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

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.

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 346

Contacts and Locations

Study Locations

• Japan
  • Osaka, Japan, 503-0012
    • Osaka Saiseikai Nakatsu Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Japanese 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/American Diabetes Association. No specific restriction on the current treatment. Patients having switched treatment are also accepted.

Description

Inclusion Criteria:

• Subjects are patients satisfying the following conditions 1) - 3).

  1. Outpatients and inpatients aged 20 years or more but younger than 85 years. Men or women.
  2. Patients with type 2 diabetes based on the diagnostic standard of the Japanese Diabetes Society
  3. No specific restriction on the current treatment. Patients having switched treatment are also accepted.

Exclusion Criteria:

1. Patients with type 1 diabetes
2. 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
3. Patients with a past history of myocardial infarction within 6 months before giving consent
4. Patients planning to receive PTCA or CABG, or who had PTCA or CABG within 6 months before giving consent
5. Patients with coronary arteriopathy (angina pectoris, etc.) that requires treatment with β-blocker or calcium-antagonist
6. Patients with atrial fibrillation or atrial flutter
7. Patients with renal dysfunction (serum creatinine ≥ 3.0 mg/dL)
8. Patients with liver dysfunction (AST, ALT ≥ 100 IU/L)
9. Patients with a past history or suspected of having a malignant tumor within 5 years before giving consent
10. Pregnant or possibly pregnant patients
11. 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)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
U; Intensified insulin therapy with ultrarapid insulin-analogue (Insulin-Aspart)
R; Intensified insulin therapy with human regular insulin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Osaka Saiseikai Nakatsu Hospital
• Investigators: Study Chair: Hideshi Kuzuya, M.D.,Ph.D, Higasiyama Takeda Hospital; Study Director: Makoto Otoshi, MD.,Ph.D., Ohtoshi Clinic; Principal Investigator: Haruo Nishimura, MD.,Ph.D., Osaka Saiseikai Nakatsu Hospital; Principal Investigator: Koji Maeda, MD., Maeda Clinic; Principal Investigator: Mitsuyo Shintani, MD.,Ph.D., Osaka Saiseikai Nakatsu Hospital

Publications and helpful links

General Publications

• Nishimura H, Shintani M, Kouji M and Nice-study group J Saiseikai Nakatsu Hospital, 20, 216-220, 2003

Study record dates

Study Major Dates

• Study Start: March 1, 2003
• Study Completion (Actual): December 1, 2007

Study Registration Dates

• First Submitted: December 17, 2007
• First Submitted That Met QC Criteria: December 17, 2007
• First Posted (Estimate): December 18, 2007

Study Record Updates

• Last Update Posted (Estimate): January 14, 2008
• Last Update Submitted That Met QC Criteria: January 7, 2008
• Last Verified: December 1, 2007

More Information

Terms related to this study

• Keywords: cardiovascular disease; type2 diabetes mellitus; macrovascular event
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus
• Other Study ID Numbers: UMIN0949; UMIN00000949