Establishing Cardiovascular Biomarkers to Define Preferred Lantus® Use

Insulin-requiring Type 2 Diabetes Mellitus Clinical Trial

Official title:

Establishing Cardiovascular Biomarkers to Define Preferred Lantus® Use.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01500850
• Other study ID #: Lantu_L_05720
• Status: Recruiting
• Phase: Phase 4
• First received: December 5, 2011
• Last updated: December 23, 2011
• Start date: October 2011
• Est. completion date: October 2012

Study information

• Verified date: December 2011
• Source: ikfe-CRO GmbH
• Contact: Andreas Pfützner, Professor
• Phone: 00496131-57636-0
• Email: andreasp[@]ikfe.de
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: October 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Insulin-requiring Type 2 Diabetes Mellitus

Intervention

Drug:
• nph insulin
Dosage will be pro re nata. Patients should aim an blood glucose level of = 100 mg/dL.
• 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
• Insulin Glargine
Dosage will be pro re nata. Patients should aim an blood glucose level of = 100 mg/dL.
• 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

Locations

Country	Name	City	State
Germany	ikfe GmbH	Mainz	Rheinland-Pfalz

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	Fasting Intact Proinsulin	The difference of fasting intact proinsulin after 24 weeks of treatment compared to baseline.	Change from baseline at 24 weeks	No
Secondary	Weight	To evaluate the changes of weight after 24 weeks of treatment compared to baseline.	Baseline and after 24 weeks of treatment.	No
Secondary	hsCRP	To evaluate changes of hsCRP after 24 weeks of treatment compared to baseline.	Baseline and after 24 weeks of treatment.	No
Secondary	Adiponectin	To evaluate changes of adiponectin after 24 weeks of treatment compared to baseline.	Baseline and after 24 weeks of treatment.	No
Secondary	MMP-9	To evaluate changes of MMP-9 after 24 weeks of treatment compared to baseline.	Baseline and after 24 weeks of treatment.	No
Secondary	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.	No
Secondary	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.	No
Secondary	HbA1c	To evaluate changes of HbA1C after 24 weeks of treatment compared to baseline.	Baseline and after 24 weeks of treatment.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	Hypoglycemic events.	Hypoglycemic events defined as blood glucose below 63 mg/dl.	Baseline up to 24 weeks.	Yes