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Establishing Cardiovascular Biomarkers to Define Preferred Lantus® Use

Phase 4
Conditions
Insulin-requiring Type 2 Diabetes Mellitus
Interventions
Registration Number
NCT01500850
Lead Sponsor
ikfe-CRO GmbH
Brief Summary

The aim of this study is to observe changes in cardiovascular biomarkers during treatment with Lantus in patients with Type 2 Diabetes mellitus.

Detailed Description

* Phase IV

* Indication: Diabetes mellitus Type 2

* Primary objective:

To compare fasting intact proinsulin secretion at the beginning and after a 24 week treatment period.

- Secondary objectives: To evaluate changes in the parameters

* insulin,

* glucose,

* intact proinsulin (after a glucose challenge),

* hsCRP,

* adiponectin,

* MMP-9,

* HbA1c,

* weight

after 24 weeks of treatment.

To investigate the changes of

* glucose,

* intact proinsulin,

* hsCRP,

* adiponectin,

* HbA1c

* weight

between visit 2 (baseline), visit 6 (12 weeks) and visit 8 (final visit after 24 weeks).

To investigate the number of patients with normal values for parameters hsCRP, adiponectin, and intact proinsulin after 24 weeks of treatment (responder rates).

-Primary efficacy variable: Fasting intact proinsulin concentration at timepoint Visit 2 (Baseline) and Visit 8 (after 24 week treatment)

-Secondary efficacy variables: All secondary parameters will be assessed after 24 weeks of treatment and compared versus baseline assessment.

* Weight

* hsCRP

* Adiponectin

* MMP-9

* OGTT parameters (insulin, intact proinsulin, glucose at time point 0, 60 and 120 minutes after 24 weeks

* HOMA-IR score

* HbA1c

Additionally the following parameters will be assessed at visit 6 and will be compared with visit 2 and visit 8:

* Weight

* hsCRP

* Adiponectin

* Fasting intact Proinsulin

* Glucose

* HbA1c

* Safety Variables:

* Adverse Events

* Hypoglycaemic events

Medication/Dosage:

Insulin glargine, dose individually adapted to reach treatment goal (FBG ≤ 100 mg/dL)NPH Insulin, dose individually adapted to reach treatment goal (FBG ≤ 100 mg/dL)Insulin glulisine, dose individually adapted to reach treatment goal (FBG ≤ 100 mg/dL)Human Insulin, dose individually adapted to reach treatment goal (FBG ≤ 100 mg/dL)

-Study Duration: Duration of study participation for one patient is approximately 26 weeks. Overall total duration of the study is approximately 10 months.

Design:

This is a randomized in four arms, open-label, multi-center study. Population Patients with Type 2 Diabetes mellitus, Sample Size n = 60 (15 per arm)

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
60
Inclusion Criteria
  • Give written informed consent.
  • Patient consents that his/her family physician/diabetologist will be informed of trial participation
  • Type-2 diabetes mellitus ≥ 1 year of diagnosis (male and female)
  • Experienced in self blood glucose measurement for ≥ 3 months.
  • HbA1c ≤ 9% and >6,5%
  • BMI > 30 kg/m²
  • Age ≥ 18 years
  • Waist circumference > 88 cm (female) and > 102 cm (male)
  • NPH insulin treatment plus 1 or 2 OAD (except TZD)
Exclusion Criteria
  • History of drug or alcohol abuse within the last five years prior to screening
  • Anamnestic 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
  • History of significant cardiovascular, respiratory, gastrointestinal, 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
  • Treatment with GLP1-analog or Thiazolidinediones (TZD)
  • hsCRP > 10 mg/l (by rapid test at screening visit).
  • Lack of compliance or other similar reason that, according to investigator, precludes satisfactory participation in the study
  • Type 1 Diabetes mellitus
  • Patients already treated with intensified conventional insulin therapy.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
NPH insulin + insulin glulisinenph insulinPatients will be randomized to be treated with NPH insulin + Insulin Glulisine for 24 weeks.
Insulin glargine + insulin glulisineInsulin GlarginePatients will be randomized to be treated with insulin glargine + insulin glulisine for 24 weeks.
Insulin glargine + insulin glulisineInsulin glulisinePatients will be randomized to be treated with insulin glargine + insulin glulisine for 24 weeks.
NPH insulin + human insulinhuman insulinPatients will be randomized to be treated with NPH insulin + human insulin for 24 weeks.
NPH insulin + insulin glulisineInsulin glulisinePatients will be randomized to be treated with NPH insulin + Insulin Glulisine for 24 weeks.
Insulin Glargine + Human insulinhuman insulinPatients will be randomized to be treated with insulin glargine + human insulin for 24 weeks.
Insulin Glargine + Human insulinInsulin GlarginePatients will be randomized to be treated with insulin glargine + human insulin for 24 weeks.
Primary Outcome Measures
NameTimeMethod
Fasting Intact ProinsulinChange from baseline at 24 weeks

The difference of fasting intact proinsulin after 24 weeks of treatment compared to baseline.

Secondary Outcome Measures
NameTimeMethod
WeightAfter 12 weeks of treatment compared to baseline and to 24 weeks of treatment.

To evaluate changes of weight after 12 weeks of treatment compared to baseline and compared to 24 weeks.

hsCRPAfter 12 weeks of treatment compared to baseline and to 24 weeks of treatment.

To evaluate changes of hsCRP after 12 weeks of treatment compared to baseline and compared to 24 weeks.

AdiponectinAfter 12 weeks of treatment compared to baseline and to 24 weeks of treatment.

To evaluate changes of adiponectin after 12 weeks of treatment compared to baseline and compared to 24 weeks.

MMP-9Baseline and after 24 weeks of treatment.

To evaluate changes of MMP-9 after 24 weeks of treatment compared to baseline.

OGTT parameters (insulin, intact proinsulin, glucose at time point 0, 60 and 120 minutes after 24 weeksBaseline and after 24 weeks of treatment.

To evaluate changes of OGTT parameters (insulin, intact proinsulin, glucose at time point 0, 60 and 120 minutes) after 24 weeks of treatment compared to baseline.

HOMA-IR scoreBaseline and after 24 weeks of treatment.

To evaluate changes of HOMA-IR score after 24 weeks of treatment compared to baseline.

HbA1cAfter 12 weeks of treatment compared to baseline and to 24 weeks of treatment.

To evaluate changes of HbA1c after 12 weeks of treatment compared to baseline and compared to 24 weeks.

Fasting intact ProinsulinAfter 12 weeks of treatment compared to baseline and to 24 weeks of treatment.

To evaluate changes of fasting intact proinsulin after 12 weeks of treatment compared to baseline and compared to 24 weeks.

GlucoseAfter 12 weeks of treatment compared to baseline and to 24 weeks of treatment.

To evaluate changes of Glucose after 12 weeks of treatment compared to baseline and compared to 24 weeks.

Responder rateAfter 24 weeks of treatment compared to baseline.

To investigate the number of patients with normal values for parameters hsCRP, adiponectin, and intact proinsulin after 24 weeks of treatment (responder rates).

Hypoglycemic events.Baseline up to 24 weeks.

Hypoglycemic events defined as blood glucose below 63 mg/dl.

Trial Locations

Locations (1)

ikfe GmbH

🇩🇪

Mainz, Rheinland-Pfalz, Germany

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