Beta-Cell Function of Insulin Glargine Compared to Neutral Protamine Hagedorn (NPH) Insuline and to Insulin Detemir in Combination With Metformin

Type 2 Diabetic Patients Clinical Trial

Official title:

Impact of Insulin (I.)Glargine Compared to NPH I. and to I. Detemir in Combination With Metformin on Prandial ß-cell Function and Overall Metabolic Control in Type 2 Diabetic Patients With Insufficient Metabolic Control During OAD Treatment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00941148
• Other study ID #: LANT_001
• Secondary ID: EudraCT Number:
• Status: Completed
• Phase: Phase 4
• First received: July 16, 2009
• Last updated: July 16, 2009
• Start date: April 2008
• Est. completion date: March 2009

Study information

• Verified date: July 2009
• Source: ikfe-CRO GmbH
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

The aim of the study is to show that treatment with Glargine will lead to an improvement in beta cell function especially within times of maximal beta cell stress occurring after a meal. For this reason three different standardized test meals (breakfast, lunch, dinner) will be performed and the postprandial secretion of intact proinsulin levels will be measured. These measurements will be performed with patients treated in combination with metformin and insulin glargine versus metformin plus NPH insulin (within the core study) and if significant difference is observed, with a third treatment arm with metformin plus insulin detemir.

Hypothesis is that the area under the curve (AUC) intact proinsulin levels within 2 hours after test meal dinner of metformin plus insulin glargin differs from AUC intact proinsulin levels of metformin plus NPH insulin.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: March 2009
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 75 Years

Eligibility

Inclusion Criteria:

• Type 2 Diabetes mellitus according to the ADA criteria

• HbA1c between 6.5% and 8.5%

• Individually optimized combination therapy with metformin in combination with sulfonylurea in a stable dosage within the last 3 months

• Age between 40 and 75 years

• Fasting intact proinsulin level > 7 pmol/Land < 20 pmol/Lat screening

Exclusion Criteria:

• Type 1 Diabetes mellitus

• Pre-Treatment with insulin within the last 3 months prior to screening

• Pre-Treatment with PPARy-agonists (glitazones) within the last 3 months prior to screening

• Major micro- or macrovascular complications as judged by the investigator

• BMI > 40 kg/m²

• Hypokalemia (K < 3.5 mmol /L)

• History of drug or alcohol abuse

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

• History of severe or multiple allergies

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

• Progressive fatal disease

• History of significant cardiovascular, respiratory, gastrointestinal, hepatic (ALAT and/or ASAT > 3 times the normal reference range), renal (creatinine > 1.3 mg/dL in women and > 1.7 mg/dL in men), neurological, psychiatric and/or haematological disease as judged by the investigator

• Pregnancy or breast feeding

• Sexually active women of childbearing potential not actively and consistently practicing birth control by using a medically accepted device or therapy

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Insufficient Metabolic Control
• OAD Treatment
• Type 2 Diabetic Patients

Intervention

Drug:
• Insulin Glargin

• NPH insulin

• Insulin detemir

• metformin
metformin (2000 mg/day)

Locations

Country	Name	City	State
Germany	ikfe GmbH, Clinic Department	Mainz	RLP

Sponsors (2)

Lead Sponsor	Collaborator
ikfe-CRO GmbH	IKFE Institute for Clinical Research and Development

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	postprandial dynamics of intact proinsulin secretion after standardized test meals (AUC for two hours after dinner)		12 +/- 2 weeks	No
Secondary	AUC for intact proinsulin levels for two hours after a standardized test meal (breakfast and lunch)		12 +/- 2 weeks	No
Secondary	increase of intact proinsulin after breakfast (BF), lunch (LU) and dinner (DI)		12 +/- 2 weeks	No
Secondary	Ratio of exogenous insulin vs. endogenous insulin (measurements of glargine, NPH Insulin, detemir and human insulin levels)		12 +/- 2 weeks	No
Secondary	Postprandial endothelial function measured as postischaemic response in LDF measurements (after BF, LU, DI)		12 +/- 2 weeks	No
Secondary	Postprandial change in and AUC for hs CRP (after BF, LU, DI)		12 +/- 2 weeks	No
Secondary	Postprandial change in and AUC for ADMA (after BF, LU, DI)		12 +/- 2 weeks	No
Secondary	Postprandial increase in and AUC for glucose levels (after BF, LU, DI)		12 +/- 2 weeks	No
Secondary	Changes in FBG		12 +/- 2 weeks	No
Secondary	Changes in 8-point BG profiles		12 +/- 2 weeks	No
Secondary	Percentage of patients reaching the treatment goal		12 +/- 2 weeks	No
Secondary	Insulin dosage per kg body weight to reach treatment goal		12 +/- 2 weeks	No