Clinical trial NCT00746174: Insulin Resistance and Intramyocellular Lipid Content in Glucose Intolerant Subjects Receiving Rosiglitazone
Official title: Insulin Resistance and Intramyocellular Lipid Content in Glucose Intolerant Subjects Receiving Rosiglitazone
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Insulin Sensitivity
Keywords: insulin sensitivity
magnetic resonance spectroscopy (MRS)
lipotoxicity
lipid oxidation
thiazolidinediones
intracellular
triglyceride
content
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2008-09-03
Enrollment: 24
Sex: ALL
Minimum age (years): 30
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Insulin sensitivity
timeFrame: 16 weeks
Secondary outcomes:
measure: Intracellular lipid content in myocardium, liver and skeletal muscle
timeFrame: 16 weeks
measure: Lipid oxidation
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center at Dallas
state: Texas
Study officials:
affiliation: University of Texas, Southwestern Medical Center at Dallas
name: Lidia S Szczepaniak, PhD
role: PRINCIPAL_INVESTIGATOR
References: