Pharmacogenomics of Thiazolidinediones
Condition: Type 2 Diabetes
MeSH terms: Diabetes Mellitus, Type 2
Study type: Interventional

Summary: 
      The purpose of this study is to determine predictors of response to pioglitazone, an
      anti-diabetic medication. The investigators know from randomized clinical trials that some
      30% of patients do not respond to this type of medication. There is presently no way to
      identify this group of patients leading to unnecessary drug exposure and medication costs.
    

Detailed description: 
      In phase I, subjects who are eligible based on height and weight and general health
      information will sign informed consent. In phase II, subjects will be screened to ensure that
      they fit the inclusion/exclusion criteria, including an oral glucose tolerance test. Other
      blood tests will be performed to check complete blood count, lipids, liver functions and
      electrolytes.

      Qualifying volunteers will enter phase III, which will consist of outpatient radioimaging and
      body composition, metabolic testing (intravenous glucose tolerance test), and tissue
      biopsies. Blood will also be drawn for genetic testing and for microarray studies of
      leukocytes. Written medication information and instructions for pioglitazone, discharge
      instructions and satisfaction surveys following the tissue biopsy procedures will be given to
      subjects during the study. During phase IV, subjects will begin pioglitazone therapy. Every 4
      weeks throughout the drug intervention, glycemic control, lipoprotein profile, and weight
      will be monitored. After 12 weeks of pioglitazone therapy, the X-ray and magnetic resonance
      (MR) measurements of body composition, the biopsies and the metabolic tests performed during
      phase III will be repeated (phase V), and blood will be drawn for microarray studies of
      leukocytes.

      Thereafter, subjects will have the option to be enrolled in a 10 week, behavioral weight loss
      program (phase VI). Following the 10-week weight loss program, a few outcome measurements
      will be repeated (phase VII).

      Throughout the study, Women of Child Bearing Potential (WCBP) will have human human chorionic
      gonadotrophin (HCG) urine pregnancy tests. Pregnancy tests will only be performed on Women of
      childbearing potential, meaning women who are pre-menopausal and who have not had surgical
      sterilization. Women who have not had a hysterectomy or tubal ligation at least six months
      prior to signing informed consent or have been postmenopausal for at least one year, will be
      instructed to practice one of the following methods of birth control throughout the study:
      oral, transdermal, or implantable hormonal contraceptives, intrauterine device, diaphragm
      plus spermicide, condom plus spermicide, or abstinence. Pioglitazone may reduce the
      effectiveness of some hormonal types of contraceptives. Women using hormonal methods of birth
      control will be advised to use a barrier method as well. Female subjects are informed to
      notify the investigators immediately if they think they might have become pregnant during the
      study.

      Participants who are eligible have 10 visits over an approximate 15-week period. Participants
      can choose to participate in an optional weight management program for an additional 10 weeks
      after treatment and before their final visit.
    

Intervention name(s): Pioglitazone
Intervention type(s): Drug
Intervention description(s): 30 mg tablet once daily for 4 weeks, then increased to 45 mg once daily for an additional 8 weeks. Total dosage period is 12 weeks.
Other intervention name(s): Actos
Intervention MeSH terms: Pioglitazone
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Pioglitazone; Type 2 diabetes; Insulin sensitivity; Healthy adults; Thiazolidinediones; Pharmacogenetics