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

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.

Study Overview

• Status: Unknown
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Insulin glulisine; Drug: Insulin aspart; Drug: Regular human insulin

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Rhineland-Palatinate
    • Mainz, Rhineland-Palatinate, Germany, 55116
      • ife GmbH, Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Insulin Glulisine: bolus injections before each main meal; 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.	Drug: Insulin glulisine; Dosage will be pro re nata. Patients should aim an blood glucose level of 2h ppBG ≤ 135 mg/dL.; Other Names: Apidra
Active Comparator: Insulin Aspart: bolus injections before each main meal; 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.	Drug: Insulin aspart; Dosage will be pro re nata. Patients should aim an blood glucose level of 2h ppBG ≤ 135 mg/dL.; Other Names: NovoRapid
Active Comparator: Regular human insulin:bolus injections before each main meal; 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.	Drug: Regular human insulin; Dosage will be pro re nata. Patients should aim an blood glucose level of 2h ppBG ≤ 135 mg/dL.; Other Names: InsumanRapid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nitrotyrosine	The difference in the percent increase of the oxidative stress biomarker nitrotyrosine after stimulation with a standardized meal	Baseline, after 10 weeks, after 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Skin blood flow	Change in skin blood flow during stimulation by a standardized meal	Baseline, after 10 weeks, after 24 weeks
mRNA expression of proinflammatory cytokines (MAPK/eNOS, adiponectin, hsCRP, MMP-9)	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	Baseline, after 10 weeks, after 24 weeks
Insulin	Change in Insulin and the ratio from baseline to endpoint	Baseline, after 10 weeks, after 24 weeks
HbA1c	Blood glucose control: Change during test meal, HbA1c and FBG from baseline to endpoint	Baseline, after 10 weeks, after 24 weeks
Fasting blood glucose	Blood glucose control: Change during test meal, HbA1c and FBG from baseline to endpoint	Baseline, after 10 weeks, after 24 weeks
Hypoglycemic events	Incidence of hypoglycemia from baseline to endpoint	Baseline, after 10 weeks, after 24 weeks
intact Proinsulin	Change in intact Proinsulin and the ratio from baseline to endpoint	Baseline, after 10 weeks, after 24 weeks

Collaborators and Investigators

• Sponsor: ikfe-CRO GmbH
• Collaborators: IKFE Institute for Clinical Research and Development

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Anticipated): May 1, 2012
• Study Completion (Anticipated): May 1, 2012

Study Registration Dates

• First Submitted: August 15, 2011
• First Submitted That Met QC Criteria: August 15, 2011
• First Posted (Estimate): August 16, 2011

Study Record Updates

• Last Update Posted (Estimate): March 5, 2012
• Last Update Submitted That Met QC Criteria: March 2, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Aspart; Insulin glulisine
• Other Study ID Numbers: APIDR_L_05719