Vascular StiffnessNCT02404519
Vitamin K2 Effect on Vascular Stiffening in Subjects With a Poor Vitamin K-status
A study testing Menaquinone-7 in people with Vascular Stiffness, run by Maastricht University Medical Center.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 40 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Vascular Stiffness
- What is being tested?
- Menaquinone-7
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 240 participants
- Where
- No sites listed yet
- Study dates
- Jan 2016to Sep 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 9Show fewer
- Subjects using corticosteroids
- Subjects using oral anticoagulants and subjects with clotting disorders
- Subjects using vitamin K containing multivitamins or supplements
About this study
Official title: Intervention Study on the Effect of Vitamin K2 (Menaquinone-7) Supplementation on the Vascular Stiffness in Subjects With Poor Vitamin K-status
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.
Read the detailed 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 > 400 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.
The follow-up study will be performed at the end of the intervention period of 1 year, with participants who have completed the one year intervention study. From this study population eligible participants (men and women) will be selected. In total 100 participants will be invited. Measurements will be performed at the same day: the carotid-femoral Pulse Wave Velocity (cfPWV), echotracking of the common carotid artery to assess the vascular stiffness and accelerated plethysmography measurements (APG) will be assessed using an fingertip oximeter StiffnoGraph (Taiwan): heart rate, SpO2 (oxygen saturation) and stiffness score.
- Conditions
- Vascular Stiffness
- Being tested
- Menaquinone-7, Placebo
- Keywords
- Vitamin K, Menaquinone-7, Matrix Gla Protein, Vascular stiffness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Menaquinone-7Dietary supplement
Also called MK-7
1 tablet containing 180 micrograms MK-7 taken orally every day during 1 year
PlaceboDietary supplement
1 tablet without MK-7 taken orally every day during 1 year
| Study group | Role | What they receive |
|---|---|---|
| Menaquinone-7 | Active comparator | Menaquinone-7 180 microgram tablet, by mouth, daily for 1 year Receives: Dietary Supplement: Menaquinone-7 |
| Placebo | Placebo comparator | Placebo tablet, by mouth, daily for 1 year Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline carotid-femoral Pulse Wave Velocity (PWV) at 1 year
PWV (in m/s) will be assessed noninvasively by measuring carotid-femoral PWV, using mechanotransducers applied directly on the skin.
Measured: 1 year
Secondary outcomes (8)
Change from baseline diameter of the common carotid artery at 1 year
The diameter of the common carotid artery will be measured using a linear array transducer connected to an ultrasound scanner. The diameter will be assessed in mm.
Measured: 1 year
Diameter of the common carotid artery
The diameter of the common carotid artery will be measured using a linear array transducer connected to an ultrasound scanner. The diameter will be assessed in mm.
Measured: up to 1 year post-intervention
Change from baseline distension of the common carotid artery at 1 year
The distension of the common carotid artery will be measured using a linear array transducer connected to an ultrasound scanner. The distension will be assessed in micrometer.
Measured: 1 year
Distension of the common carotid artery
The distension of the common carotid artery will be measured using a linear array transducer connected to an ultrasound scanner. The distension will be assessed in micrometer.
Measured: up to 1 year post-intervention
Change from baseline intima-media thickness (IMT) of the common carotid artery at 1 year
The IMT of the common carotid artery will be measured using a linear array transducer connected to an ultrasound scanner. The IMT will be assessed in micrometer.
Measured: 1 year
Intima-media thickness (IMT) of the common carotid artery
The IMT of the common carotid artery will be measured using a linear array transducer connected to an ultrasound scanner. The IMT will be assessed in micrometer.
Measured: up to 1 year post-intervention
circulating inactive Matrix Gla Protein (dp-ucMGP)
Dp-ucMGP (in pM) will be measured using a sandwich ELISA, based on monoclonal antibodies.
