Ignite Creation Date:
2024-05-05 @ 11:56 AM
Last Modification Date:
2024-10-26 @ 9:17 AM
Study NCT ID:
NCT00187720
Status:
COMPLETED
Last Update Posted:
2013-01-10
First Post:
2005-09-13
Brief Title:
Genetic Basis for Variation in the Renal Elimination of Metformin
Sponsor:
University of California San Francisco
Organization:
University of California San Francisco
Study Overview
Official Title:
Genetic Basis for Variation in the Renal Elimination of Metformin
Status:
COMPLETED
Status Verified Date:
2012-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The current study is part of a large multi-investigator grant to look at the pharmacogenetics of a number of membrane transporters We will study individuals with particular genotypes of the human organic cation transporter hOCT2 to test the hypothesis that genetic variation in hOCT2 is associated with variation in the renal clearance of the antidiabetic agent metformin
Detailed Description:
The drug which is used in the treatment of Type II diabetes has a narrow therapeutic range Its net renal clearance by secretion ie renal clearance minus filtration clearance ranges from approximately 100 mlmin to 800mlmin in normal healthy subjects Although many factors may contribute to inter-individual variation in renal secretory clearance initial estimates of heritability greater than 06 suggest that genetic factors play an important role in the renal secretion of metformin Available evidence supports the idea that hOCT2 is the primary transporter involved in the first-step of renal secretion of metformin ie uptake from the blood to the tubule cell across the basolateral membrane In particular a hOCT2 is the primary organic cation transporter on the basolateral membrane of the human kidney and b metformin interacts with and is translocated by hOCT2 in heterologous expression systems
In recent studies we identified four variants M165I A270S R400C and K432Q with ethnic-specific allele frequencies 1 6 that have altered function in studies in heterologous expression systems In addition we identified a common haplotype of hOCT2 and one haplotype that contain the non-synonymous cSNP A270S We will determine whether variability in the renal secretory clearance of the model organic cation metformin in healthy individuals is associated with genetic variation in hOCT2 In particular we will determine whether the renal clearance of metformin differs in individuals who are homozygous for the common haplotype of OCT2 OCT21 and those who are heterozygous for the less common haplotype OCT23D which we have identified in a comprehensive screen of ethnically identified DNA samples We will also determine whether individuals who are heterozygous for the less common OCT2 variants M165I R400C and K432Q have reduced renal clearances of metformin
In recent studies we identified four variants M165I A270S R400C and K432Q with ethnic-specific allele frequencies 1 6 that have altered function in studies in heterologous expression systems In addition we identified a common haplotype of hOCT2 and one haplotype that contain the non-synonymous cSNP A270S We will determine whether variability in the renal secretory clearance of the model organic cation metformin in healthy individuals is associated with genetic variation in hOCT2 In particular we will determine whether the renal clearance of metformin differs in individuals who are homozygous for the common haplotype of OCT2 OCT21 and those who are heterozygous for the less common haplotype OCT23D which we have identified in a comprehensive screen of ethnically identified DNA samples We will also determine whether individuals who are heterozygous for the less common OCT2 variants M165I R400C and K432Q have reduced renal clearances of metformin
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None