Japan Prevention Trial of Diabetes by Pitavastatin in Patients With Impaired Glucose Tolerance (J-PREDICT)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effects of pitavastatin for preventing diabetes in a population with impaired glucose tolerance.

Detailed Description
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Diabetes mellitus and its complications are major health problems globally. People with impaired glucose tolerance (IGT) are at high risk of developing diabetes. It is therefore important to focus on preventing diabetes in individuals with IGT. HMG-CoA reductase inhibitors (statins) are widely used for hypercholesterolemia, one of the most frequent metabolic disorders. However, there is no direct evidence to whether statins are beneficial for preventing diabetes. This study is designed to compare the efficacy of life-style modification versus life-style modification with pitavastatin (a statin) administration, in individuals with IGT.

Official Title
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Japan Prevention Trial of Diabetes by Pitavastatin in Patients With Impaired Glucose Tolerance (J-PREDICT)

Conditions
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Diabetes Mellitus, Glucose Intolerance

Intervention / Treatment
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* Other: life-style intervention
* Drug: Life style interventions plus concomitant use of pitavastatin.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion Criteria for the screening test (within 6 months before screening): LDL-cholesterol 100-159 mg/dl and/or total cholesterol 180-239 mg/dl At least one of the following: Fasting plasma glucose 100-125 mg/dl, and/or casual (non-fasting) plasma glucose 120-199 mg/dl, and/or HbA1c 5.5-6.0% At least two of the following risk factors for impaired glucose tolerance: Second degree relative with diabetes BMI >= 24 kg/m2 Systolic blood pressure >=130 mmHg, and/or diastolic blood pressure >= 85 mmHg, and/or receiving treatment for hypertension Triglyceride >= 150 mg/dl, and/or HDL < 40 mg/dl Written consent for participation in the study by their own volition after being provided sufficient explanation for the participation into this clinical trial Inclusion Criteria for the entry (Confirmed by screening test): -Impaired glucose tolerance by 75g oral glucose tolerance test (fasting plasma glucose <126 mg/dl and 2-h plasma glucose 140-199 mg/dl) Exclusion Criteria: History of diabetes (except gestational diabetes) Fasting plasma glucose >= 126 mg/dl , and/or 2-h plasma glucose >= 200 mg/dl HbA1c >= 6.5% Diabetic retinopathy Receiving with hormone replacement therapy Pancreatic diseases ( e.g. pancreatitis, pancreatectomy, pancreatic cancer), Endocrine diseases ( e.g. Cushing's syndrome, acromegaly, pheochromocytoma, aldosteronism, hyperthyroidism ) Receiving statins, fibrates or anion exchange resins Cancer or suspected cancer History of gastrectomy History of myocardial infarction, angina, or heart failure (NYHA Class >= III) Severe hypertension (SBP >= 180 mmHg or DBP >= 110 mmHg) Renal disease, including serum creatinine >= 2.0 mg/dl Hepatic disease, including transaminase (ALT or AST) >= 2 times the upper limit of normal Women hoping to become pregnant during the intended study period Contraindication or relative contraindication of Livalo® Tab(pitavastatin calcium) History of hypersensitivity to any of the ingredients of the product Severe hepatic disorder or biliary atresia Receiving cyclosporine Pregnant women, women suspected of being pregnant, or lactating women Patients receiving fibrates who also have laboratory evidence of abnormal renal function Familial hypercholesterolemia Drug abuse, alcoholism Individuals who are ineligible in the opinion of the investigator

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 74 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Pitavastatin<br>Administration of Pitavastatin | Other: life-style intervention<br>* As the life-style interventions aiming to reduce the major risks of developing diabetes mellitus, instruct the following four items:(1)set diet right, (2)maintain normal weight,(3)improve physical activity,(4)normalize smoking and alcohol drinking.<br>Drug: Life style interventions plus concomitant use of pitavastatin.<br>* Once-daily dosing of pitavastatin 1 mg(1 tablet of Livalo Tab 1 mg), or 2mg(2 tablets of Livalo Tab 1mg or 1 tablet of Livalo Tab 2mg);Dosing period of pitavastatin should be 60 months.(max.84 months).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative incidence of diabetes based on 1 positive OGTT or fasting glucose levels |  | from April, 2006 to end of March, 2012 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of newly developed diabetes |  | from April, 2006 to end of March, 2012 | 
| Cumulative incidence of diabetes based on clinical diagnosis. | Cumulative incidence of diabetes based on clinical diagnosis defined as at least one of the following:(1) Typical symptoms of diabet plus 1 positive OGTT or fasting glucose levels, (2)HbA1c>=6.5% plus 1 positive OGTT or fasting glucose levels, (3)2 positive OGTT or fasting glucose levels. | from April, 2006 to end of March, 2012 | 
| Cumulative incidence of newly developed diabetes based on 1 positive OGTT or fasting glucose levels | Cumulative incidence of newly developed diabetes based on 1 positive OGTT or fasting glucose levels (from the first administration of the study drug after the randomization) | from April, 2006 to end of March, 2012 | 
| Time until development of diabetes; Improvement in glucose tolerance |  | from April, 2006 to end of March, 2012 | 
| Incidence of any cardiovascular disease (myocardial infarction, angina, congestive heart disease, coronary revascularization, cerebral hemorrhage, cerebral infarction. |  | from April, 2006 to end of March, 2012 | 
| Incidence of coronary heart disease (myocardial infarction, angina, coronary revascularization) |  | from April, 2006 to end of March, 2012 | 
| Incidence of coronary heart disease plus cerebral infarction |  | from April, 2006 to end of March, 2012 | 
| LDL-cholesterol |  | from April, 2006 to end of March, 2012 | 
| HDL-cholesterol |  | from April, 2006 to end of March, 2012 | 
| Triglyceride |  | from April, 2006 to end of March, 2012 | 
| RLP-cholesterol |  | from April, 2006 to end of March, 2012 | 
| Adiponectin |  | from April, 2006 to end of March, 2012 | 
| High sensitive CRP |  | from April, 2006 to end of March, 2012 | 
| Asymmetrical dimethyl arginine (ADMA) |  | from April, 2006 to end of March, 2012 | 
| Urinary 8-OHd |  | from April, 2006 to end of March, 2012 | 
| Fasting plasma glucose |  | from April, 2006 to end of March, 2012 | 
| 2-h plasma glucose during 75g oral glucose tolerance test |  | from April, 2006 to end of March, 2012 | 
| HbA1c |  | from April, 2006 to end of March, 2012 | 
| Insulin |  | from April, 2006 to end of March, 2012 | 
| HOMA-R |  | from April, 2006 to end of March, 2012 | 
| HOMA-β |  | from April, 2006 to end of March, 2012 | 
| Insulinogenic index |  | from April, 2006 to end of March, 2012 | 
| Time until dropout |  | from April, 2006 to end of March, 2012 | 
| Number of adverse events |  | from April, 2006 to end of March, 2012 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glucose intolerance, Diabetes mellitus, Statins,HMG-CoA