Insulin Resistance and Intramyocellular Lipid Content in Glucose Intolerant Subjects Receiving Rosiglitazone - Full Text View

Sponsors and Collaborators:	University of Texas Southwestern Medical Center GlaxoSmithKline
Information provided by:	University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:	NCT00746174

Purpose

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.

Condition	Intervention	Phase
Insulin Sensitivity	Drug: Rosiglitazone Drug: Placebo	Phase IV

Drug Information available for: Insulin Rosiglitazone Rosiglitazone Maleate Dextrose Lipids

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Crossover Assignment
Official Title:	Insulin Resistance and Intramyocellular Lipid Content in Glucose Intolerant Subjects Receiving Rosiglitazone

Further study details as provided by University of Texas Southwestern Medical Center:

Primary Outcome Measures:

Insulin sensitivity [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Intracellular lipid content in myocardium, liver and skeletal muscle [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
Lipid oxidation [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

Enrollment:	24
Study Start Date:	February 2004
Study Completion Date:	February 2008
Primary Completion Date:	March 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Rosiglitazone: Active Comparator 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.	Drug: Rosiglitazone Rosiglitazone 8mg PO daily for 16 weeks
Placebo: Placebo Comparator 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.	Drug: Placebo Placebo 1 tablet PO daily for 16 weeks

Arms

Assigned Interventions

Rosiglitazone: Active Comparator

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.

Drug: Rosiglitazone

Rosiglitazone 8mg PO daily for 16 weeks

Placebo: Placebo Comparator

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.

Drug: Placebo

Placebo 1 tablet PO daily for 16 weeks

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.

Eligibility

Ages Eligible for Study:	30 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00746174

Locations

United States, Texas
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, United States, 75390

Sponsors and Collaborators

University of Texas Southwestern Medical Center

GlaxoSmithKline

Investigators

Principal Investigator:

Lidia S Szczepaniak, PhD

University of Texas Southwestern Medical Center at Dallas

More Information

Responsible Party:	University of Texas Southwestern Medical Center ( Lidia S. Szczepaniak, PhD. )
Study ID Numbers:	GSK CRT49653/250
Study First Received:	August 29, 2008
Last Updated:	September 2, 2008
ClinicalTrials.gov Identifier:	NCT00746174
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Texas Southwestern Medical Center:

insulin sensitivity
magnetic resonance spectroscopy (MRS)
lipotoxicity
lipid oxidation

thiazolidinediones
intracellular
triglyceride
content

Study placed in the following topic categories:

Hyperinsulinism
Metabolic Diseases
2,4-thiazolidinedione
Insulin Resistance

Metabolic disorder
Glucose Metabolism Disorders
Rosiglitazone
Insulin

Additional relevant MeSH terms:

Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 14, 2009