Establishing Cardiovascular Biomarkers to Define Preferred Lantus® Use

Establishing Cardiovascular Biomarkers to Define Preferred Lantus® Use.

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

Study Overview

• Status: Unknown
• Conditions: Insulin-requiring Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: nph insulin; Drug: Insulin glulisine; Drug: human insulin; Drug: Insulin Glargine

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)

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Andreas Pfützner, Professor; Phone Number: 20 00496131-57636-0; Email: andreasp@ikfe.de
• Study Contact Backup: Name: Thomas Forst, Professor; Phone Number: 16 00496131-57636-0; Email: thomasf@ikfe.de

Study Locations

• Germany
  • Rheinland-Pfalz
    • Mainz, Rheinland-Pfalz, Germany, 55116
      • Recruiting
      • IKFE GmbH
      • Contact: Thomas Forst, MD; Phone Number: 16 +49(0) 6131-576 36 -40; Email: thomasf@ikfe.de
      • Contact: Daniela Sachsenheimer, MD; Phone Number: 46 +49(0) 6131-576 36 40; Email: danielas@ikfe.de
      • Sub-Investigator: Stephan Diessel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: NPH insulin + insulin glulisine; Patients will be randomized to be treated with NPH insulin + Insulin Glulisine for 24 weeks.	Drug: nph insulin; Dosage will be pro re nata. Patients should aim an blood glucose level of ≤ 100 mg/dL.; Other Names: Insuman Basal; Drug: Insulin glulisine; Dosage will be pro re nata. Patients should aim an blood glucose level of ≤ 100 mg/dL. Insulin glulisine: bolus injections before each main meal; Other Names: Apidra
ACTIVE_COMPARATOR: NPH insulin + human insulin; Patients will be randomized to be treated with NPH insulin + human insulin for 24 weeks.	Drug: human insulin; Dosage will be pro re nata. Patients should aim an blood glucose level of ≤ 100 mg/dL. human insulin: bolus injections before each main meal; Other Names: Insuman Rapid
EXPERIMENTAL: Insulin glargine + insulin glulisine; Patients will be randomized to be treated with insulin glargine + insulin glulisine for 24 weeks.	Drug: Insulin glulisine; Dosage will be pro re nata. Patients should aim an blood glucose level of ≤ 100 mg/dL. Insulin glulisine: bolus injections before each main meal; Other Names: Apidra; Drug: Insulin Glargine; Dosage will be pro re nata. Patients should aim an blood glucose level of ≤ 100 mg/dL.; Other Names: Lantus
EXPERIMENTAL: Insulin Glargine + Human insulin; Patients will be randomized to be treated with insulin glargine + human insulin for 24 weeks.	Drug: human insulin; Dosage will be pro re nata. Patients should aim an blood glucose level of ≤ 100 mg/dL. human insulin: bolus injections before each main meal; Other Names: Insuman Rapid; Drug: Insulin Glargine; Dosage will be pro re nata. Patients should aim an blood glucose level of ≤ 100 mg/dL.; Other Names: Lantus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fasting Intact Proinsulin	The difference of fasting intact proinsulin after 24 weeks of treatment compared to baseline.	Change from baseline at 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight	To evaluate the changes of weight after 24 weeks of treatment compared to baseline.	Baseline and after 24 weeks of treatment.
hsCRP	To evaluate changes of hsCRP after 24 weeks of treatment compared to baseline.	Baseline and after 24 weeks of treatment.
Adiponectin	To evaluate changes of adiponectin after 24 weeks of treatment compared to baseline.	Baseline and after 24 weeks of treatment.
MMP-9	To evaluate changes of MMP-9 after 24 weeks of treatment compared to baseline.	Baseline and after 24 weeks of treatment.
OGTT parameters (insulin, intact proinsulin, glucose at time point 0, 60 and 120 minutes after 24 weeks	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.	Baseline and after 24 weeks of treatment.
HOMA-IR score	To evaluate changes of HOMA-IR score after 24 weeks of treatment compared to baseline.	Baseline and after 24 weeks of treatment.
HbA1c	To evaluate changes of HbA1C after 24 weeks of treatment compared to baseline.	Baseline and after 24 weeks of treatment.
Weight	To evaluate changes of weight after 12 weeks of treatment compared to baseline and compared to 24 weeks.	After 12 weeks of treatment compared to baseline and to 24 weeks of treatment.
hsCRP	To evaluate changes of hsCRP after 12 weeks of treatment compared to baseline and compared to 24 weeks.	After 12 weeks of treatment compared to baseline and to 24 weeks of treatment.
Adiponectin	To evaluate changes of adiponectin after 12 weeks of treatment compared to baseline and compared to 24 weeks.	After 12 weeks of treatment compared to baseline and to 24 weeks of treatment.
Fasting intact Proinsulin	To evaluate changes of fasting intact proinsulin after 12 weeks of treatment compared to baseline and compared to 24 weeks.	After 12 weeks of treatment compared to baseline and to 24 weeks of treatment.
Glucose	To evaluate changes of Glucose after 12 weeks of treatment compared to baseline and compared to 24 weeks.	After 12 weeks of treatment compared to baseline and to 24 weeks of treatment.
HbA1c	To evaluate changes of HbA1c after 12 weeks of treatment compared to baseline and compared to 24 weeks.	After 12 weeks of treatment compared to baseline and to 24 weeks of treatment.
Responder rate	To investigate the number of patients with normal values for parameters hsCRP, adiponectin, and intact proinsulin after 24 weeks of treatment (responder rates).	After 24 weeks of treatment compared to baseline.
Hypoglycemic events.	Hypoglycemic events defined as blood glucose below 63 mg/dl.	Baseline up to 24 weeks.

Collaborators and Investigators

• Sponsor: ikfe-CRO GmbH
• Collaborators: IKFE Institute for Clinical Research and Development
• Investigators: Principal Investigator: Andreas Pfützner, Professor, IKFE GmbH

Publications and helpful links

General Publications

• Semlitsch T, Engler J, Siebenhofer A, Jeitler K, Berghold A, Horvath K. (Ultra-)long-acting insulin analogues versus NPH insulin (human isophane insulin) for adults with type 2 diabetes mellitus. Cochrane Database Syst Rev. 2020 Nov 9;11(11):CD005613. doi: 10.1002/14651858.CD005613.pub4.

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (ANTICIPATED): October 1, 2012
• Study Completion (ANTICIPATED): October 1, 2012

Study Registration Dates

• First Submitted: December 5, 2011
• First Submitted That Met QC Criteria: December 23, 2011
• First Posted (ESTIMATE): December 29, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): December 29, 2011
• Last Update Submitted That Met QC Criteria: December 23, 2011
• Last Verified: December 1, 2011

More Information

Terms related to this study

• Keywords: cardiovascular risk; Type 2 Diabetes mellitus; Insulin Glargine; NPH insulin; cardiovascular biomarkers; hsCRP, adiponectin; intact proinsulin
• 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 Glargine; Insulin glulisine; Insulin, Isophane; Isophane Insulin, Human; Isophane insulin, beef
• Other Study ID Numbers: Lantu_L_05720