Vitamin K StatusNCT04450212
Vitamin K Supplementation Study in Healthy Volunteers (Aim 2B)
A study testing Phase I, Buccal Swab Collection for DNA Isolation and Phase II, Vitamin K (Vitacost) Supplementation in people with Vitamin K Status, run by University of Washington at 1 site in United States.
Trial summary
The overall purpose of this study is to determine how variation in the CYP4F2 gene modulates the synthesis of vitamin K-dependent clotting factors. We propose that the CYP4F2*3 gene variant increases short- and long-term vitamin K concentrations in the liver by reducing the efficiency of vitamin K metabolism. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Vitamin K Status
- What is being tested?
- Phase I, Buccal Swab Collection for DNA Isolation and Phase II, Vitamin K (Vitacost) Supplementation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 106 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Aug 2017to 31 Jul 2023
- 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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Participants will be males or females 18 years and older.
- Participants must read and understand English.
- Participants must be able to provide informed consent.
- Women not currently pregnant or lactating.
Who cannot join
- Participants less than 18 years of age.
- Participants unable to read and understand English.
- Participants unable to provide informed consent.
- Women who are pregnant or lactating.
Trial locations and contacts
1 site in 1 country.
About this study
The overall purpose of this study is to determine how variation in the CYP4F2 gene modulates the synthesis of vitamin K-dependent clotting factors. We propose that the CYP4F2*3 gene variant increases short- and long-term vitamin K concentrations in the liver by reducing the efficiency of vitamin K metabolism. The investigators will study the effect of vitamin K supplementation on two biomarkers of hepatic vitamin K concentration in groups with defined CYP4F2*3 genotype. Specifically, the investigators will test for an association between our novel biomarkers of long-term (plasma Factor II proteoforms) and short-term (urinary K-Acid catabolites) hepatic vitamin K concentration and CYP4F2*3 following a 10-day period of vitamin K supplementation in healthy volunteers.
Read the detailed description
The investigators will study the effect of vitamin K supplementation on two biomarkers of hepatic vitamin K concentration in groups with defined CYP4F2*3 genotype. Specifically, the investigators will test for an association between our novel biomarkers of long-term (plasma Factor II proteoforms) and short-term (urinary K-Acid catabolites) hepatic vitamin K concentration and CYP4F2*3 following a 10-day period of vitamin K supplementation in healthy volunteers.
The investigators will recruit, by posted advertisements at UWMC, male and female healthy volunteers. A two-step selection process will be employed. Subjects will self-select by responding to flyers, and contact the research coordinator. The research coordinator will screen them for eligibility over the phone and if eligible, make an appointment for the first study visit. For the first phase, the Research Coordinator will collect a buccal swab of DNA from ~ 200 eligible candidates; the DNA will be tested for absence or presence of the CYP4F2*3 variant allele. The PI and Research Coordinator will review the genotyping results and then select 14 individuals with either a homozygous CYP4F2*3 genotype or a heterozygous CYP4F2*1/*3 genotype, and a demographically matched group of 14 with a homozygous CYP4F2*1 genotype at the diagnostic locus for the supplementation phase of the study. The study coordinator will then contact these subjects by phone for Phase II participation.
Procedures - Phase I, Buccal Swab Collection for DNA Isolation.
Demographic Questionnaire: Self-reported heritage, age, and sex will be collected through a brief demographic questionnaire.
Buccal Swab: We will collect cheek cells with a cotton swab and isolate DNA and test for the CYP4F2*1 and CYP4F2*3 alleles.
Genotyping: CYP4F2 genotype will be determined by a validated TaqMan assay (ABI/ThermoFisher Scientific), using commercially available DNA hybridization probes to test for the absence or presence of the CYP4F2*3 allele. Subjects who are either a homozygous CYP4F2*3 genotype or a heterozygous CYP4F2*1/*3 genotype, and CYP4F2*3 alleles will be eligible for Phase II.
Procedures - Phase II, Vitamin K Supplementation.
Vitamin K Supplementation: Research participants selected for the supplementation study based on CYP4F2 genotype will be given 1-mg/day phylloquinone (Vitacost; Natures Life K-1 Phylloquinone) for 10 consecutive days. Each dose will be taken in the morning (~ 8 am), with one half pint of 2% milk to facilitate absorption.
