Ignite Creation Date:
2024-05-05 @ 9:49 PM
Last Modification Date:
2024-10-26 @ 10:10 AM
Study NCT ID:
NCT00975169
Status:
UNKNOWN
Last Update Posted:
2010-03-18
First Post:
2009-09-10
Brief Title:
Association Study of Genetic Polymorphisms of Candidate Genes With Thiazolidinedione-Related Peripheral Edema and Drug Responsiveness
Sponsor:
National Taiwan University Hospital
Organization:
National Taiwan University Hospital
Study Overview
Official Title:
Association Study of Genetic Polymorphisms of Candidate Genes With Thiazolidinedione-Related Peripheral Edema and Drug Responsiveness
Status:
UNKNOWN
Status Verified Date:
2010-03
Last Known Status:
RECRUITING
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:
According to the above evidence though the exact mechanism contributing to the Thiazolidinediones TZDs associated peripheral edema is still unclear the investigators hypothesize that the genetic variations of certain candidate genes involved in peroxisome proliferator-activated receptor PPAR gamma itself and PPAR gamma-regulated genes may contribute to TZDs-associated peripheral edema Therefore the investigators plan to conduct a case-control study to test the association between single nucleotide polymorphisms SNPs in certain candidate genes and TZDs related peripheral edema
A large fraction of individuals both with type 2 diabetes 38-41 or who are at risk for type 2 diabetes do not respond to TZD therapy In individuals with type 2 diabetes non-response has not been carefully characterized but data from studies in at-risk individuals suggests that a lack of improvement in insulin sensitivity Si may account for the lack of response to TZD therapy In the Troglitazone In the Prevention Of Diabetes TRIPOD study around 30 of treated women did not show an improvement in Si they gained no protection from type 2 diabetes when compared with the placebo group Assessment of baseline clinical and physiologic measurements revealed similar levels of adiposity fasting glucose and insulin Si and β-cell function fasting lipids contraceptive use and compliance with study medication between responders and nonresponders suggesting that these measures do not predict TZD response
The adipose tissue-derived hormone adiponectin improves insulin sensitivity and its circulating levels are decreased in obesity induced insulin resistance In obob mice lacking adiponectin the ability of PPARγ agonists TZDs to improve glucose tolerance is diminished It implied that adiponectin is an important contributor to PPARγ-mediated improvements in glucose tolerance through mechanisms that involve the activation of the AMPK pathway On the other hand it has been shown that FOXO1 repressed PPARγ1 and γ2 promoters in primary adipocytes It has also been reported that peroxisome proliferators activated receptor-γ coactivator-1α PGC-1α gene expression in brown and white adipocytes is a direct target of TZDs and activators of retinoid X receptor RXR Taken together both FOXO1 and PGC-1α potentially played important roles on the antidiabetic action of TZDs
In summary though TZDs have been widely used in patients with type 2 diabetes mellitus some of patients experienced TZD-related peripheral edema and some of patients had no good responsiveness to TZDs The underlying contributing factors and molecular mechanisms have not been clearly elucidated In this study the investigators will identify the contributing factors of TZD-related peripheral edema and responsiveness to TZDs The investigators will also identify the association of single nucleotide polymorphisms SNPs of certain candidate genes with TZD related peripheral edema and responsiveness to TZDs It may identify some clinical and pharmacogenetic factors to predict the occurrence of TZD-related edema and the responsiveness to TZDs
A large fraction of individuals both with type 2 diabetes 38-41 or who are at risk for type 2 diabetes do not respond to TZD therapy In individuals with type 2 diabetes non-response has not been carefully characterized but data from studies in at-risk individuals suggests that a lack of improvement in insulin sensitivity Si may account for the lack of response to TZD therapy In the Troglitazone In the Prevention Of Diabetes TRIPOD study around 30 of treated women did not show an improvement in Si they gained no protection from type 2 diabetes when compared with the placebo group Assessment of baseline clinical and physiologic measurements revealed similar levels of adiposity fasting glucose and insulin Si and β-cell function fasting lipids contraceptive use and compliance with study medication between responders and nonresponders suggesting that these measures do not predict TZD response
The adipose tissue-derived hormone adiponectin improves insulin sensitivity and its circulating levels are decreased in obesity induced insulin resistance In obob mice lacking adiponectin the ability of PPARγ agonists TZDs to improve glucose tolerance is diminished It implied that adiponectin is an important contributor to PPARγ-mediated improvements in glucose tolerance through mechanisms that involve the activation of the AMPK pathway On the other hand it has been shown that FOXO1 repressed PPARγ1 and γ2 promoters in primary adipocytes It has also been reported that peroxisome proliferators activated receptor-γ coactivator-1α PGC-1α gene expression in brown and white adipocytes is a direct target of TZDs and activators of retinoid X receptor RXR Taken together both FOXO1 and PGC-1α potentially played important roles on the antidiabetic action of TZDs
In summary though TZDs have been widely used in patients with type 2 diabetes mellitus some of patients experienced TZD-related peripheral edema and some of patients had no good responsiveness to TZDs The underlying contributing factors and molecular mechanisms have not been clearly elucidated In this study the investigators will identify the contributing factors of TZD-related peripheral edema and responsiveness to TZDs The investigators will also identify the association of single nucleotide polymorphisms SNPs of certain candidate genes with TZD related peripheral edema and responsiveness to TZDs It may identify some clinical and pharmacogenetic factors to predict the occurrence of TZD-related edema and the responsiveness to TZDs
Detailed Description:
None
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