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

Type 2 Diabetes Mellitus Clinical Trial

— HERMES  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01417897
• Other study ID #: APIDR_L_05719
• Status: Active, not recruiting
• Phase: Phase 4
• First received: August 15, 2011
• Last updated: March 2, 2012
• Start date: September 2011
• Est. completion date: May 2012

Study information

• Verified date: March 2012
• Source: ikfe-CRO GmbH
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Ethics CommissionGermany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 12
• Est. completion date: May 2012
• Est. primary completion date: May 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 75 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Insulin glulisine
Dosage will be pro re nata. Patients should aim an blood glucose level of 2h ppBG = 135 mg/dL.
• Insulin aspart
Dosage will be pro re nata. Patients should aim an blood glucose level of 2h ppBG = 135 mg/dL.
• Regular human insulin
Dosage will be pro re nata. Patients should aim an blood glucose level of 2h ppBG = 135 mg/dL.

Locations

Country	Name	City	State
Germany	ife GmbH, Clinic	Mainz	Rhineland-Palatinate

Sponsors (2)

Lead Sponsor	Collaborator
ikfe-CRO GmbH	IKFE Institute for Clinical Research and Development

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Skin blood flow	Change in skin blood flow during stimulation by a standardized meal	Baseline, after 10 weeks, after 24 weeks	No
Secondary	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	No
Secondary	Insulin	Change in Insulin and the ratio from baseline to endpoint	Baseline, after 10 weeks, after 24 weeks	No
Secondary	HbA1c	Blood glucose control: Change during test meal, HbA1c and FBG from baseline to endpoint	Baseline, after 10 weeks, after 24 weeks	No
Secondary	Fasting blood glucose	Blood glucose control: Change during test meal, HbA1c and FBG from baseline to endpoint	Baseline, after 10 weeks, after 24 weeks	No
Secondary	Hypoglycemic events	Incidence of hypoglycemia from baseline to endpoint	Baseline, after 10 weeks, after 24 weeks	Yes
Secondary	intact Proinsulin	Change in intact Proinsulin and the ratio from baseline to endpoint	Baseline, after 10 weeks, after 24 weeks	No