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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
IKFE Institute for Clinical Research and Development
Information provided by (Responsible Party):
Marcus Borchert, ikfe-CRO GmbH
ClinicalTrials.gov Identifier:
NCT01417897
First received: August 15, 2011
Last updated: March 2, 2012
Last verified: March 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Type 2 Diabetes Mellitus
 Drug: Insulin glulisine
Drug: Insulin aspart
Drug: Regular human insulin
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Human Insulin Analogs: Evaluation of Inflammatory mRNA Expression of Macrophages and Endothelial Function of Short-acting Insulin - HERMES Pilot Study

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by ikfe-CRO GmbH:

Primary Outcome Measures:
  • Nitrotyrosine [ Time Frame: Baseline, after 10 weeks, after 24 weeks ] [ Designated as safety issue: No ]
    The difference in the percent increase of the oxidative stress biomarker nitrotyrosine after stimulation with a standardized meal


Secondary Outcome Measures:
  • Skin blood flow [ Time Frame: Baseline, after 10 weeks, after 24 weeks ] [ Designated as safety issue: No ]
    Change in skin blood flow during stimulation by a standardized meal

  • mRNA expression of proinflammatory cytokines (MAPK/eNOS, adiponectin, hsCRP, MMP-9) [ Time Frame: Baseline, after 10 weeks, after 24 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, after 10 weeks, after 24 weeks ] [ Designated as safety issue: No ]
    Change in Insulin and the ratio from baseline to endpoint

  • HbA1c [ Time Frame: Baseline, after 10 weeks, after 24 weeks ] [ Designated as safety issue: No ]
    Blood glucose control: Change during test meal, HbA1c and FBG from baseline to endpoint

  • Fasting blood glucose [ Time Frame: Baseline, after 10 weeks, after 24 weeks ] [ Designated as safety issue: No ]
    Blood glucose control: Change during test meal, HbA1c and FBG from baseline to endpoint

  • Hypoglycemic events [ Time Frame: Baseline, after 10 weeks, after 24 weeks ] [ Designated as safety issue: Yes ]
    Incidence of hypoglycemia from baseline to endpoint

  • intact Proinsulin [ Time Frame: Baseline, after 10 weeks, after 24 weeks ] [ Designated as safety issue: No ]
    Change in intact Proinsulin and the ratio from baseline to endpoint


Estimated Enrollment: 12
Study Start Date: September 2011
Estimated Study Completion Date: May 2012
Estimated Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: InsumanRapid

  Eligibility

Ages Eligible for Study:   30 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01417897

Locations
Germany
ife GmbH, Clinic
Mainz, Rhineland-Palatinate, Germany, 55116
Sponsors and Collaborators
ikfe-CRO GmbH
IKFE Institute for Clinical Research and Development
  More Information

No publications provided

Responsible Party: Marcus Borchert, Thomas Forst, MD PhD, ikfe GmbH, Clinic, ikfe-CRO GmbH
ClinicalTrials.gov Identifier: NCT01417897     History of Changes
Other Study ID Numbers: APIDR_L_05719
Study First Received: August 15, 2011
Last Updated: March 2, 2012
Health Authority: Germany: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin aspart
 Insulin glulisine
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 19, 2013