Actos Now for Prevention of Diabetes (ACT NOW)

Phase 3

Completed

Brief Summary: The purpose of this study is to examine whether pioglitazone versus placebo can reduce the conversion rate of impaired glucose tolerance (IGT) to type 2 diabetes mellitus

Detailed Description: IGT is a prediabetic state. If IGT can be prevented from progressing to overt diabetes, the hyperglycemia-related complications of this devastating disease can be prevented. Subjects with IGT will be identified with an oral glucose tolerance test (OGTT). Eligible subjects also will have a measurement of first phase insulin secretion and insulin sensitivity using the frequently sampled intravenous glucose tolerance test (FSIVGTT) and carotid intimal media thickness using carotid ultrasound. Following these measurements subjects will be randomized to receive pioglitazone or placebo and they will return every 3 months for determination of fasting plasma glucose (FPG) concentration and interim medical history. Recruitment will take place over 15 months. From the time that the recruitment period ends, subjects will be followed for a total of 24 months on pioglitazone or placebo. The OGTT will be repeated at 15,27, and 39 months, or if the FPG is ≥ 126 mg/dl on the 3-month follow up visits. If the diagnosis of diabetes is established before month 39 or at month 39, the FSIVGTT and carotid ultrasound will be repeated. At 39 months, subjects will be washed out of pioglitazone or placebo and the OGTT, FSIVGTT, and carotid ultrasound will be repeated at month 45.

Recruitment & Eligibility

Inclusion Criteria

Men and women
All ethnic groups
18 years of age and older
Impaired glucose tolerance by glucose tolerance test (fasting glucose 95-125 mg/dl and 2 hr glucose of 140-199 mg/dl)
At least one of the following:
- One or more components of the insulin resistance syndrome (HDL < 40 mg/dl in females and <35 mg/dl in males, fasting triglycerides > 150 mg/dl, blood pressure > 135/85 mmHg, BMI > 24 kg/m2, waist circumference > 102 cm in men and > 88 cm in women)
- One or more first degree relatives with type 2 diabetes
- History of gestational diabetes
- Polycystic ovarian disease
- Minority ethnic background (Mexican American, African American, Asian and Pacific Islanders, Native American)

Exclusion Criteria

Type 2 diabetes
Previously treated with thiazolidinediones (ever) or metformin (within one year)
Previously treated with a sulfonylurea, a meglitinide, an alpha glucosidase inhibitor for more than a week within last year or within the 3 months prior to randomization
Previously treated with insulin (other than during pregnancy) for more than one week within the last year or within the 3 months prior to randomization
Cardiovascular disease
Hospitalization for treatment of heart disease or stroke in past 6 months
New York Heart Association Functional Class > 2
Left bundle branch block or third degree AV block
Aortic stenosis
SBP > 180 mmHg or DBP > 105 mmHg
Renal disease
Anemia
Hepatitis
GI diseases (pancreatitis, inflammatory bowel disease)
Recent or significant abdominal surgery
Advanced pulmonary disease
Chronic infections
Weight loss > 10% in past 6 months
Pregnancy and childbearing
Major psychiatric disorders
Excessive alcohol intake
Thiazide use > 25 mg per day
Non-selective beta blockers
Niacin
Systemic glucocorticoids
Weight loss or weight gain medication
Thyroid disease-suboptimally treated
Active endocrine diseases (Cushing's, acromegaly)
Plasma triglycerides over 400 mg/dl (despite treatment)
History bladder cancer
Hematuria

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo tablet similar to pioglitazone tablet
Pioglitazone	Pioglitazone	Pioglitazone tablet similar to placebo tablet

Primary Outcome Measures

Name	Time	Method
Prevention of Type 2 Diabetes	2.4 years	Percentage of Participants with Type 2 Diabetes at 2.4 years Post-randomization

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Fasting Plasma Glucose of 2.4 Years	Baseline versus 2.4 years	Fasting Plasma Glucose
Change From Baseline in Plasma Insulin Concentration During Oral Glucose Tolerance Test	Baseline versus 2.4 years	Insulin secretion
Change From Baseline in Matsuda Index of Insulin Sensitivity (There Are no Minimum/Maximum Values)	Baseline versus 2.4 years	Insulin sensitivity The Matsuda index was calculated as 10,000/square root of (pre-meal glucose x pre-meal insulin x mean 120 min post-meal glucose x mean 120 min post-meal insulin), with higher numbers indicating better the insulin sensitivity.
Change in Atherosclerosis	Baseline versus 2.4 years	carotid intima thickness

Locations (8): SUNY Health Science Center
🇺🇸
Brooklyn, New York, United States
Carl T. Hayden VA Medical Center
🇺🇸
Phoenix, Arizona, United States
University of Tennessee
🇺🇸
Memphis, Tennessee, United States
USC-Keck School of Medicine
🇺🇸
Los Angeles, California, United States
University of California San Diego-San Diego VA Medical Center
🇺🇸
San Diego, California, United States
Texas Diabetes Institute
🇺🇸
San Antonio, Texas, United States
Georgetown University
🇺🇸
Washington, District of Columbia, United States
Pennington Biomedical Research Center
🇺🇸
Baton Rouge, Louisiana, United States