Insulin-requiring Type 2 Diabetes Mellitus
Conditions
Keywords
Type 2 Diabetes mellitus, NPH insulin, Insulin Glargine, cardiovascular biomarkers, hsCRP, adiponectin, intact proinsulin, cardiovascular risk
Brief summary
The aim of this study is to observe changes in cardiovascular biomarkers during treatment with Lantus in patients with Type 2 Diabetes mellitus.
Detailed description
* Phase IV * Indication: Diabetes mellitus Type 2 * Primary objective: To compare fasting intact proinsulin secretion at the beginning and after a 24 week treatment period. \- Secondary objectives: To evaluate changes in the parameters * insulin, * glucose, * intact proinsulin (after a glucose challenge), * hsCRP, * adiponectin, * MMP-9, * HbA1c, * weight after 24 weeks of treatment. To investigate the changes of * glucose, * intact proinsulin, * hsCRP, * adiponectin, * HbA1c * weight between visit 2 (baseline), visit 6 (12 weeks) and visit 8 (final visit after 24 weeks). To investigate the number of patients with normal values for parameters hsCRP, adiponectin, and intact proinsulin after 24 weeks of treatment (responder rates). -Primary efficacy variable: Fasting intact proinsulin concentration at timepoint Visit 2 (Baseline) and Visit 8 (after 24 week treatment) -Secondary efficacy variables: All secondary parameters will be assessed after 24 weeks of treatment and compared versus baseline assessment. * Weight * hsCRP * Adiponectin * MMP-9 * OGTT parameters (insulin, intact proinsulin, glucose at time point 0, 60 and 120 minutes after 24 weeks * HOMA-IR score * HbA1c Additionally the following parameters will be assessed at visit 6 and will be compared with visit 2 and visit 8: * Weight * hsCRP * Adiponectin * Fasting intact Proinsulin * Glucose * HbA1c * Safety Variables: * Adverse Events * Hypoglycaemic events Medication/Dosage: Insulin glargine, dose individually adapted to reach treatment goal (FBG ≤ 100 mg/dL)NPH Insulin, dose individually adapted to reach treatment goal (FBG ≤ 100 mg/dL)Insulin glulisine, dose individually adapted to reach treatment goal (FBG ≤ 100 mg/dL)Human Insulin, dose individually adapted to reach treatment goal (FBG ≤ 100 mg/dL) -Study Duration: Duration of study participation for one patient is approximately 26 weeks. Overall total duration of the study is approximately 10 months. Design: This is a randomized in four arms, open-label, multi-center study. Population Patients with Type 2 Diabetes mellitus, Sample Size n = 60 (15 per arm)
Interventions
DRUGnph insulin
Dosage will be pro re nata. Patients should aim an blood glucose level of ≤ 100 mg/dL.
DRUGhuman insulin
Dosage will be pro re nata. Patients should aim an blood glucose level of ≤ 100 mg/dL. human insulin: bolus injections before each main meal
DRUGInsulin Glargine
Dosage will be pro re nata. Patients should aim an blood glucose level of ≤ 100 mg/dL.
DRUGInsulin glulisine
Dosage will be pro re nata. Patients should aim an blood glucose level of ≤ 100 mg/dL. Insulin glulisine: bolus injections before each main meal
Sponsors
IKFE Institute for Clinical Research and Development
ikfe-CRO GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Give written informed consent. * Patient consents that his/her family physician/diabetologist will be informed of trial participation * Type-2 diabetes mellitus ≥ 1 year of diagnosis (male and female) * Experienced in self blood glucose measurement for ≥ 3 months. * HbA1c ≤ 9% and \>6,5% * BMI \> 30 kg/m² * Age ≥ 18 years * Waist circumference \> 88 cm (female) and \> 102 cm (male) * NPH insulin treatment plus 1 or 2 OAD (except TZD)
Exclusion criteria
* History of drug or alcohol abuse within the last five years prior to screening * Anamnestic history of hypersensitivity to the study drugs (or any component of the study drug) 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 \>1.6 mg/dl in men), neurological, psychiatric and/or hematological disease as judged by the investigator * Pregnant or lactating women * 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 vasectomized partner * Treatment with GLP1-analog or Thiazolidinediones (TZD) * hsCRP \> 10 mg/l (by rapid test at screening visit). * Lack of compliance or other similar reason that, according to investigator, precludes satisfactory participation in the study * Type 1 Diabetes mellitus * Patients already treated with intensified conventional insulin therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fasting Intact Proinsulin | Change from baseline at 24 weeks | The difference of fasting intact proinsulin after 24 weeks of treatment compared to baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| hsCRP | Baseline and after 24 weeks of treatment. | To evaluate changes of hsCRP after 24 weeks of treatment compared to baseline. |
| Adiponectin | Baseline and after 24 weeks of treatment. | To evaluate changes of adiponectin after 24 weeks of treatment compared to baseline. |
| MMP-9 | Baseline and after 24 weeks of treatment. | To evaluate changes of MMP-9 after 24 weeks of treatment compared to baseline. |
| OGTT parameters (insulin, intact proinsulin, glucose at time point 0, 60 and 120 minutes after 24 weeks | Baseline and after 24 weeks of treatment. | To evaluate changes of OGTT parameters (insulin, intact proinsulin, glucose at time point 0, 60 and 120 minutes) after 24 weeks of treatment compared to baseline. |
| HOMA-IR score | Baseline and after 24 weeks of treatment. | To evaluate changes of HOMA-IR score after 24 weeks of treatment compared to baseline. |
| Weight | Baseline and after 24 weeks of treatment. | To evaluate the changes of weight after 24 weeks of treatment compared to baseline. |
| Fasting intact Proinsulin | After 12 weeks of treatment compared to baseline and to 24 weeks of treatment. | To evaluate changes of fasting intact proinsulin after 12 weeks of treatment compared to baseline and compared to 24 weeks. |
| Glucose | After 12 weeks of treatment compared to baseline and to 24 weeks of treatment. | To evaluate changes of Glucose after 12 weeks of treatment compared to baseline and compared to 24 weeks. |
| Responder rate | After 24 weeks of treatment compared to baseline. | To investigate the number of patients with normal values for parameters hsCRP, adiponectin, and intact proinsulin after 24 weeks of treatment (responder rates). |
| Hypoglycemic events. | Baseline up to 24 weeks. | Hypoglycemic events defined as blood glucose below 63 mg/dl. |
| HbA1c | Baseline and after 24 weeks of treatment. | To evaluate changes of HbA1C after 24 weeks of treatment compared to baseline. |
Countries
Germany
Contacts
Primary ContactAndreas Pfützner, Professor
Backup ContactThomas Forst, Professor
Outcome results
None listed