Effect of Insulin Glulisine vs Regular Human Insulin on Postprandial Endothelial Function in Type 2 Diabetes

NCT ID: NCT00562133

Last Updated: 2007-11-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-12-31
• Study Completion Date: 2007-03-31

Brief Summary

The primary objective of the study is to evaluate the postprandial time course of nitrotyrosine after injection of insulin glulisine compared with regular human insulin.

The secondary objectives are to evaluate the postprandial time course of the following efficacy parameters after injection of insulin glulisine compared with regular insulin on

• Blood Glucose
• Insulin
• Intact proinsulin
• Asymmetric dimethylarginine (ADMA)
• Metal matrix proteasis (MMP-9)
• Oxidative status (per ox)
• Interleukin 18 (IL-18)
• Free fatty acids (FFA)
• Oxidised LDL (ox-LDL)
• Microvascular blood circulation measured with laser Doppler at 37 °C (LDF37)
• Microvascular blood circulation measured with laser Doppler at 44 °C (LDF44)

Detailed Description

Phase III b Indication Type 2 Diabetes Trial Objectives 1) Primary objective: The primary objective of the study is to evaluate the postprandial time course of nitrotyrosine after injection of insulin glulisine compared with regular human insulin. 2) Secondary objectives: The secondary objectives are to evaluate the postprandial time course of blood glucose, insulin, intact proinsulin, asymmetric dimethylarginine (ADMA), metal matrix proteasis (MMP-9), free fatty acids (FFA), oxidised LDL (ox-LDL), oxidative status (per ox), IL-18 as well as postprandial time course of microvascular blood circulation measured with laserdopplerflux at 37 °C (LDF37) and 44 C (LDF44).

Efficacy Variables Primary efficacy variablePostprandial time course of nitrotyrosineSecondary efficacy variablePostprandial time course of glucose, insulin, intact proinsulin, ADMA, MMP-9, FFA, ox-LDL, per-ox, and IL-18 as well as postprandial time course of laserdopplerflux at 37 °C and 44 °C Safety Variables Incidence and frequency of adverse events and evaluation of safety laboratory parameters Medication/Dosage Insulin glulisine, dose 0.10 U/kg and Regular Human Insulin, dose 0.10 U/kg Study Duration Duration of study participation for one patient: 5 - 43 days Overall duration of the study: 6 months Design Single-centre, open label, randomized, 2-way-crossover trial Population Male and female type 2 diabetic patients between 40 and 70 years with HbA1c between 6.5 % and 9.9 % and treated with sulfonyurea alone or in combination with Metformin in a stable dosage within the last 3 months Sample Size N = 15

Conditions

Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

One Day Treatment with Insulin Glulisine

Group Type: EXPERIMENTAL

Insulin Glulisine

Intervention Type: DRUG

100 IU/ml, 0.10 U/kg immediately before ingestion of a standardised liquid meal

2

One day Treatment with Human insulin

Group Type: ACTIVE_COMPARATOR

Insulin

Intervention Type: DRUG

100 IU/ml, 0.10 U/kg 15 Minutes before ingestion of a standardised liquid meal

Interventions

Insulin Glulisine

100 IU/ml, 0.10 U/kg immediately before ingestion of a standardised liquid meal

Intervention Type: DRUG

Insulin

100 IU/ml, 0.10 U/kg 15 Minutes before ingestion of a standardised liquid meal

Intervention Type: DRUG

Other Intervention Names

Apidra; Insuman

Eligibility Criteria

Inclusion Criteria

1. Type 2 Diabetes mellitus according to the ADA criteria

2. HbA1c between 6.5 % and 9.9 %

3. Monotherapy with sulfonylurea or combined with Metformin in a stable dosage within the last 3 months

4. Age between 40 and 70 years

5. BMI < 40

Exclusion Criteria

1. Type 1 Diabetes mellitus

2. Pre-Treatment with insulin within the last 6 months prior to screening

3. Treatment with glitazones within the last 6 months prior to screening

4. Pre-Treatment with PPARy-agonists, glinides or glucosidase inhibitors within the last 4 weeks prior to screening

5. Untreated hypertension stage II-III according to WHO criteria

6. Planned or anticipated change in antidiabetic and/or concomitant medication during study participation

7. Total Cholesterol > 300 mg/dl (anamnestically)

8. Hypokalemia (K < 3.5 mmol /l)

9. Major micro- or macrovascular complications as judged by the investigator

10. Tobacco use within the last 12 months prior to screening

11. Drugs with major impact on endothelial function like nitrates etc.

12. History of drug or alcohol abuse within the last five years prior to screening

13. Anamnestic history of hypersensitivity to the study drugs or to drugs with similar chemical structures

14. History of severe or multiple allergies

15. Treatment with any other investigational drug within 3 months prior to screening

16. Progressive fatal disease

17. History of significant cardiovascular, respiratory, gastrointestinal, hepatic (ALAT and/or ASAT > 3 times the normal reference range), renal (creatinine > 1.1 mg/dL in women, > 1.5 mg/dL in men), neurological, psychiatric and/or haematological disease as judged by the investigator

18. Pregnancy or breast feeding

19. Sexually active women of childbearing potential not consistently and correctly practicing birth control by implants, injectables, combined oral contraceptives, hormonal intrauterine devices (IUDs), sexual abstinence or vasectomised partner

20. Lack of compliance or other similar reason, that according to investigator, precludes satisfactory participation in the study

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

IKFE Institute for Clinical Research and Development

OTHER

Sponsor Role: lead

Principal Investigators

Thomas A Forst, Prof, MD

Role: PRINCIPAL_INVESTIGATOR

Institute for Clinical Research and Development

Locations

Ikfe

Mainz, Rhineland-Palatinate, Germany

Countries

Germany

Other Identifiers

EudraCT Number 2006-005127-42

Identifier Type: -

Identifier Source: secondary_id

APIDR_L_01896

Identifier Type: -

Identifier Source: org_study_id