Sample Collection: For the supplementation study, a venous blood sample (10 mL EDTA tube) and a spot urine sample will be collected after an overnight fast from d1 through d5 and on d8 and d10 of Vitamin K supplementation for 10 days. Plasma will be isolated and both samples will be stored at -70°C until analysis. Women of child-bearing potential will have a urine pregnancy test of d1 and if positive, will be withdrawn from the study, and all samples and data will be destroyed.
Measurement of Plasma Factor II Proteoforms: Plasma concentration of the 11 individual proteoforms of Factor II will be measured byLC-MS/MS. This data will be used to calculate three metrics of long-term vitamin K status, unFII, ucFII:iFII and inFII:aFII. These represent different mathematical measures of the degree of Factor II undercarboxylation. Prospective analysis of plasma vitamin K1, PIVKA II and ucOC is not planned, but will be held in reserve should the need for that data arise.
Measurement of Urinary K-Acid I and II: Quantitation of K-Acid I and II, and creatinine (Cr) in spot urine samples will be performed, using a validated LC-MS/MS assay that the investigators have recently developed. The total and individual urinary K-Acid/Cr ratio will be computed.
Statistical Analysis Plan: The investigators will conduct an unpaired t-test to compare the mean response to vitamin K supplementation in the two CYP4F2 genotype groups. Response is defined as the area under the vitamin K status value x time curve, corrected for baseline, for the 10-day intervention period. A secondary metric will be the absolute peak change in the vitamin K status ratio. Both short (urinary K-Acid/Cr ratio) and long-term (ucFII:iFII and inFII:aFII) biomarkers will tested separately. Based on pilot data, a sample size of 14 in each genotype group will provide a power of at least 80% to detect a significant effect at the significance 0.05 level, when there is a two-fold difference in the response to supplementation.
- Conditions
- Vitamin K Status
- Being tested
- Phase I, Buccal Swab Collection for DNA Isolation, Phase II, Vitamin K (Vitacost) Supplementation
- Keywords
- vitamin K, pharmacogenetics, blood clotting factors, CYP4F2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Phase I, Buccal Swab Collection for DNA IsolationGenetic
Buccal swab will be taken from study participants for DNA isolation.
Phase II, Vitamin K (Vitacost) SupplementationDietary supplement
1-mg/day phylloquinone (Vitacost; Natures Life K-1 Phylloquinone) for 10 consecutive days. Each dose will be taken in the morning (~ 8 am), with one half pint of 2% milk to facilitate absorption. Blood and urine samples collection before and during the vitamin K supplementation period.
| Study group | Role | What they receive |
|---|---|---|
| Phase I, Buccal Swab Collection for DNA Isolation | Experimental | Approximately 200 healthy volunteers recruited. They complete a brief demographic survey and a undergo one-time buccal swab for collection of cheek cells for DNA analysis. Receives: Genetic: Phase I, Buccal Swab Collection for DNA Isolation |
| Phase II, Vitamin K (Vitacost) Supplementation | Experimental | Subjects from Phase I with a homozygous CYP4F2*1 (n=14) or CYP4F2*3 carriers (n=14) are selected to receive daily vitamin K supplementation, for 10-days. Blood and urine samples are collected sequentially, at baseline, and during the supplementation period. Receives: Dietary Supplement: Phase II, Vitamin K (Vitacost) Supplementation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Short-term Hepatic Vitamin K Status-1
urinary vitamin K-acid/creatinine ratio
Measured: 10-days
Long-term Hepatic Vitamin K Status
plasma factor II carboxylation state
Measured: 10-days
Secondary outcomes (1)
Short-term Hepatic Vitamin K Status-2
Plasma vitamin K acid concentration
Measured: 10-days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2020
- Study start25 Aug 2017
- Primary completion31 Jul 2023
- Study completion31 Jul 2023
Why it stopped: Insufficient funds to complete the study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Vitamin K StatusStudies of the same condition, open and under way.
- More trials run by University of WashingtonThe 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
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- This is a two-phase study. Healthy adults are screened by genetic analysis in phase I and two sub-groups with specific CYP4F2 genotypes (\*1/\*1 and \*1/\*3 or \*3/\*3) are selected to receive vitamin K supplementation in phase II.
