Dose-finding Study for Vitamin K2 in Human Volunteers

Study Overview
=================
Brief Summary
-----------------
Earlier studies have shown that high vitamin K-intake leads to improved bone and vascular health by increased carboxylation of Gla-proteins in these tissues. From all K-vitamins, Menaquinone-7 (MK7) has been identified as the most effective cofactor for the carboxylation reaction of Gla-proteins such as osteocalcin and matrix-gla protein. The question remains which dosage of MK7 leads to optimal carboxylation levels of these proteins. The primary objective of this double-blind randomized intervention study is to establish the optimal dose of MK7 for carboxylation of the vitamin K-dependent proteins osteocalcin in bone and matrix-gla protein in the vessel wall. The optimal dose will be the concentration at which osteocalcin and matrix-gla protein are > 90% in the active (=carboxylated) form.

Detailed Description
-----------------
This study is a double-blind randomized intervention study. In total 42 healthy volunteers (men and women) between 18 and 45 years will be recruited among the Maastricht University community (coworkers/students) and randomized into one of the following groups: Placebo, 10 mcg MK7, 20 mcg MK7, 45 mcg MK7, 90 mcg MK7, 180 mcg MK7, 360 mcg MK7. Each group will consist of 6 volunteers with approximately equal numbers of men and women (3 men / 3 women). A double-blind design of the study is chosen to avoid the occurrence of bias during the study. The randomization procedure will be performed by an investigator who is not involved in the coordination of the study and will generate specific randomization codes for each subject. After randomization, the volunteers consume the indicated amount of capsules once daily with either breakfast of dinner during a period of 12 weeks. During the first week, blood samples of the volunteers will be collected at day 0, 1, 3 and 7 to study immediate effects on carboxylation of OC and MGP. After the first week, blood samples will be drawn every first day of week 2, 4, 6, 8, 10, and 12.

Official Title
-----------------
Dose-finding Study for Vitamin K2 in Human Volunteers

Conditions
-----------------
Vitamin K-status

Intervention / Treatment
-----------------
* Dietary Supplement: Placebo
* Dietary Supplement: MK7


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) metabolic or gastrointestinal disease Subject with (a history of) soy allergy Subjects using vitamin supplements containing vitamin K Subjects presenting chronic inflammatory diseases Subjects receiving systemic treatment or topical treatment likely to interfere with evaluation of the study parameters Subjects receiving corticoϊd treatment Subjects using oral anticoagulants

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: PLACEBO<br>MK7 dosage 0 mcg, 4 capsules, orally, daily for 12 weeks. | Dietary Supplement: Placebo<br> <br> |
| Active Comparator: MK7_10<br>MK7 dosage 10 mcg, 1 capsule of 10 mcg and 3 placebo-capsules, orally, daily for 12 weeks. | Dietary Supplement: MK7<br> <br> * Other names: Menaquinone-7;|
| Active Comparator: MK7_20<br>MK7 dosage 20 mcg, 2 capsules of 10 mcg and 2 placebo-capsules, orally, daily for 12 weeks. | Dietary Supplement: MK7<br> <br> * Other names: Menaquinone-7;|
| Active Comparator: MK7_45<br>MK7 dosage 45 mcg, 1 capsules of 45 mcg and 3 placebo-capsules, orally, daily for 12 weeks. | Dietary Supplement: MK7<br> <br> * Other names: Menaquinone-7;|
| Active Comparator: MK7_90<br>MK7 dosage 90 mcg, 2 capsules of 45 mcg and 2 placebo-capsules, orally, daily for 12 weeks. | Dietary Supplement: MK7<br> <br> * Other names: Menaquinone-7;|
| Active Comparator: MK7_180<br>MK7 dosage 180 mcg, 4 capsules of 45 mcg, orally, daily for 12 weeks. | Dietary Supplement: MK7<br> <br> * Other names: Menaquinone-7;|
| Active Comparator: MK7_360<br>MK7 dosage 360 mcg, 1 capsule of 360 mcg and 3 placebo-capsules, orally, daily for 12 weeks. | Dietary Supplement: MK7<br> <br> * Other names: Menaquinone-7;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| undercarboxylated osteocalcin (ucOC) | UcOC will be assessed by making use of a sandwich ELISA (in ng/ml) | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| carboxylated osteocalcin (cOC) | cOC will be assessed by making use of a sandwich ELISA (in ng/ml) | 12 weeks | 
| undercarboxylated matrix-gla protein (ucMGP) | ucMGP will be assessed by making use of a sandwich ELISA (in pM) | 12 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
vitamin K2, dosis-response, osteocalcin, matrix-gla protein