Study protocol

Actos Now for the prevention of diabetes (ACT NOW) study

Ralph A DeFronzo¹ , MaryAnn Banerji² , George A Bray³ , Thomas A Buchanan⁴ , Stephen Clement⁵ , Robert R Henry⁶ , Abbas E Kitabchi⁷ , Sunder Mudaliar⁶ , Nicolas Musi¹ , Robert Ratner⁸ , Peter D Reaven⁹ , Dawn Schwenke⁹ , Frankie B Stentz⁷ and Devjit Tripathy¹

¹Texas Diabetes Institute and University of Texas Health Science Center, San Antonio, TX, USA

²Suny Health Science Center at Brooklyn, Brooklyn, NY, USA

³Pennington Biomedical Research Center/LSU, Baton Rouge, LA, USA

⁴University of Southern California Keck School of Medicine, Los Angeles, CA, USA

⁵Division of Endocrinology & Metabolism, Georgetown University, Washington, DC, USA

⁶VA San Diego Healthcare System and University of California at San Diego, USA

⁷University of Tennessee, Division of Endocrinology, Diabetes and Metabolism, Memphis, TN, USA

⁸Medstar Research Institute, Hyattsville, MD, USA

⁹Phoenix VA Health Care System, Phoenix, AZ and W.P. Carey School of Business, Arizona State University, Tempe, AZ, USA

author email corresponding author email

BMC Endocrine Disorders 2009, 9:17doi:10.1186/1472-6823-9-17

Published:	29 July 2009

Abstract

Background

Impaired glucose tolerance (IGT) is a prediabetic state. If IGT can be prevented from progressing to overt diabetes, hyperglycemia-related complications can be avoided. The purpose of the present study was to examine whether pioglitazone (ACTOS^®) can prevent progression of IGT to type 2 diabetes mellitus (T2DM) in a prospective randomized, double blind, placebo controlled trial.

Methods/Design

602 IGT subjects were identified with OGTT (2-hour plasma glucose = 140–199 mg/dl). In addition, IGT subjects were required to have FPG = 95–125 mg/dl and at least one other high risk characteristic. Prior to randomization all subjects had measurement of ankle-arm blood pressure, systolic/diastolic blood pressure, HbA_1C, lipid profile and a subset had frequently sampled intravenous glucose tolerance test (FSIVGTT), DEXA, and ultrasound determination of carotid intima-media thickness (IMT). Following this, subjects were randomized to receive pioglitazone (45 mg/day) or placebo, and returned every 2–3 months for FPG determination and annually for OGTT. Repeat carotid IMT measurement was performed at 18 months and study end. Recruitment took place over 24 months, and subjects were followed for an additional 24 months. At study end (48 months) or at time of diagnosis of diabetes the OGTT, FSIVGTT, DEXA, carotid IMT, and all other measurements were repeated.

Primary endpoint is conversion of IGT to T2DM based upon FPG ≥ 126 or 2-hour PG ≥ 200 mg/dl. Secondary endpoints include whether pioglitazone can: (i) improve glycemic control (ii) enhance insulin sensitivity, (iii) augment beta cell function, (iv) improve risk factors for cardiovascular disease, (v) cause regression/slow progression of carotid IMT, (vi) revert newly diagnosed diabetes to normal glucose tolerance.

Conclusion

ACT NOW is designed to determine if pioglitazone can prevent/delay progression to diabetes in high risk IGT subjects, and to define the mechanisms (improved insulin sensitivity and/or enhanced beta cell function) via which pioglitazone exerts its beneficial effect on glucose metabolism to prevent/delay onset of T2DM.

Trial Registration

clinical trials.gov identifier: NCT00220961