Coronary Artery CalcificationInterVitaminKNCT05259046
The InterVitaminK Trial - Effects of Vitamin K Supplementation on Cardiovascular, Metabolic, and Bone Health
A study testing Menaquinone-7 (MK-7) tablet (333 µg) in people with Coronary Artery Calcification and Arterial Stiffness, run by Bispebjerg Hospital at 1 site in Denmark.
Trial summary
The purpose of this study is to examine the effect of menaquinone-7 (MK-7) supplementation on cardiovascular, metabolic, and bone health. Read more about this study
- Who is it for?
- Ages 50 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Coronary Artery Calcification, Arterial Stiffness
- What is being tested?
- Menaquinone-7 (MK-7) tablet (333 µg)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 450 participants
- Where
- 1 siteDenmark
- Study dates
- 21 Jun 2022to 28 Feb 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 50 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Detectable CAC (Agatson score >=10) assessed by Cardiac Computed Tomography (CT) scan in the Inter99 20-year follow-up study
Who cannot join
- Manifest CVD (prior cerebral infarct, prior myocardial infarct, prior percutaneous coronary intervention or prior coronary artery bypass surgery)
- Noise on the CT scan, which complicates an accurate assessment of CAC and interpretation of the CT scan. An example is a pacemaker
- Current treatment with Vitamin K antagonist (VKA).
- History of coagulation disorders (hemophilia, von Willebrand disease, sickle cell anemia)
- Active malignant disease (ongoing treatment)
- Previous surgical removal of the thyroid gland, or one or more of the parathyroid glands
- Regular use of vitamin K supplements other than trial tablets
- Pregnancy or breastfeeding
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Center for Clinical Research and Prevention
Copenhagen, Glostrup, DK-2600
About this study
Official title: Novel Health Effects of Vitamin K: a Placebo-controlled Randomized Trial in the General Population (InterVitaminK)
The purpose of this study is to examine the effect of menaquinone-7 (MK-7) supplementation on cardiovascular, metabolic, and bone health.
Read the detailed description
Background: Research suggest that vitamin K may have protective effects against non-communicable and age-related diseases as diverse as cardiovascular disease (CVD), osteoporosis, and type 2 diabetes (T2D). However, there is a need for larger studies investigating the potential health effects of vitamin K in the general population.
Objective: The objective of the InterVitaminK trial is to investigate the effects of vitamin K (menaquinone-7, MK-7) supplementation on cardiovascular, metabolic, and bone health.
Hypothesis: The primary hypothesis is that vitamin K supplementation will reduce the progression of coronary artery calcification (CAC) with 15% compared with placebo.
Methods: The InterVitaminK trial is a double-blinded, placebo-controlled, randomized intervention trial. The trial will be conducted in Denmark at the Center for Clinical Research and Prevention and the CT scans will be performed at Rigshospitalet, Denmark. Participants from the Inter99 cohort with detectable CAC (Agatson score >=10) are eligible for the trial. Participants will be randomized 1:1 to receive one daily tablet with MK-7 or placebo for a period of 3 years. Randomization is done in blocks of 6 using computer generated random numbers. Participants are invited for a health examination at baseline and after 1, 2, and 3 years intervention. CT scans are performed at baseline and at 3-year follow-up.
Outcomes: The primary study outcome is progression of CAC from baseline to 3-year follow-up, assessed by Cardiac CT scans. Secondary outcomes are bone mineral density, pulmonary function, and biomarkers of insulin resistance.
Power: Power calculation and sample size considerations are based on the primary endpoint (three-year progression in CAC). A total of 450 participants will be enrolled in the trial. Based on a previous vitamin K trial and data from the Danish cohort study DANCAVAS, it is assumed that the geometric mean three-year progression in CAC in the control group participants is 3.0 with an SD of 1.3. The hypothesis is that vitamin K supplementation can reduce the three-year progression in CAC by 15%. With an estimated dropout-rate of 25% during the study period, a total of 450 participants (225 participants in each group) enrolled at baseline, will provide 89% power to demonstrate an effect of at least 15% (alpha 0.05).
