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

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

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus; Glucose Intolerance
• Intervention / Treatment: Other: life-style intervention; Drug: Life style interventions plus concomitant use of pitavastatin.

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 1240
• Phase: Phase 4

Contacts and Locations

Study Locations

• Japan
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8655
      • The University of Tokyo, Graduate School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

  1. 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%

  2. At least two of the following risk factors for impaired glucose tolerance:

     1. Second degree relative with diabetes
     2. BMI >= 24 kg/m2
     3. Systolic blood pressure >=130 mmHg, and/or diastolic blood pressure >= 85 mmHg, and/or receiving treatment for hypertension
     4. 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)

  1. History of hypersensitivity to any of the ingredients of the product
  2. Severe hepatic disorder or biliary atresia
  3. Receiving cyclosporine
  4. Pregnant women, women suspected of being pregnant, or lactating women
  5. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Pitavastatin; Administration of Pitavastatin

Other: life-style intervention; 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.; Drug: Life style interventions plus concomitant use of pitavastatin.; 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Tokyo University
• Investigators: Study Chair: Takashi Kadowaki, MD,PhD, Professor, Department of Metabolic Diseases, Graduate School of Medicine, the University of Tokyo.

Study record dates

Study Major Dates

• Study Start: April 1, 2006
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: March 5, 2006
• First Submitted That Met QC Criteria: March 9, 2006
• First Posted (Estimate): March 10, 2006

Study Record Updates

• Last Update Posted (Estimate): September 6, 2013
• Last Update Submitted That Met QC Criteria: September 5, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: Glucose intolerance; Diabetes mellitus; Statins,HMG-CoA
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Hyperglycemia; Diabetes Mellitus; Glucose Intolerance; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pitavastatin
• Other Study ID Numbers: J-PREDICT