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

NCT00746174 | Completed Phase 4 DMC

• 1 other identifier: GSK CRT49653/250
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Insulin Sensitivity

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Insulin sensitivity

  16 weeks

Secondary Outcomes (2)

• Intracellular lipid content in myocardium, liver and skeletal muscle

  16 weeks

• Lipid oxidation

  16 weeks

Study Arms (2)

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

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

Interventions

Rosiglitazone DRUG

Rosiglitazone 8mg PO daily for 16 weeks

Also known as: Avandia

Rosiglitazone

Placebo DRUG

Placebo 1 tablet PO daily for 16 weeks

Placebo

Eligibility Criteria

• Age: 30 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Insulin Resistance

Interventions

Rosiglitazone

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Lidia S Szczepaniak, PhD

  University of Texas, Southwestern Medical Center at Dallas

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 29, 2008
• First Posted: September 3, 2008
• Study Start: February 1, 2004
• Primary Completion: March 1, 2007
• Study Completion: February 1, 2008
• Last Updated: September 3, 2008

Record last verified: 2008-09

Locations

US (1)