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

Primary Purpose

Type 2 Diabetes Mellitus

Status
Unknown status
Phase
Phase 4
Locations
Germany
Study Type
Interventional
Intervention
Insulin glulisine
Insulin aspart
Regular human insulin
Sponsored by
ikfe-CRO GmbH
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type 2 Diabetes Mellitus

Eligibility Criteria

30 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • ife GmbH, Clinic

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Active Comparator

Arm Label

Insulin Glulisine: bolus injections before each main meal

Insulin Aspart: bolus injections before each main meal

Regular human insulin:bolus injections before each main meal

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Nitrotyrosine
The difference in the percent increase of the oxidative stress biomarker nitrotyrosine after stimulation with a standardized meal

Secondary Outcome Measures

Skin blood flow
Change in skin blood flow during stimulation by a standardized meal
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
Insulin
Change in Insulin and the ratio from baseline to endpoint
HbA1c
Blood glucose control: Change during test meal, HbA1c and FBG from baseline to endpoint
Fasting blood glucose
Blood glucose control: Change during test meal, HbA1c and FBG from baseline to endpoint
Hypoglycemic events
Incidence of hypoglycemia from baseline to endpoint
intact Proinsulin
Change in intact Proinsulin and the ratio from baseline to endpoint

Full Information

First Posted
August 15, 2011
Last Updated
March 2, 2012
Sponsor
ikfe-CRO GmbH
Collaborators
IKFE Institute for Clinical Research and Development
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1. Study Identification

Unique Protocol Identification Number
NCT01417897
Brief Title
Human Insulin Analogs: Evaluation of Inflammatory mRNA Expression of Macrophages and Endothelial Function of Short-acting Insulin - HERMES Pilot Study
Acronym
HERMES
Official Title
Human Insulin Analogs: Evaluation of Inflammatory mRNA Expression of Macrophages and Endothelial Function of Short-acting Insulin - HERMES Pilot Study
Study Type
Interventional

2. Study Status

Record Verification Date
March 2012
Overall Recruitment Status
Unknown status
Study Start Date
September 2011 (undefined)
Primary Completion Date
May 2012 (Anticipated)
Study Completion Date
May 2012 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
ikfe-CRO GmbH
Collaborators
IKFE Institute for Clinical Research and Development

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes Mellitus

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Insulin Glulisine: bolus injections before each main meal
Arm Type
Experimental
Arm Description
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.
Arm Title
Insulin Aspart: bolus injections before each main meal
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Regular human insulin:bolus injections before each main meal
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Insulin glulisine
Other Intervention Name(s)
Apidra
Intervention Description
Dosage will be pro re nata. Patients should aim an blood glucose level of 2h ppBG ≤ 135 mg/dL.
Intervention Type
Drug
Intervention Name(s)
Insulin aspart
Other Intervention Name(s)
NovoRapid
Intervention Description
Dosage will be pro re nata. Patients should aim an blood glucose level of 2h ppBG ≤ 135 mg/dL.
Intervention Type
Drug
Intervention Name(s)
Regular human insulin
Other Intervention Name(s)
InsumanRapid
Intervention Description
Dosage will be pro re nata. Patients should aim an blood glucose level of 2h ppBG ≤ 135 mg/dL.
Primary Outcome Measure Information:
Title
Nitrotyrosine
Description
The difference in the percent increase of the oxidative stress biomarker nitrotyrosine after stimulation with a standardized meal
Time Frame
Baseline, after 10 weeks, after 24 weeks
Secondary Outcome Measure Information:
Title
Skin blood flow
Description
Change in skin blood flow during stimulation by a standardized meal
Time Frame
Baseline, after 10 weeks, after 24 weeks
Title
mRNA expression of proinflammatory cytokines (MAPK/eNOS, adiponectin, hsCRP, MMP-9)
Description
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
Time Frame
Baseline, after 10 weeks, after 24 weeks
Title
Insulin
Description
Change in Insulin and the ratio from baseline to endpoint
Time Frame
Baseline, after 10 weeks, after 24 weeks
Title
HbA1c
Description
Blood glucose control: Change during test meal, HbA1c and FBG from baseline to endpoint
Time Frame
Baseline, after 10 weeks, after 24 weeks
Title
Fasting blood glucose
Description
Blood glucose control: Change during test meal, HbA1c and FBG from baseline to endpoint
Time Frame
Baseline, after 10 weeks, after 24 weeks
Title
Hypoglycemic events
Description
Incidence of hypoglycemia from baseline to endpoint
Time Frame
Baseline, after 10 weeks, after 24 weeks
Title
intact Proinsulin
Description
Change in intact Proinsulin and the ratio from baseline to endpoint
Time Frame
Baseline, after 10 weeks, after 24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
ife GmbH, Clinic
City
Mainz
State/Province
Rhineland-Palatinate
ZIP/Postal Code
55116
Country
Germany

12. IPD Sharing Statement

Learn more about this trial

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

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