Vitamin K Supplementation Study in Healthy Volunteers (Aim 2B)
NCT ID: NCT04450212
Last Updated: 2023-12-19
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
TERMINATED
NA
106 participants
INTERVENTIONAL
2017-08-25
2023-07-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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
See the medical conditions and disease areas that this research is targeting or investigating.
Keywords
Explore important study keywords that can help with search, categorization, and topic discovery.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
PARALLEL
BASIC_SCIENCE
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Phase I, Buccal Swab Collection for DNA Isolation
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.
Phase I, Buccal Swab Collection for DNA Isolation
Buccal swab will be taken from study participants for DNA isolation.
Phase II, Vitamin K (Vitacost) Supplementation
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.
Phase II, Vitamin K (Vitacost) Supplementation
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.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Phase I, Buccal Swab Collection for DNA Isolation
Buccal swab will be taken from study participants for DNA isolation.
Phase II, Vitamin K (Vitacost) Supplementation
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.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
2. Participants must read and understand English.
3. Participants must be able to provide informed consent.
4. Women not currently pregnant or lactating.
Exclusion Criteria
2. Participants unable to read and understand English.
3. Participants unable to provide informed consent.
4. Women who are pregnant or lactating.
18 Years
ALL
Yes
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Institute of General Medical Sciences (NIGMS)
NIH
University of Washington
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Kenneth Thummel
Professor: Pharmaceutics
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Kenneth E Thummel, PhD
Role: PRINCIPAL_INVESTIGATOR
University of Washington
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
University of Washington
Seattle, Washington, United States
Countries
Review the countries where the study has at least one active or historical site.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
STUDY00001593
Identifier Type: -
Identifier Source: org_study_id