Actos Now for Prevention of Diabetes (ACT NOW)

Phase 3CompletedNCT00220961

The University of Texas Health Science Center at San Antonio602 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

TRIPLE

Enrollment

602

Conditions

Impaired Glucose Tolerance Type 2 Diabetes

Interventions

PioglitazoneDRUG

Pioglitazone tablets - 45 mg/day

PlaceboDRUG

Placebo tablets similar to pioglitazone tablets - 1 tablet/day

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (8)

Carl T. Hayden VA Medical Center

Phoenix, Arizona, 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

Georgetown University

Outcomes

Primary Outcomes

Prevention of Type 2 Diabetes

Percentage of Participants with Type 2 Diabetes at 2.4 years Post-randomization

Time frame: 2.4 years

Secondary Outcomes

Change From Baseline in Fasting Plasma Glucose of 2.4 Years

Fasting Plasma Glucose

Time frame: Baseline versus 2.4 years

Change From Baseline in Plasma Insulin Concentration During Oral Glucose Tolerance Test

Insulin secretion

Time frame: Baseline versus 2.4 years

Change From Baseline in Matsuda Index of Insulin Sensitivity (There Are no Minimum/Maximum Values)

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.

Time frame: Baseline versus 2.4 years

Change in Atherosclerosis

carotid intima thickness

Time frame: Baseline versus 2.4 years

Data from ClinicalTrials.gov

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