Los Angeles,
California
90033
Purpose:
The purpose of this study is to determine if troglitazone reduces the progression of early
preintrusive carotid atherosclerosis in insulin-requiring diabetes patients.
Study summary:
Insulin resistance and hyperinsulinism appear to be important risk factors for the
development of atherosclerosis in diabetes patients. The atherogenic potential of insulin
has been shown to improve cholesterol and may have an effect on the thickness and structure
of the arterial wall. Troglitazone is an oral diabetic agent that treats insulin resistance.
Based on the initial data available, it would appear that troglitazone may be effective in
both glycemic control and improved atherosclerosis risk in diabetes patients. This study
will compare the effects of troglitazone to placebo in insulin-requiring diabetes patients
on both glycemic control and progression of atherosclerosis.
A total of 288 men and women 30 to 70 years of age with insulin-treated diabetes were
recruited and entered an 8 week run-in phase to stabilize diet, exercise, insulin dose and
glucose levels. Upon successful completion of the run-in phase, all patients were randomized
into one of two groups to receive either troglitazone 400mg/day or a matching placebo while
continuing with diet and exercise regimens and insulin dose to maintain pre-meal glucose
levels between 100 to 150 mg/dL.
Follow up visits occurred every 2 weeks for 2 months, every 4 weeks for 2 months, then every
8 weeks for the remainder of the 2-year trial. The progression of atherosclerosis was
measured by ultrasonography at baseline and every 6 months throughout the 2 years of
randomized treatment.
Criteria:
Inclusion Criteria:
- Men and women ages 30-70 years
- Diabetes: fasting glucose over 140 mg/dL but under 350 mg/dL on at least 2 occasions
- At least 30 years of age at onset of diabetes
- Metabolic control and management requiring insulin without other anti-diabetic
medications
- Willingness to sign informed consent
Exclusion Criteria:
- Known sensitivity to troglitazone or other thiazolidinediones
- For premenopausal females: pregnancy, breastfeeding, unwilling to use effective
contraception for the duration of the trial
- Active liver disease or hepatic dysfunction; renal dysfunction; high blood pressure;
major vascular events within 6 months prior to randomization; untreated
hypothyroidism or uncured hyperthyroidism; other severe or unstable disease within 5
years of randomization
- Medical illness that may require oral or parenteral glucocorticoid therapy
- Physical disability that would interfere with diabetes self-management
- Untreated or unstable diabetic retinopathy
- History of insulin allergy
- Present or recent history of alcohol intake over 5 drinks per day or substance abuse
- Participation in another clinical trial
- Currently taking nicotinic acid
Primary Contact:
Principal Investigator
Howard N. Hodis, MD
University of Southern California, Atherosclerosis Research Unit, Division of Cardiovascular Medicin