This trial is active, not recruiting.

Condition vascular stiffness
Treatments menaquinone-7, placebo
Sponsor Maastricht University Medical Center
Start date June 2015
End date September 2017
Trial size 240 participants
Trial identifier NCT02404519, METC143058


Vitamin K is required for the activation of the inhibitor of vascular calcification: Matrix Gla Protein (MGP). In an earlier study the beneficial effect of menaquinone-7 (MK-7), a vitamin K2 form, was observed on the stiffness of the vessel wall in postmenopausal women. It decreased the circulating form of inactive MGP and improved the vascular elasticity (local) and aortic pulse wave velocity (regional). The decrease of circulating inactive MGP was observed after 2-3 months MK-7 supplementation and the effect of MK-7 on the clinical endpoints was observed within 3 years of supplementation. It is demonstrated in several studies that cardiovascular risk increases with decreasing vitamin K intake and increasing levels of inactive MGP. In this study the investigators select subjects in the highest tertile of circulating inactive MGP. This study group will consist of subjects with increased cardiovascular risk and it is expected that effects of MK-7 on clinical endpoints in this group will be measurable within 1 year of supplementation.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose prevention
(Active Comparator)
Menaquinone-7 180 microgram tablet, by mouth, daily for 1 year
menaquinone-7 MK-7
1 tablet containing 180 micrograms MK-7 taken orally every day during 1 year
(Placebo Comparator)
Placebo tablet, by mouth, daily for 1 year
1 tablet without MK-7 taken orally every day during 1 year

Primary Outcomes

carotid-femoral Pulse Wave Velocity
time frame: baseline and 1 year

Secondary Outcomes

Elasticity of the common carotid artery
time frame: baseline and 1 year
circulating inactive Matrix Gla Protein (MGP)
time frame: baseline and 1 year

Eligibility Criteria

Male or female participants from 40 years up to 70 years old.

Inclusion Criteria: - Men and women between 40 and 70 years old - Subjects with body weight and height according to BMI between 20 and 35 kg/m2 - Subjects of Caucasian race - Subject has given written consent to take part in the study - Subjects with circulating dp-ucMGP higher than 500 pmol/L Exclusion Criteria: - Subjects with cardiovascular disease - Subjects with hyperlipidaemia - Subjects with (a history of) metabolic or gastrointestinal disease - Subjects presenting chronic degenerative and/or inflammatory disease - Use of more than 3 units alcohol/day - Subjects receiving oestrogen treatment (women) - Subjects using corticosteroids - Subjects using oral anticoagulants and subjects with clotting disorders - Subjects using vitamin K containing multivitamins or supplements

Additional Information

Official title Intervention Study on the Effect of Vitamin K2 (Menaquinone-7) Supplementation on the Vascular Stiffness in Subjects With Poor Vitamin K-status
Principal investigator Marjo HJ Knapen, BSc
Description This study will be a double-blind randomized placebo-controlled intervention study. In total 240 healthy men and women between 40 and 70 years will be recruited in the province of Limburg through small advertisements in local newspapers. Eligible participants will be randomized into 2 study groups: - Group 1: MK-7 (1 tablet: MK-7 dosage is 180 μg) - Group 2: Placebo (1 tablet: MK-7 dosage is 0 µg) Each group will consist of 120 participants. A double-blind design is chosen to avoid the occurrence of bias during the study. After randomization, the participants consume the placebo or MK-7 tablets once daily with either breakfast or dinner during one year. People who are interested to participate will come to the research laboratory of VitaK for a screening visit (day -14). During this visit, the investigator will check whether the volunteers are eligible for inclusion based on the in- and exclusion criteria. After meeting the inclusion criteria and none of the exclusion criteria, volunteers will be assigned a randomization number from a computer-generated randomization list. A stratified block randomization will be performed for gender, in order to avoid unequal distribution of men and women among the 2 treatment groups. On-site measurements will be performed at t=0 and after 1 year of treatment: the carotid-femoral Pulse Wave Velocity (cfPWV; primary outcome) and echotracking of the common carotid artery to assess the vascular stiffness (secondary outcome). A Whole Body scan with DXA will be performed to determine total fat and lean mass of the participants. Blood will be taken after an overnight fasting period at t=0 and after 1 year to measure the circulating level of inactive MGP. Results from our previous study (NCT00642551) showed significant changes in vascular characteristics, pulse wave velocity after a 3 year intervention period with a daily dosage of 180 µg MK-7 in 240 postmenopausal women. After 1 year MK-7 intervention inactive MGP levels (improvement of vascular vitamin K status) were decreased 50% compared to placebo and remained at this level during the following 2 years of intervention. Recently published population-based studies show that the unfavorable cardiovascular outcomes are mainly attributable to those within the highest quartile of circulating dp-ucMGP. We expect, therefore, that an intervention study among preselected subjects with poor vascular vitamin K status (inactive MGP levels > 500 pmol/L) and treatment with the same dosage MK-7 (i.e. 180 µg/day) during one year will have a more pronounced effect on arterial stiffening and pulse wave velocity.
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Maastricht University Medical Center.