Pharmacogenomics of Thiazolidinediones (PPAR)

This study is currently recruiting participants.
Verified January 2013 by University of Maryland
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Soren Snitker, MD, University of Maryland
ClinicalTrials.gov Identifier:
NCT01135394
First received: June 1, 2010
Last updated: January 15, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention
Type 2 Diabetes
Drug: Pioglitazone

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Pharmacogenomics of Thiazolidinediones

Resource links provided by NLM:


Further study details as provided by University of Maryland:

Primary Outcome Measures:
  • Characterize the variability in response to thiazolidinediones (TZDs) at the physiological, cellular and molecular levels. [ Time Frame: 12 to 24 weeks ] [ Designated as safety issue: No ]
    The outcome will be measured for each subject at the end of their participation (12 to 24 weeks). However, analysis of these outcomes will occur at the completion of all subject participation.


Secondary Outcome Measures:
  • Define genes whose regulation correlates to TZD response. [ Time Frame: 12 to 24 weeks ] [ Designated as safety issue: No ]
    The outcome will be measured for each subject at the end of their participation (12 to 24 weeks). However, analysis of these outcomes will occur at the completion of all subject participation.

  • Identify the SNPs and haplotypes in candidate genes that influence TZD response. [ Time Frame: 12 to 24 weeks ] [ Designated as safety issue: No ]
    The outcome will be measured for each subject at the end of their participation (12 to 24 weeks). However, analysis of these outcomes will occur at the completion of all subject participation.


Estimated Enrollment: 134
Study Start Date: March 2009
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pioglitazone (Actos)
Participants will have metabolism studies to consist of outpatient X-ray and MR measurements of bone density and body composition, metabolic testing (intravenous glucose tolerance test), and muscle and adipose tissue biopsies. Blood will also be drawn for genetic testing and for microarray studies of leukocytes. Upon completion of the above studies, the participant 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 MR measurements of body composition, the biopsies, microarray studies for leukocytes and the metabolic tests will be repeated.
Drug: Pioglitazone
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 Name: Actos

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 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 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.

  Eligibility

Ages Eligible for Study:   35 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age 35-64
  • BMI: ≥ 25 and ≤ 40

Exclusion Criteria:

  • Pregnancy as determined by urine pregnancy test Breast-feeding, or planning to become pregnant during the study
  • Physical dimensions exceeding the limits of any equipment used
  • Stage III or greater congestive heart failure
  • Symptomatic peripheral vascular disease
  • Stroke
  • Severe hypertension (>170/100 mmHg)
  • Anemia (Hgb and Hct < normal reference range)
  • Receiving treatment for thyroid, pituitary, kidney or liver disease (except controlled thyroid hormone replacement)
  • History of diabetes (as told by doctor, or taking diabetic medications Fasting glucose value diagnostic for diabetes 2-h oral glucose tolerance test diagnostic for diabetes
  • Rheumatoid arthritis
  • History of wrist, hip or leg fracture after the age of 45
  • History of kidney stones
  • Medications that the investigator judges will make interpretation of the results difficult or increase the risk of participation (e.g. anticoagulants)
  • Any disease or condition that the investigator judges will affect bone metabolism or make interpretation of the results difficult or increase the risk of participation (e.g. anemia, cardiac decompensation, intolerance to pioglitazone, lidocaine, or other agents used)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01135394

Contacts
Contact: Soren Snitker, MD, PhD 410-706-1511 ssnitker@medicine.umaryland.edu
Contact: Suzanne B Treadway, MS, RN, CCRP 410-706-6284 streadway@medicine.umaryland.edu

Locations
United States, Maryland
University of Maryland School of Medicine Recruiting
Baltimore, Maryland, United States, 21201
Contact: Soren Snitker, MD, PhD    410-706-1511    ssnitker@medicine.umaryland.edu   
Contact: Suzanne B Treadway, MS, RN, CCRP    410-706-6284    streadway@medicine.umaryland.edu   
Principal Investigator: Soren Snitker, MD, PhD         
Sub-Investigator: Richard B Horenstein, MD         
Sub-Investigator: Charmaine D Rochester, PharmD         
Sub-Investigator: Charlene Hafer-Macko, MD         
Sub-Investigator: Alan R Shuldiner, MD         
Sub-Investigator: Lida Tabatabaeian, MD         
Sub-Investigator: Da-Wei Gong, MD, PhD         
Sub-Investigator: Hegang Chen, PhD         
Sub-Investigator: Carole Sztalryd-Woodle, PhD         
Sub-Investigator: Urmila Sreenivasan, PhD         
Sponsors and Collaborators
University of Maryland
Investigators
Principal Investigator: Soren Snitker, MD, PhD University of Maryland
  More Information

No publications provided

Responsible Party: Soren Snitker, MD, MD, PhD, University of Maryland
ClinicalTrials.gov Identifier: NCT01135394     History of Changes
Other Study ID Numbers: HP-00043497, R01DK074828
Study First Received: June 1, 2010
Last Updated: January 15, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Maryland:
Pioglitazone
Type 2 diabetes
Insulin sensitivity
Healthy adults
Thiazolidinediones
Pharmacogenetics

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

ClinicalTrials.gov processed this record on April 20, 2014