Safety Study of Vitamin K2 During Anticoagulation in Human Volunteers

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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.

Official Title
-----------------
Safety Study of Vitamin K2 During Anticoagulation in Human Volunteers

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: acenocoumarol
* Dietary Supplement: menaquinone-7


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|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.|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in level anticoagulation |  | 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in carboxylation level of osteocalcin and matrix-gla protein |  | 10 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
vitamin K2, oral anticoagulation, interference, level of anticoagulation, carboxylation level of osteocalcin and matrix-gla protein