Statistical analyses: The effect of vitamin K supplementation on the primary outcome (CAC) will be analyzed using mixed effects linear regression. The mixed effects linear regression will include a fixed effect for group allocation (intervention/control), a fixed effect for time point (baseline and 3-year follow-up), fixed effect for baseline CAC score and an interaction between group allocation and time point. As baseline measurements are conducted prior to enrolment, treatment at baseline will be modelled as a common treatment category, constraining baseline measurements to no systematic treatment effect between the two arms. The mixed effects model will include a random intercept for each enrolled participant and a first order autoregressive correlation structure allowing correction of measurement for the same participant with higher correlation for measurements closer in time.
Likewise, secondary outcomes and supportive outcomes will be analyzed using mixed effects linear regression. Analysis and presentation of data will be in accordance with the CONSORT guidelines. For details, see the statistical analysis plan uploaded at clinicaltrials.gov (NCT05259046).
- Conditions
- Coronary Artery Calcification, Arterial Stiffness
- Being tested
- Menaquinone-7 (MK-7) tablet (333 µg), Placebo tablet
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Menaquinone-7 (MK-7) tablet (333 µg)Dietary supplement
One MK-7 tablet containing 333 µg MK-7 per day
Placebo tabletDietary supplement
One placebo tablet per day
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Experimental | Intervention treatment . Dietary supplementation with Menaquinone-7 (MK-7) tablet (333 µg/day). MK-7 (K2VITAL®DELTA) tablets are manufactured by Kappa Bioscience AS, Oslo, Norway. Receives: Dietary Supplement: Menaquinone-7 (MK-7) tablet (333 µg) |
| Placebo | Placebo comparator | Placebo tablet (no active treatment). The placebo tablets will match the intervention treatment in both taste and appearance. Placebo tablets are manufactured by Kappa Bioscience AS, Oslo, Norway. Receives: Dietary Supplement: Placebo tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total coronary artery calcification
Total coronary artery calcification score (unit: Agatston score) in the coronary arteries, assessed by non-contrast Cardiac CT scans. A high score reflects higher degree of calcification in the coronary arteries and increased risk of coronary artery disease. The outcome will be evaluated by randomization group (active versus placebo).
Measured: Baseline to three years of follow-up
Secondary outcomes (7)
Coronary plaque composition
Total coronary plaque composition (calcified, non-calcified subcomponents) assessed by contrast Cardiac CT scans (unit: cubic millimeters)
Measured: Baseline to three years of follow-up
Arterial stiffness
Arterial stiffness assessed by carotid-femoral pulse wave velocity examination (unit: meters/second)
Measured: Baseline to three years of follow-up
Blood pressure
Blood pressure (unit: millimeter of mercury) assessed by a digital blood pressure device. Both systolic and diastolic blood pressure will be evaluated.
Measured: Baseline to three years of follow-up
Aortic valve calcifications
Aortic valve calcifications assessed by non-contrast Cardiac CT scans (unit: Agatston score). A high score reflects higher degree of calcification
Measured: Baseline to three years of follow-up
Bone mineral density
Bone mineral density assessed by quantitative CT scan of the columna thoracalis (unit: milligrams/cubic centimeter)
Measured: Baseline to three years of follow-up
Pulmonary function
Pulmonary function reflected by forced expiratory volume in one second (FEV1) (unit: Volume in Liter)
Measured: Baseline to three years of follow-up
Insulin resistance
Insulin resistance assessed by Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (unit: millimoles/liter * picomoles/liter)
Measured: Baseline to three years of follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2022
- Study start21 Jun 2022
- Primary completion30 Jan 2027 (estimated)
- Study completion28 Feb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery CalcificationStudies of the same condition, open and under way.
- 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
- Model description
- Participants will be randomized in a double-blinded manner 1:1 to MK-7 tablets or placebo tablets. Randomisation is conducted in blocks of 6 using computer generated random numbers. A total of 450 participants will be enrolled (225 in each group).
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 450 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bispebjerg Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Allan Linneberg, Bispebjerg Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05259046
- Sponsor's protocol ID
- InterVitaminK
- Acronym
- InterVitaminK
- Status last verified
- Feb 2026
- First submitted
- 7 Jan 2022
- Last updated
- 17 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: After the publication of the main results upon completion of the trial, data will be available on a collaborative basis following approval from the InterVitaminK Trial Steering Committee and the regional data protection authority.
