Insulin Resistance and Intramyocellular Lipid Content in Glucose Intolerant Subjects Receiving Rosiglitazone

NCT ID: NCT00746174

Last Updated: 2008-09-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-02-29
• Study Completion Date: 2008-02-29

Brief Summary

This study will include subjects with an abnormal glucose tolerance test. Using a crossover design, we will evaluate the insulin sensitivity and intracellular lipid content of the heart, liver and skeletal muscle of subjects before and after therapy with Rosiglitazone and placebo. We hypothesize that Rosiglitazone will improve insulin sensitivity in association with reduced muscle lipid content that may arise either from increased lipid oxidation or enhanced storage of fat in adipose tissue.

Detailed Description

This protocol is a crossover study that will include subjects with an abnormal glucose tolerance test. Participants will be treated in a community-based practice setting and will receive detailed instruction on diet and glucose self-monitoring. The patients will be randomly assigned to treatment with 4 mg daily of Rosiglitazone or placebo. They will return to the clinic after 4 weeks to monitor changes in glucose levels, HbA1c and liver enzymes. The drug dose will be increased as indicated to 8 mg daily and the patients will be reevaluated every 4 weeks. The participants will all be admitted to the General Clinical Research Center at UT-Southwestern Medical Center at the end of 16 weeks to measure changes in the following primary endpoints: 1) insulin sensitivity, 2) lipid content of heart, liver, and skeletal muscle, 3) lipid oxidation. Additional noninvasive HMRS measurements will be made to quantify the muscle lipid content and respiratory gas exchange will be used to assess lipid oxidation. Following the GCRC admission, patients will switch to the alternative therapy for 16 additional weeks before the studies are repeated. We expect Rosiglitazone to improve insulin sensitivity in association with reduced muscle lipid content that may arise either from increased lipid oxidation or enhanced storage of fat in adipose tissue.

Conditions

Insulin Sensitivity

Keywords

insulin sensitivity; magnetic resonance spectroscopy (MRS); lipotoxicity; lipid oxidation; thiazolidinediones; intracellular; triglyceride; content

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Rosiglitazone

Subjects in this arm will be randomly assigned to treatment with Rosiglitazone 4mg daily. After 4 weeks, we will assess changes in glucose levels and liver enzymes. The dose will then be increased to Rosiglitazone 8mg daily (if indicated). The patients will be reevaluated every 4 weeks, and at the end of 16 weeks, the participants will all be admitted to the research center at UTSW to measure changes in the following: 1) insulin sensitivity; 2) lipid content of heart, liver, \& skeletal muscle; and 3) lipid oxidation using respiratory gas exchange. The patients will then switch to the alternative therapy for 16 additional weeks before the studies are repeated.

Group Type: ACTIVE_COMPARATOR

Rosiglitazone

Intervention Type: DRUG

Rosiglitazone 8mg PO daily for 16 weeks

Placebo

Subjects in this arm will be randomly assigned to treatment with placebo. After 4 weeks, we will assess changes in glucose levels and liver enzymes. The patients will be reevaluated every 4 weeks, and at the end of 16 weeks, the participants will all be admitted to the research center at UTSW to measure changes in the following: 1) insulin sensitivity; 2) lipid content of heart, liver, \& skeletal muscle; and 3) lipid oxidation using respiratory gas exchange. The patients will then switch to the alternative therapy for 16 additional weeks before the studies are repeated.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo 1 tablet PO daily for 16 weeks

Interventions

Rosiglitazone

Rosiglitazone 8mg PO daily for 16 weeks

Intervention Type: DRUG

Placebo

Placebo 1 tablet PO daily for 16 weeks

Intervention Type: DRUG

Other Intervention Names

Avandia

Eligibility Criteria

Inclusion Criteria

• Age 30-65
• Fasting plasma glucose < 126 mg/dL or plasma glucose > 140 mg/dL and <200 mg/dL two hours after a challenge with 75 gm of glucose

Exclusion Criteria

• Taking drugs known or suspected to affect intermediary metabolism (e.g. thyroid supplements, oral glucocorticoids, anabolic steroids or androgens, antidepressants, anorexic drugs, xanthine derivatives, sympathomimetics, beta-agonists)
• Taking any other investigational drugs within 30 days of starting the study
• Alcohol consumption more than 7 drinks per week
• Recreational drugs or IV drug abuse
• Acute or chronic liver diseases (SGOT >42 U/L, SGPT >48 U/L, GGT >45 U/L)
• Chronic renal insufficiency (serum creatinine >1.5 mg/dL)
• Uncontrolled hypertension (systolic/diastolic blood pressure >160/95mmHg)
• Anemia (hematocrit <35%)
• Congestive heart failure
• Metallic prostheses precluding the use of magnetic resonance imaging
• Premenopausal women without definitive measures to prevent pregnancy

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

University of Texas Southwestern Medical Center

OTHER

Sponsor Role: lead

Responsible Party

University of Texas Southwestern Medical Center

Principal Investigators

Lidia S Szczepaniak, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Texas, Southwestern Medical Center at Dallas

Locations

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, United States

Countries

United States

Other Identifiers

GSK CRT49653/250

Identifier Type: -

Identifier Source: org_study_id