Type 2 Diabetes Mellitus
Conditions
Brief summary
The planned HERMES study is to investigate and compare the effects of Insulin Glulisine, Insulin Aspart and regular human insulin on postprandial nitrotyrosine concentrations and several clinical and laboratory markers of postprandial endothelial cell function, sub-clinical inflammation and cardiovascular risk in patients with type 2 DM. The primary parameter in this study are the postprandial changes in the nitrotyrosine concentrations, a biomarker for oxidative stress. As vascular data on Insulin Glulisine vs. Insulin Aspart are missing, it is not possible to calculate sample size and statistical power. Therefore the goal of the HERMES-Pilot-Study is to generate preliminary data for statistical considerations and estimations on the probability of success of HERMES.
Interventions
DRUGInsulin glulisine
Dosage will be pro re nata. Patients should aim an blood glucose level of 2h ppBG ≤ 135 mg/dL.
DRUGInsulin aspart
Dosage will be pro re nata. Patients should aim an blood glucose level of 2h ppBG ≤ 135 mg/dL.
Dosage will be pro re nata. Patients should aim an blood glucose level of 2h ppBG ≤ 135 mg/dL.
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
30 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Type 2 diabetes mellitus * Stable BOT (basal oral therapy) with Insulin Glargine + ≥ 2 OHA (oral hypoglycemic agents except for TZD) for a minimum of three months before entering the study * HbA1c ≤ 8.5% * Age between 30 and 75 years inclusively * Body mass index ≤ 40 kg/m2 * Patient consents that his/her family physician will be informed of trial participation
Exclusion criteria
* Type 1 diabetes mellitus * Unspecific infection or inflammation (hsCRP \>10mg/L in POC test) * Use of thiazolidinediones within the last 3 months prior to study start * Retinopathy, hepatic or renal dysfunction or clinically relevant other major diseases * History of drug or alcohol abuse within the last five years prior to screening * 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 * 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 * Lack of compliance or other similar reason that, according to investigator, precludes satisfactory participation in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Nitrotyrosine | Baseline, after 10 weeks, after 24 weeks | The difference in the percent increase of the oxidative stress biomarker nitrotyrosine after stimulation with a standardized meal |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| mRNA expression of proinflammatory cytokines (MAPK/eNOS, adiponectin, hsCRP, MMP-9) | Baseline, after 10 weeks, after 24 weeks | Biomarkers of sub-clinical inflammation and cardiovascular risk: Change in Macrophage activation, MAPK/eNOS production levels, adiponectin and hsCRP (after test meal) from baseline to endpoint |
| Insulin | Baseline, after 10 weeks, after 24 weeks | Change in Insulin and the ratio from baseline to endpoint |
| HbA1c | Baseline, after 10 weeks, after 24 weeks | Blood glucose control: Change during test meal, HbA1c and FBG from baseline to endpoint |
| Skin blood flow | Baseline, after 10 weeks, after 24 weeks | Change in skin blood flow during stimulation by a standardized meal |
| Hypoglycemic events | Baseline, after 10 weeks, after 24 weeks | Incidence of hypoglycemia from baseline to endpoint |
| intact Proinsulin | Baseline, after 10 weeks, after 24 weeks | Change in intact Proinsulin and the ratio from baseline to endpoint |
| Fasting blood glucose | Baseline, after 10 weeks, after 24 weeks | Blood glucose control: Change during test meal, HbA1c and FBG from baseline to endpoint |
Countries
Germany
Outcome results
None listed