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

Insulin Sensitivity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00746174
• Other study ID #: GSK CRT49653/250
• Status: Completed
• Phase: Phase 4
• First received: August 29, 2008
• Last updated: September 2, 2008
• Start date: February 2004
• Est. completion date: February 2008

Study information

• Verified date: September 2008
• Source: University of Texas Southwestern Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: February 2008
• Est. primary completion date: March 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Insulin Resistance
• Insulin Sensitivity

Intervention

Drug:
• Rosiglitazone
Rosiglitazone 8mg PO daily for 16 weeks
• Placebo
Placebo 1 tablet PO daily for 16 weeks

Locations

Country	Name	City	State
United States	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas

Sponsors (2)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center	GlaxoSmithKline

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Insulin sensitivity		16 weeks	No
Secondary	Intracellular lipid content in myocardium, liver and skeletal muscle		16 weeks	No
Secondary	Lipid oxidation		16 weeks	No