Publications
Kampmann FB, Thysen SM, Nielsen CFB, Kofoed KF, Kober L, Pham MHC, Vaag A, Jorgensen NR, Petersen J, Jacobsen RK, Karhus LL, Diederichsen A, Frimodt-Moller M, Linneberg A. Study protocol of the InterVitaminK trial: a Danish population-based randomised double-blinded placebo-controlled trial of the effects of vitamin K (menaquinone-7) supplementation on cardiovascular, metabolic and bone health. BMJ Open. 2023 May 19;13(5):e071885. doi: 10.1136/bmjopen-2023-071885.
PubMed 37208133
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Novel Health Effects of Vitamin K: a Placebo-controlled Randomized Trial in the General Population (InterVitaminK)
- ClinicalTrials.gov ID
- NCT05259046
- Acronym / sponsor ID
- InterVitaminK / InterVitaminK
- Conditions
- Coronary Artery Calcification, Arterial Stiffness
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 450 participants (actual)
- Lead sponsor
- Bispebjerg HospitalUniversity, hospital or other
- Study start
- 21 Jun 2022 (actual)
- Primary completion
- 30 Jan 2027 (estimated)
- Study completion
- 28 Feb 2027 (estimated)
- First posted
- 28 Feb 2022 (actual)
- 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.
The purpose of this study is to examine the effect of menaquinone-7 (MK-7) supplementation on cardiovascular, metabolic, and bone health.
Detailed description
Background: Research suggest that vitamin K may have protective effects against non-communicable and age-related diseases as diverse as cardiovascular disease (CVD), osteoporosis, and type 2 diabetes (T2D). However, there is a need for larger studies investigating the potential health effects of vitamin K in the general population.
Objective: The objective of the InterVitaminK trial is to investigate the effects of vitamin K (menaquinone-7, MK-7) supplementation on cardiovascular, metabolic, and bone health.
Hypothesis: The primary hypothesis is that vitamin K supplementation will reduce the progression of coronary artery calcification (CAC) with 15% compared with placebo.
Methods: The InterVitaminK trial is a double-blinded, placebo-controlled, randomized intervention trial. The trial will be conducted in Denmark at the Center for Clinical Research and Prevention and the CT scans will be performed at Rigshospitalet, Denmark. Participants from the Inter99 cohort with detectable CAC (Agatson score >=10) are eligible for the trial. Participants will be randomized 1:1 to receive one daily tablet with MK-7 or placebo for a period of 3 years. Randomization is done in blocks of 6 using computer generated random numbers. Participants are invited for a health examination at baseline and after 1, 2, and 3 years intervention. CT scans are performed at baseline and at 3-year follow-up.
Outcomes: The primary study outcome is progression of CAC from baseline to 3-year follow-up, assessed by Cardiac CT scans. Secondary outcomes are bone mineral density, pulmonary function, and biomarkers of insulin resistance.
Power: Power calculation and sample size considerations are based on the primary endpoint (three-year progression in CAC). A total of 450 participants will be enrolled in the trial. Based on a previous vitamin K trial and data from the Danish cohort study DANCAVAS, it is assumed that the geometric mean three-year progression in CAC in the control group participants is 3.0 with an SD of 1.3. The hypothesis is that vitamin K supplementation can reduce the three-year progression in CAC by 15%. With an estimated dropout-rate of 25% during the study period, a total of 450 participants (225 participants in each group) enrolled at baseline, will provide 89% power to demonstrate an effect of at least 15% (alpha 0.05).
Statistical analyses: The effect of vitamin K supplementation on the primary outcome (CAC) will be analyzed using mixed effects linear regression. The mixed effects linear regression will include a fixed effect for group allocation (intervention/control), a fixed effect for time point (baseline and 3-year follow-up), fixed effect for baseline CAC score and an interaction between group allocation and time point. As baseline measurements are conducted prior to enrolment, treatment at baseline will be modelled as a common treatment category, constraining baseline measurements to no systematic treatment effect between the two arms. The mixed effects model will include a random intercept for each enrolled participant and a first order autoregressive correlation structure allowing correction of measurement for the same participant with higher correlation for measurements closer in time.