- Masking
- None (open label)
- Enrolment
- 106 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of General Medical Sciences (NIGMS)
- Responsible party
- Principal investigator, Kenneth Thummel, University of Washington
- Investigators
- Kenneth E Thummel, PhD, Principal investigator, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04450212
- Sponsor's protocol ID
- STUDY00001593
- Other IDs
- P01GM116691-02S1
- Status last verified
- Dec 2023
- First submitted
- 22 Jun 2020
- Last updated
- 19 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vitamin K Supplementation Study in Healthy Volunteers (Aim 2B)
- ClinicalTrials.gov ID
- NCT04450212
- Acronym / sponsor ID
- STUDY00001593
- Conditions
- Vitamin K Status
- Keywords
- vitamin K, pharmacogenetics, blood clotting factors, CYP4F2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Insufficient funds to complete the study.
- Enrolment
- 106 participants (actual)
- Lead sponsor
- University of WashingtonUniversity, hospital or other
- Collaborators
- National Institute of General Medical Sciences (NIGMS)
- Study start
- 25 Aug 2017 (actual)
- Primary completion
- 31 Jul 2023 (actual)
- Study completion
- 31 Jul 2023 (actual)
- First posted
- 29 Jun 2020 (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 overall purpose of this study is to determine how variation in the CYP4F2 gene modulates the synthesis of vitamin K-dependent clotting factors. We propose that the CYP4F2*3 gene variant increases short- and long-term vitamin K concentrations in the liver by reducing the efficiency of vitamin K metabolism. The investigators will study the effect of vitamin K supplementation on two biomarkers of hepatic vitamin K concentration in groups with defined CYP4F2*3 genotype. Specifically, the investigators will test for an association between our novel biomarkers of long-term (plasma Factor II proteoforms) and short-term (urinary K-Acid catabolites) hepatic vitamin K concentration and CYP4F2*3 following a 10-day period of vitamin K supplementation in healthy volunteers.
Detailed description
The investigators will study the effect of vitamin K supplementation on two biomarkers of hepatic vitamin K concentration in groups with defined CYP4F2*3 genotype. Specifically, the investigators will test for an association between our novel biomarkers of long-term (plasma Factor II proteoforms) and short-term (urinary K-Acid catabolites) hepatic vitamin K concentration and CYP4F2*3 following a 10-day period of vitamin K supplementation in healthy volunteers.
The investigators will recruit, by posted advertisements at UWMC, male and female healthy volunteers. A two-step selection process will be employed. Subjects will self-select by responding to flyers, and contact the research coordinator. The research coordinator will screen them for eligibility over the phone and if eligible, make an appointment for the first study visit. For the first phase, the Research Coordinator will collect a buccal swab of DNA from ~ 200 eligible candidates; the DNA will be tested for absence or presence of the CYP4F2*3 variant allele. The PI and Research Coordinator will review the genotyping results and then select 14 individuals with either a homozygous CYP4F2*3 genotype or a heterozygous CYP4F2*1/*3 genotype, and a demographically matched group of 14 with a homozygous CYP4F2*1 genotype at the diagnostic locus for the supplementation phase of the study. The study coordinator will then contact these subjects by phone for Phase II participation.
Procedures - Phase I, Buccal Swab Collection for DNA Isolation.
Demographic Questionnaire: Self-reported heritage, age, and sex will be collected through a brief demographic questionnaire.
Buccal Swab: We will collect cheek cells with a cotton swab and isolate DNA and test for the CYP4F2*1 and CYP4F2*3 alleles.
Genotyping: CYP4F2 genotype will be determined by a validated TaqMan assay (ABI/ThermoFisher Scientific), using commercially available DNA hybridization probes to test for the absence or presence of the CYP4F2*3 allele. Subjects who are either a homozygous CYP4F2*3 genotype or a heterozygous CYP4F2*1/*3 genotype, and CYP4F2*3 alleles will be eligible for Phase II.
Procedures - Phase II, Vitamin K Supplementation.
Vitamin K Supplementation: Research participants selected for the supplementation study based on CYP4F2 genotype will be given 1-mg/day phylloquinone (Vitacost; Natures Life K-1 Phylloquinone) for 10 consecutive days. Each dose will be taken in the morning (~ 8 am), with one half pint of 2% milk to facilitate absorption.
Sample Collection: For the supplementation study, a venous blood sample (10 mL EDTA tube) and a spot urine sample will be collected after an overnight fast from d1 through d5 and on d8 and d10 of Vitamin K supplementation for 10 days. Plasma will be isolated and both samples will be stored at -70°C until analysis. Women of child-bearing potential will have a urine pregnancy test of d1 and if positive, will be withdrawn from the study, and all samples and data will be destroyed.
