrate whether during oral anticoagulation menaquinone-7 will be transported preferentially to the liver or to other target tissues.

Intervention(s) in this Clinical Trial

• Drug: acenocoumarol
  • max 5 mg per day during 10 weeks
• Dietary Supplement: menaquinone-7
  • In successive weeks (6 weeks) the dosage is increased over the range 10 µg to 20 µg increasing to 45 µg MK-7 for the final week.

Primary Measures

• changes in level anticoagulation
  • Time Frame: 10 weeks
    Safety Issue?: No

Secondary Measures

• changes in carboxylation level of osteocalcin and matrix-gla protein
  • Time Frame: 10 weeks
    Safety Issue?: No

Inclusion Criteria:

• Healthy male and female adults between 18 and 45 years of age.
• Subjects of normal body weight and height according to BMI < 30
• Subject has given written consent to take part in the study

Exclusion Criteria:

• Subjects with (a history of) of coagulation disorders
• Subjects with (a history of) metabolic or gastrointestinal disease
• Subjects using (multi)-vitamin supplements containing vitamin K
• Subjects presenting chronic inflammatory diseases
• Subjects using any medication 3 months prior to the study (e.g. corticoϊd treatment, oral anticoagulants)
• Subjects using oral anticonception
• Subject with (a history of) soy allergy

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 45 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Maastricht University Medical Center

Overall Clinical Trial Officials and Contacts

Cees Vermeer, PhD Principal Investigator Maastricht University Medical Center  

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00512928

Study ID Number: MEC 07-3-032

ClinicalTrials.gov Identifier: NCT00512928

Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)