Human Insulin Analogs: Evaluation of Inflammatory mRNA Expression of Macrophages and Endothelial Function of Short-acting Insulin - HERMES Pilot Study

Phase 4

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Drug: Regular human insulin; Drug: Insulin glulisine; Drug: Insulin aspart

• Registration Number: NCT01417897
• Lead Sponsor: ikfe-CRO GmbH

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-08-15
• Study First Submitted QC: 2011-08-15
• Study First Posted: 2011-08-16
• Study Start: 2011-09
• Status Verified: 2012-03
• Last Update Submitted: 2012-03-02
• Last Update Posted: 2012-03-05
• Primary Completion: 2012-05
• Study Completion: 2012-05

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 12

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Regular human insulin:bolus injections before each main meal	Regular human insulin	Patients are already on an Insulin Glargine ± metformin therapy when they start the start and will them after randomization receive additionally regular human insulin bolus injections before each of the main meals.
Insulin Glulisine: bolus injections before each main meal	Insulin glulisine	Patients are already on an Insulin Glargine therapy when they start and will them after randomization receive additionally Insulin Glulisine bolus injections before each of the main meals.
Insulin Aspart: bolus injections before each main meal	Insulin aspart	Patients are already on an Insulin Glargine ± metformin therapy when they start the start and will them after randomization receive additionally Insulin Aspart bolus injections before each of the main meals.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Skin blood flow	Baseline, after 10 weeks, after 24 weeks	Change in skin blood flow during stimulation by a standardized meal
HbA1c	Baseline, after 10 weeks, after 24 weeks	Blood glucose control: Change during test meal, HbA1c and FBG from baseline to endpoint
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
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

Trial Locations

Locations (1)

ife GmbH, Clinic; 🇩🇪 Mainz, Rhineland-Palatinate, Germany