Actos Now for Prevention of Diabetes (ACT NOW)

Study Overview
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Brief Summary
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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
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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.

Official Title
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Actos Now for Prevention of Diabetes (ACT NOW)

Conditions
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Impaired Glucose Tolerance, Type 2 Diabetes

Intervention / Treatment
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* Drug: Pioglitazone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo tablet similar to pioglitazone tablet | Drug: Placebo<br>* Placebo tablets similar to pioglitazone tablets - 1 tablet/day<br>|
| Active Comparator: Pioglitazone<br>Pioglitazone tablet similar to placebo tablet | Drug: Pioglitazone<br>* Pioglitazone tablets - 45 mg/day<br>* Other names: Actos;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevention of Type 2 Diabetes | Percentage of Participants with Type 2 Diabetes at 2.4 years Post-randomization | 2.4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Fasting Plasma Glucose of 2.4 Years | Fasting Plasma Glucose | Baseline versus 2.4 years | 
| Change From Baseline in Plasma Insulin Concentration During Oral Glucose Tolerance Test | Insulin secretion | 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. | Baseline versus 2.4 years | 
| Change in Atherosclerosis | carotid intima thickness | Baseline versus 2.4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Impaired Glucose Tolerance, Type 2 Diabetes, Prevention, Pioglitazone