Clinical trial NCT01500850: Establishing Cardiovascular Biomarkers to Define Preferred Lantus® Use
Official title: Establishing Cardiovascular Biomarkers to Define Preferred Lantus® Use.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Insulin-requiring Type 2 Diabetes Mellitus
Keywords: Type 2 Diabetes mellitus
NPH insulin
Insulin Glargine
cardiovascular biomarkers
hsCRP, adiponectin
intact proinsulin
cardiovascular risk
Lead sponsor: ikfe-CRO GmbH
Sponsor class: INDUSTRY
Collaborators: name: IKFE Institute for Clinical Research and Development
First posted: 2011-12-29
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)

Eligibility criteria: 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.

Primary outcomes:
measure: Fasting Intact Proinsulin
timeFrame: Change from baseline at 24 weeks
Secondary outcomes:
measure: Weight
timeFrame: Baseline and after 24 weeks of treatment.
measure: hsCRP
timeFrame: Baseline and after 24 weeks of treatment.
measure: Adiponectin
timeFrame: Baseline and after 24 weeks of treatment.
measure: MMP-9
timeFrame: Baseline and after 24 weeks of treatment.
measure: OGTT parameters (insulin, intact proinsulin, glucose at time point 0, 60 and 120 minutes after 24 weeks
timeFrame: Baseline and after 24 weeks of treatment.
measure: HOMA-IR score
timeFrame: Baseline and after 24 weeks of treatment.
measure: HbA1c
timeFrame: Baseline and after 24 weeks of treatment.
measure: Weight
timeFrame: After 12 weeks of treatment compared to baseline and to 24 weeks of treatment.
measure: hsCRP
timeFrame: After 12 weeks of treatment compared to baseline and to 24 weeks of treatment.
measure: Adiponectin
timeFrame: After 12 weeks of treatment compared to baseline and to 24 weeks of treatment.
measure: Fasting intact Proinsulin
timeFrame: After 12 weeks of treatment compared to baseline and to 24 weeks of treatment.
measure: Glucose
timeFrame: After 12 weeks of treatment compared to baseline and to 24 weeks of treatment.
measure: HbA1c
timeFrame: After 12 weeks of treatment compared to baseline and to 24 weeks of treatment.
measure: Responder rate
timeFrame: After 24 weeks of treatment compared to baseline.
measure: Hypoglycemic events.
timeFrame: Baseline up to 24 weeks.
Other outcomes:
Locations:
city: Mainz
country: Germany
facility: ikfe GmbH
state: Rheinland-Pfalz
Study officials:
affiliation: Ikfe GmbH
name: Andreas Pfützner, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.