Pharmacogenomics of Thiazolidinediones

NCT ID: NCT01135394

Last Updated: 2024-03-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 114 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-03-31
• Study Completion Date: 2018-05-31

Brief 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.

Conditions

Type 2 Diabetes

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Pioglitazone

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Actos

Eligibility 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)

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

University of Maryland, Baltimore

OTHER

Sponsor Role: lead

Responsible Party

Soren Snitker

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Soren Snitker, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Maryland, Baltimore

Locations

University of Maryland School of Medicine

Baltimore, Maryland, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

R01DK074828

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HP-00043497

Identifier Type: -

Identifier Source: org_study_id