Nippon Ultra-Rapid Insulin and Diabetic Complication Evaluation-Study (NICE-Study)

Study Overview
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Brief Summary
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For the purpose of comparing efficacy of intensive therapy between 1) ultrarapid-acting type insulin (insulin aspart) and 2) conventional rapid-acting type insulin (R), a Multicenter Open Label Randomized Controlled Trial was planned in Japan using the occurrence of cardiovascular events in patients with diabetes, a high risk factor, as an index.

Detailed Description
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A survey shows that the most frequently observed direct cause of death in diabetic patients is cardiovascular disorder. However, investigations and surveys such as DCCT, UKPDS and KUMAMOTO-study, etc. clarified that strict control of blood sugar level prevented development and progress of diabetic microangiopathy, but could not show a significant effect on great vessel disorder. Recently, the DECODA-study, DECODE-study and Honolulu-study have demonstrated that postprandial high blood sugar is involved in great vessel disorder. Therefore, possible prevention of great vessel disorder in diabetic patients is suggested by improving the postprandial blood sugar level as achieved using ultrarapid-acting type insulin, which has become available recently. Even with results in Europe and the US obtained, the life-style and incidence of complications in Japanese people are different, and there are many points that remain uncertain with respect to the direct application of foreign results to Japanese people. Therefore, in Japan also, it is necessary to conduct a large-scale clinical study and to establish high-level evidence using mainly Japanese people through hospitals having many patients.

Official Title
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To Investigate Whether the Postprandial Blood Sugar Level as Achieved Using Ultrarapid-Acting Type Insulin Could Prevent Great Vessel Disorder in Japanese Type 2 Diabetic Patients.

Conditions
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Diabetes Mellitus

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects are patients satisfying the following conditions 1) - 3). Outpatients and inpatients aged 20 years or more but younger than 85 years. Men or women. Patients with type 2 diabetes based on the diagnostic standard of the Japanese Diabetes Society No specific restriction on the current treatment. Patients having switched treatment are also accepted. Exclusion Criteria: Patients with type 1 diabetes Patients with a past history of cerebral angiopathy (cerebral hemorrhage, cerebral infarction, transient cerebral ischemic attack, subarachnoid hemorrhage, etc.) within 6 months before giving consent Patients with a past history of myocardial infarction within 6 months before giving consent Patients planning to receive PTCA or CABG, or who had PTCA or CABG within 6 months before giving consent Patients with coronary arteriopathy (angina pectoris, etc.) that requires treatment with β-blocker or calcium-antagonist Patients with atrial fibrillation or atrial flutter Patients with renal dysfunction (serum creatinine ≥ 3.0 mg/dL) Patients with liver dysfunction (AST, ALT ≥ 100 IU/L) Patients with a past history or suspected of having a malignant tumor within 5 years before giving consent Pregnant or possibly pregnant patients Other patients judged inappropriate for the study by the investigators (patients presenting difficulty in frequently receiving rapid-acting type insulin or ultrarapid-acting type insulin therapy, including patients' compliance with treatment)

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 85 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| U<br>Intensified insulin therapy with ultrarapid insulin-analogue (Insulin-Aspart) | |
| R<br>Intensified insulin therapy with human regular insulin | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiovascular events 1)Sudden death 2)New development or recurrence of apoplexy or TIA 3)New development or recurrence of AMI or and angina pectoris 4)Newly developed ASO, amputation of leg due to ASO |  | five years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1)Total mortality 2)Changes in the mean IMT of common carotid arteries 3)Changes in the pulse wave velocity (PWV) (rt & 1t baPWV), ABI |  | five years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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type2 diabetes mellitus, cardiovascular disease, macrovascular event