Measurement of Plasma Factor II Proteoforms: Plasma concentration of the 11 individual proteoforms of Factor II will be measured byLC-MS/MS. This data will be used to calculate three metrics of long-term vitamin K status, unFII, ucFII:iFII and inFII:aFII. These represent different mathematical measures of the degree of Factor II undercarboxylation. Prospective analysis of plasma vitamin K1, PIVKA II and ucOC is not planned, but will be held in reserve should the need for that data arise.
Measurement of Urinary K-Acid I and II: Quantitation of K-Acid I and II, and creatinine (Cr) in spot urine samples will be performed, using a validated LC-MS/MS assay that the investigators have recently developed. The total and individual urinary K-Acid/Cr ratio will be computed.
Statistical Analysis Plan: The investigators will conduct an unpaired t-test to compare the mean response to vitamin K supplementation in the two CYP4F2 genotype groups. Response is defined as the area under the vitamin K status value x time curve, corrected for baseline, for the 10-day intervention period. A secondary metric will be the absolute peak change in the vitamin K status ratio. Both short (urinary K-Acid/Cr ratio) and long-term (ucFII:iFII and inFII:aFII) biomarkers will tested separately. Based on pilot data, a sample size of 14 in each genotype group will provide a power of at least 80% to detect a significant effect at the significance 0.05 level, when there is a two-fold difference in the response to supplementation.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This is a two-phase study. Healthy adults are screened by genetic analysis in phase I and two sub-groups with specific CYP4F2 genotypes (*1/*1 and *1/*3 or *3/*3) are selected to receive vitamin K supplementation in phase II.
| Arm | Type | Receives |
|---|---|---|
| Phase I, Buccal Swab Collection for DNA Isolation | Experimental | Genetic: Phase I, Buccal Swab Collection for DNA IsolationApproximately 200 healthy volunteers recruited. They complete a brief demographic survey and a undergo one-time buccal swab for collection of cheek cells for DNA analysis. |
| Phase II, Vitamin K (Vitacost) Supplementation | Experimental | Dietary Supplement: Phase II, Vitamin K (Vitacost) SupplementationSubjects from Phase I with a homozygous CYP4F2*1 (n=14) or CYP4F2*3 carriers (n=14) are selected to receive daily vitamin K supplementation, for 10-days. Blood and urine samples are collected sequentially, at baseline, and during the supplementation period. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Participants will be males or females 18 years and older.
- Participants must read and understand English.
- Participants must be able to provide informed consent.
- Women not currently pregnant or lactating.
Key exclusion criteria (4 listed)
- Participants less than 18 years of age.
- Participants unable to read and understand English.
- Participants unable to provide informed consent.
- Women who are pregnant or lactating.
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 |
|---|---|---|
| Phase I, Buccal Swab Collection for DNA IsolationBuccal swab will be taken from study participants for DNA isolation. | Genetic | Phase I, Buccal Swab Collection for DNA Isolation |
| Phase II, Vitamin K (Vitacost) Supplementation1-mg/day phylloquinone (Vitacost; Natures Life K-1 Phylloquinone) for 10 consecutive days. Each dose will be taken in the morning (~ 8 am), with one half pint of 2% milk to facilitate absorption. Blood and urine samples collection before and during the vitamin K supplementation period. | Dietary supplement | Phase II, Vitamin K (Vitacost) Supplementation |
Primary outcome
Short-term Hepatic Vitamin K Status-1
Time frame: 10-days
urinary vitamin K-acid/creatinine ratio
Long-term Hepatic Vitamin K Status
Time frame: 10-days
plasma factor II carboxylation state
1 secondary outcome
Short-term Hepatic Vitamin K Status-2
Time frame: 10-days
Results and safety
The study was stopped early (reason given: Insufficient funds to complete the study.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2023.
- Individual participant dataSharing planned: No
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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.
Kenneth E Thummel, PhD principal investigator
University of Washington
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Phase I, Buccal Swab Collection for DNA Isolation and Phase II, Vitamin K (Vitacost) Supplementation in people with Vitamin K Status, run by University of Washington at 1 site in United States.
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 4 inclusion and 4 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: stopped early, as of the sponsor's last update on 19 Dec 2023. 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 United States. 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. 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?
The study was stopped early (reason given: Insufficient funds to complete the 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?
Short-term Hepatic Vitamin K Status-1 (time frame: 10-days). The study lists 2 primary outcomes in all. 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 19 Dec 2023.