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

Overview[ - collapse ][ - ]

Purpose 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.
ConditionType 2 Diabetic Patients
Insufficient Metabolic Control
OAD Treatment
InterventionDrug: Insulin Glargin
Drug: NPH insulin
Drug: Insulin detemir
Drug: metformin
PhasePhase 4
Sponsorikfe-CRO GmbH
Responsible Partyikfe-CRO GmbH
ClinicalTrials.gov IdentifierNCT00941148
First ReceivedJuly 16, 2009
Last UpdatedJuly 16, 2009
Last verifiedJuly 2009

Tracking Information[ + expand ][ + ]

First Received DateJuly 16, 2009
Last Updated DateJuly 16, 2009
Start DateApril 2008
Estimated Primary Completion DateMarch 2009
Current Primary Outcome Measurespostprandial dynamics of intact proinsulin secretion after standardized test meals (AUC for two hours after dinner) [Time Frame: 12 +/- 2 weeks] [Designated as safety issue: No]
Current Secondary Outcome Measures
  • AUC for intact proinsulin levels for two hours after a standardized test meal (breakfast and lunch) [Time Frame: 12 +/- 2 weeks] [Designated as safety issue: No]
  • increase of intact proinsulin after breakfast (BF), lunch (LU) and dinner (DI) [Time Frame: 12 +/- 2 weeks] [Designated as safety issue: No]
  • Ratio of exogenous insulin vs. endogenous insulin (measurements of glargine, NPH Insulin, detemir and human insulin levels) [Time Frame: 12 +/- 2 weeks] [Designated as safety issue: No]
  • Postprandial endothelial function measured as postischaemic response in LDF measurements (after BF, LU, DI) [Time Frame: 12 +/- 2 weeks] [Designated as safety issue: No]
  • Postprandial change in and AUC for hs CRP (after BF, LU, DI) [Time Frame: 12 +/- 2 weeks] [Designated as safety issue: No]
  • Postprandial change in and AUC for ADMA (after BF, LU, DI) [Time Frame: 12 +/- 2 weeks] [Designated as safety issue: No]
  • Postprandial increase in and AUC for glucose levels (after BF, LU, DI) [Time Frame: 12 +/- 2 weeks] [Designated as safety issue: No]
  • Changes in FBG [Time Frame: 12 +/- 2 weeks] [Designated as safety issue: No]
  • Changes in 8-point BG profiles [Time Frame: 12 +/- 2 weeks] [Designated as safety issue: No]
  • Percentage of patients reaching the treatment goal [Time Frame: 12 +/- 2 weeks] [Designated as safety issue: No]
  • Insulin dosage per kg body weight to reach treatment goal [Time Frame: 12 +/- 2 weeks] [Designated as safety issue: No]

Descriptive Information[ + expand ][ + ]

Brief TitleBeta-Cell Function of Insulin Glargine Compared to Neutral Protamine Hagedorn (NPH) Insuline and to Insulin Detemir in Combination With Metformin
Official TitleImpact 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
Brief 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.
Detailed DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 4
Study DesignAllocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition
  • Type 2 Diabetic Patients
  • Insufficient Metabolic Control
  • OAD Treatment
InterventionDrug: Insulin Glargin
Drug: NPH insulin
Drug: Insulin detemir
Drug: metformin
metformin (2000 mg/day)
Study Arm (s)
  • Active Comparator: Insulin glargine
    Insulin glargine, dose individually adapted to reach treatment goal (FBG < 100 mg/dL)
  • Active Comparator: NPH Insulin
    NPH Insulin, dose individually adapted to reach treatment goal (FBG < 100 mg/dL)
  • Active Comparator: Insulin detemir
    Insulin detemir, dose individually adapted to reach treatment goal (FBG < 100 mg/dL)

Recruitment Information[ + expand ][ + ]

Recruitment StatusCompleted
Estimated Enrollment30
Estimated Completion DateMarch 2009
Estimated Primary Completion DateMarch 2009
Eligibility Criteria
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
GenderBoth
Ages40 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesGermany

Administrative Information[ + expand ][ + ]

NCT Number NCT00941148
Other Study ID NumbersLANT_001
Has Data Monitoring CommitteeYes
Information Provided Byikfe-CRO GmbH
Study Sponsorikfe-CRO GmbH
CollaboratorsIKFE Institute for Clinical Research and Development
Investigators Not Provided
Verification DateJuly 2009

Locations[ + expand ][ + ]

ikfe GmbH, Clinic Department
Mainz, RLP, Germany, 55116