Intervention Study on the Effect of Vitamin K2 (Menaquinone-7) Supplementation on the Vascular Stiffness in Subjects With Poor Vitamin K-status
试验速览
- 阶段
- 不适用
- 入组人数
- 240
- 主要终点
- Change from baseline carotid-femoral Pulse Wave Velocity (PWV) at 1 year
研究概览
简要总结
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.
Vascular stiffness can be determined with different techniques. The vascular characteristics determined with Pulse Wave Velocity (PWV), ultrasound of the common carotid artery and accelerated plethysmography (APG) with a fingertip device will be compared in a follow-up study.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 40 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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 400 pmol/L
排除标准
- •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
研究组 & 干预措施
Placebo
Placebo tablet, by mouth, daily for 1 year
干预措施: Placebo (Dietary Supplement)
Menaquinone-7
Menaquinone-7 180 microgram tablet, by mouth, daily for 1 year
干预措施: Menaquinone-7 (Dietary Supplement)
结局指标
主要结局
Change from baseline carotid-femoral Pulse Wave Velocity (PWV) at 1 year
时间窗: 1 year
PWV (in m/s) will be assessed noninvasively by measuring carotid-femoral PWV, using mechanotransducers applied directly on the skin.
次要结局
- Change from baseline diameter of the common carotid artery at 1 year(1 year)
- carotid-femoral Pulse Wave Velocity (PWV)(up to 1 year post-intervention)
- Change from baseline distension of the common carotid artery at 1 year(1 year)
- Distension of the common carotid artery(up to 1 year post-intervention)
- Diameter of the common carotid artery(up to 1 year post-intervention)
- Change from baseline intima-media thickness (IMT) of the common carotid artery at 1 year(1 year)
- Intima-media thickness (IMT) of the common carotid artery(up to 1 year post-intervention)
- circulating inactive Matrix Gla Protein (dp-ucMGP)(baseline and 1 year)
研究者
Marjo Knapen
Marjo Knapen, BSc
Maastricht University Medical Center