Measured: baseline and 1 year
carotid-femoral Pulse Wave Velocity (PWV)
PWV (in m/s) will be assessed noninvasively by measuring carotid-femoral PWV, using mechanotransducers applied directly on the skin.
Measured: up to 1 year post-intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2015 (estimated)
- Study startJan 2016
- Primary completionSep 2017
- Study completionSep 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Vascular StiffnessStudies of the same condition, open and under way.
- More trials run by Maastricht University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 240 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Marjo Knapen, Maastricht University Medical Center
- Investigators
- Marjo HJ Knapen, BSc, Principal investigator, VitaK BV/Maastricht University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02404519
- Sponsor's protocol ID
- METC143058
- Status last verified
- Apr 2018
- First submitted
- 23 Mar 2015
- Last updated
- 30 Apr 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intervention Study on the Effect of Vitamin K2 (Menaquinone-7) Supplementation on the Vascular Stiffness in Subjects With Poor Vitamin K-status
- ClinicalTrials.gov ID
- NCT02404519
- Acronym / sponsor ID
- METC143058
- Conditions
- Vascular Stiffness
- Keywords
- Vitamin K, Menaquinone-7, Matrix Gla Protein, Vascular stiffness
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 240 participants (actual)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Study start
- Jan 2016 (actual)
- Primary completion
- Sep 2017 (actual)
- Study completion
- Sep 2018 (estimated)
- First posted
- 31 Mar 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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 > 400 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.
The follow-up study will be performed at the end of the intervention period of 1 year, with participants who have completed the one year intervention study. From this study population eligible participants (men and women) will be selected. In total 100 participants will be invited. Measurements will be performed at the same day: the carotid-femoral Pulse Wave Velocity (cfPWV), echotracking of the common carotid artery to assess the vascular stiffness and accelerated plethysmography measurements (APG) will be assessed using an fingertip oximeter StiffnoGraph (Taiwan): heart rate, SpO2 (oxygen saturation) and stiffness score.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Menaquinone-7 | Active comparator | Dietary Supplement: Menaquinone-7Menaquinone-7 180 microgram tablet, by mouth, daily for 1 year |
| Placebo | Placebo comparator | Dietary Supplement: PlaceboPlacebo tablet, by mouth, daily for 1 year |
Who may qualify
- Ages
- 40 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Menaquinone-7Also: MK-71 tablet containing 180 micrograms MK-7 taken orally every day during 1 year | Dietary supplement | Menaquinone-7 |
| Placebo1 tablet without MK-7 taken orally every day during 1 year | Dietary supplement | Placebo |
Primary outcome
Change from baseline carotid-femoral Pulse Wave Velocity (PWV) at 1 year
Time frame: 1 year
PWV (in m/s) will be assessed noninvasively by measuring carotid-femoral PWV, using mechanotransducers applied directly on the skin.
8 secondary outcomes
Change from baseline diameter of the common carotid artery at 1 year
Time frame: 1 year
Diameter of the common carotid artery
Time frame: up to 1 year post-intervention
Change from baseline distension of the common carotid artery at 1 year
Time frame: 1 year
Distension of the common carotid artery
Time frame: up to 1 year post-intervention
Change from baseline intima-media thickness (IMT) of the common carotid artery at 1 year
Time frame: 1 year
Intima-media thickness (IMT) of the common carotid artery
Time frame: up to 1 year post-intervention
circulating inactive Matrix Gla Protein (dp-ucMGP)
Time frame: baseline and 1 year
carotid-femoral Pulse Wave Velocity (PWV)
Time frame: up to 1 year post-intervention
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marjo HJ Knapen, BSc principal investigator
VitaK BV/Maastricht University
Questions about this trial
What is this clinical trial studying?
A study testing Menaquinone-7 in people with Vascular Stiffness, run by Maastricht University Medical Center.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline carotid-femoral Pulse Wave Velocity (PWV) at 1 year (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Apr 2018.