Likewise, secondary outcomes and supportive outcomes will be analyzed using mixed effects linear regression. Analysis and presentation of data will be in accordance with the CONSORT guidelines. For details, see the statistical analysis plan uploaded at clinicaltrials.gov (NCT05259046).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Participants will be randomized in a double-blinded manner 1:1 to MK-7 tablets or placebo tablets. Randomisation is conducted in blocks of 6 using computer generated random numbers. A total of 450 participants will be enrolled (225 in each group).
| Arm | Type | Receives |
|---|---|---|
| Intervention | Experimental | Dietary Supplement: Menaquinone-7 (MK-7) tablet (333 µg)Intervention treatment . Dietary supplementation with Menaquinone-7 (MK-7) tablet (333 µg/day). MK-7 (K2VITAL®DELTA) tablets are manufactured by Kappa Bioscience AS, Oslo, Norway. |
| Placebo | Placebo comparator | Dietary Supplement: Placebo tabletPlacebo tablet (no active treatment). The placebo tablets will match the intervention treatment in both taste and appearance. Placebo tablets are manufactured by Kappa Bioscience AS, Oslo, Norway. |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Detectable CAC (Agatson score >=10) assessed by Cardiac Computed Tomography (CT) scan in the Inter99 20-year follow-up study
Key exclusion criteria (8 listed)
- Manifest CVD (prior cerebral infarct, prior myocardial infarct, prior percutaneous coronary intervention or prior coronary artery bypass surgery)
- Noise on the CT scan, which complicates an accurate assessment of CAC and interpretation of the CT scan. An example is a pacemaker
- Current treatment with Vitamin K antagonist (VKA).
- History of coagulation disorders (hemophilia, von Willebrand disease, sickle cell anemia)
- Active malignant disease (ongoing treatment)
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-7 (MK-7) tablet (333 µg)One MK-7 tablet containing 333 µg MK-7 per day | Dietary supplement | Intervention |
| Placebo tabletOne placebo tablet per day | Dietary supplement | Placebo |
Primary outcome
Total coronary artery calcification
Time frame: Baseline to three years of follow-up
Total coronary artery calcification score (unit: Agatston score) in the coronary arteries, assessed by non-contrast Cardiac CT scans. A high score reflects higher degree of calcification in the coronary arteries and increased risk of coronary artery disease. The outcome will be evaluated by randomization group (active versus placebo).
7 secondary outcomes
Coronary plaque composition
Time frame: Baseline to three years of follow-up
Arterial stiffness
Time frame: Baseline to three years of follow-up
Blood pressure
Time frame: Baseline to three years of follow-up
Aortic valve calcifications
Time frame: Baseline to three years of follow-up
Bone mineral density
Time frame: Baseline to three years of follow-up
Pulmonary function
Time frame: Baseline to three years of follow-up
Insulin resistance
Time frame: Baseline to three years of follow-up
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2026.
- Derived from this study: PubMed 37208133Kampmann FB, Thysen SM, Nielsen CFB, Kofoed KF, Kober L, Pham MHC, Vaag A, Jorgensen NR, Petersen J, Jacobsen RK, Karhus LL, Diederichsen A, Frimodt-Moller M, Linneberg A. Study protocol of the InterVitaminK trial: a Danish population-based randomised double-blinded placebo-controlled trial of the effects of vitamin K (menaquinone-7) supplementation on cardiovascular, metabolic and bone health. BMJ Open. 2023 May 19;13(5):e071885. doi: 10.1136/bmjopen-2023-071885.
- Individual participant dataSharing planned: No. After the publication of the main results upon completion of the trial, data will be available on a collaborative basis following approval from the InterVitaminK Trial Steering Committee and the regional data protection authority.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Menaquinone-7 (MK-7) tablet (333 µg) in people with Coronary Artery Calcification and Arterial Stiffness, run by Bispebjerg Hospital at 1 site in Denmark.
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 1 inclusion and 8 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: under way, not looking for participants, as of the sponsor's last update on 17 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
This study is still under way. Results are not available in the source record yet.
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?
Total coronary artery calcification (time frame: Baseline to three years of follow-up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05259046, which also lists 1 linked publication.
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 17 Feb 2026.