Ignite Creation Date:
2024-05-06 @ 2:53 PM
Last Modification Date:
2024-10-26 @ 1:38 PM
Study NCT ID:
NCT04450212
Status:
TERMINATED
Last Update Posted:
2023-12-19
First Post:
2020-06-22
Brief Title:
Vitamin K Supplementation Study in Healthy Volunteers Aim 2B
Sponsor:
University of Washington
Organization:
University of Washington
Study Overview
Official Title:
Vitamin K Supplementation Study in Healthy Volunteers Aim 2B
Status:
TERMINATED
Status Verified Date:
2023-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Insufficient funds to complete the study
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 CYP4F23 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 CYP4F23 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 CYP4F23 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 CYP4F23 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 CYP4F23 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 CYP4F23 variant allele The PI and Research Coordinator will review the genotyping results and then select 14 individuals with either a homozygous CYP4F23 genotype or a heterozygous CYP4F213 genotype and a demographically matched group of 14 with a homozygous CYP4F21 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 CYP4F21 and CYP4F23 alleles
Genotyping CYP4F2 genotype will be determined by a validated TaqMan assay ABIThermoFisher Scientific using commercially available DNA hybridization probes to test for the absence or presence of the CYP4F23 allele Subjects who are either a homozygous CYP4F23 genotype or a heterozygous CYP4F213 genotype and CYP4F23 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-mgday 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 -70C 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-MSMS This data will be used to calculate three metrics of long-term vitamin K status unFII ucFIIiFII and inFIIaFII 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-MSMS assay that the investigators have recently developed The total and individual urinary K-AcidCr 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-AcidCr ratio and long-term ucFIIiFII and inFIIaFII 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 005 level when there is a two-fold difference in the response to supplementation
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 CYP4F23 variant allele The PI and Research Coordinator will review the genotyping results and then select 14 individuals with either a homozygous CYP4F23 genotype or a heterozygous CYP4F213 genotype and a demographically matched group of 14 with a homozygous CYP4F21 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 CYP4F21 and CYP4F23 alleles
Genotyping CYP4F2 genotype will be determined by a validated TaqMan assay ABIThermoFisher Scientific using commercially available DNA hybridization probes to test for the absence or presence of the CYP4F23 allele Subjects who are either a homozygous CYP4F23 genotype or a heterozygous CYP4F213 genotype and CYP4F23 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-mgday 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 -70C 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-MSMS This data will be used to calculate three metrics of long-term vitamin K status unFII ucFIIiFII and inFIIaFII 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-MSMS assay that the investigators have recently developed The total and individual urinary K-AcidCr 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-AcidCr ratio and long-term ucFIIiFII and inFIIaFII 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 005 level when there is a two-fold difference in the response to supplementation
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| P01GM116691-02S1 | NIH | None | httpsreporternihgovquickSearchP01GM116691-02S1 |