Association Study of Genetic Polymorphisms of Candidate Genes With Thiazolidinedione-Related Peripheral Edema and Drug Responsiveness

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2010 by National Taiwan University Hospital.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT00975169
First received: September 10, 2009
Last updated: March 16, 2010
Last verified: March 2010
  Purpose

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 ob/ob 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.


Condition
Diabetes Mellitus

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Retrospective
Official Title: Association Study of Genetic Polymorphisms of Candidate Genes With Thiazolidinedione-Related Peripheral Edema and Drug Responsiveness

Resource links provided by NLM:


Further study details as provided by National Taiwan University Hospital:

Primary Outcome Measures:
  • we 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 [ Time Frame: 34 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 400
Study Start Date: February 2009
Estimated Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

TZDs User, no insulin; CHF, according to New York heart Association III-V, liver cirrhosis or renal insufficiency (Cr ≥ 1.7 mg/dL) before initiation of treatment with TZDs will be excluded.

Criteria

Inclusion Criteria:

  • Clinical diagnosis of DM and with use TZDs

Exclusion Criteria:

  • Patients with the diagnosis of congestive heart failure
  • Liver cirrhosis (according to abdominal echo)
  • Renal insufficiency (Cr ≥ 1.7 mg/dL)
  • Patient with concomitant use of insulin, and/or diuretics before TZDs were excluded
  • Pregnant
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00975169

Contacts
Contact: Linda Huang 886 9 37670020 linda590203@gmail.com

Locations
Taiwan
Department of Internal Medicine, National Taiwan University Hospital Recruiting
Taipei, Taiwan
Contact: Linda Huang    886 9 67670020    linda590203@gmail.com   
Principal Investigator: Tien-Jyun Chang, Ph D         
Sponsors and Collaborators
National Taiwan University Hospital
Investigators
Principal Investigator: Tien-Jyun Chang, Ph D National Taiwan University Hospital
  More Information

No publications provided

Responsible Party: Tien-Jyun Chang, National Taiwan Univerisity Hospital
ClinicalTrials.gov Identifier: NCT00975169     History of Changes
Other Study ID Numbers: 200902005R
Study First Received: September 10, 2009
Last Updated: March 16, 2010
Health Authority: Taiwan: Department of Health

Additional relevant MeSH terms:
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
2,4-thiazolidinedione
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014