type 2 diabetes mellitus MedDRA version: 17.1 Level: LLT Classification code 10045252 Term: Type II diabetes mellitus without mention of complication System Organ Class: 100000004861
Conditions
Interventions
Trade Name: Trajenta
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use
Sponsors
University Medical Center Groningen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Men and women, age 30 to 70 years, AND - Treatment naïve type 2 diabetes, as defined as the presence of one of the following (American Diabetes Association definition: - Fasting plasma glucose = 7.0 mmol/l, OR - Random plasma glucose = 11.1 mmol/l, OR - HbA1c =6,5% Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Current or previous use of glycemic control medications - Type 1 diabetes - Gestational diabetes mellitus - Other specific types of diabetes due to other causes - Uncontrolled hypertension, defined as systolic blood pressure >160 or a diastolic blood pressure >100 mmHg at screening visit - Severe dyslipidemia indicating primary dyslipidemia, defined as total cholesterol >8 mmol/l, tryglicerides >10 mmol/l of high density lipoprotein cholesterol <0.6 mmol/l - Current use of weight loss medication or previous weight loss surgery - History of severe gastrointestinal disease - Clinical contraindications to DPP4-inhibitors - Previous cardiovascular disease, defined as stable coronary artery disease or acute coronary syndrome, stroke or transient ischemic attack, peripheral artery disease - Symptomatic heart failure, New York Heart Association (NYHA) class II-IV - Women who are currently pregnant,planning to become pregnant,breastfeeding women, or women with child bearing potential not using appropriate contraceptive measures - Clinically significant liver disease or hepatic function greater than 3 times upper limit of normal - Known impaired renal function or eGFR <30 ml/min/1.73m2 - Patients who are mentally incompetent and cannot sign a Patient Informed Consent - Current active malignancy or in the previous 6 months - Documented HIV infection - Use of rifampicin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To assess whether linagliptin compared with placebo improves arterial stiffness in treatment naïve subjects with type 2 diabetes.;Secondary Objective: 2. To assess whether linagliptin compared with placebo improves blood pressure parameters, inflammatory and endothelial function markers, albuminuria, and vascular inflammation in treatment naïve subjects with type 2 diabetes. 3. To determine whether the off-target effects on arterial stiffness blood pressure parameters, inflammatory endothelial function markers and vascular inflammation are concordant with changes in glucose parameters, including HbA1c fasting plasma glucose, and beta-cell and insulin sensitivity indices.;Primary end point(s): Difference in mean Pulse Wave Velocity (PWV) after 26 weeks between the Linagliptin and placebo treated group.;Timepoint(s) of evaluation of this end point: 26 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Central Blood Pressure (CBP) and Augmentation Index (AI) obtained from pulse wave analysis, using Sphygmocor - Carotid-(left) radial arterial PWV, using Sphygmocor - Body Mass Index (BMI) and Waist-to-Hip ratio - 24-hours ambulatory blood pressure measurement (24-ABPM) - Urinary albumin/creatinine ratio (mean of 2 separate morning portions (ACR) - plasma markers of inflammation ( i.e. high-sensitivity C-reactive protein (hs-CRP); Interleukin-6; TNF-a, serum amyloid-A (SAA), myeloperoxidase (MPO)) - plasma markers of endothelial dysfunction (i.e. vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), soluble E-selectin, von Willebrand factor, tissue-type plasminogen activator), in vitro stimulated cytokine production by peripheral blood mononuclear cells (PBMC) - Glycemic indices: fasting glucose (FPG) and 2-hour post OGTT glucose (OGTT), HbA1c, fasting insulin, and derived indices (HOMA-ß (as a surrogate marker for ß –cell function) and HOMA-IR (insulin resistance), Matsuda index (insulin sensitivity) - Skin AGE deposition measured as skin autofluorescence using AGE reader and plasma levels of AGEs (N(e)-(carboxymethyl) lysine (CML), N(e)-(Carboxyethyl) lysine (CEL) - Intake of energy, Eating behaviour, and Physical activity - Target-to-background ratios (TBRs) (18)F-fluorodeoxyglucose positron emission tomography computed tomography coregistration (FDG PET-CT);Timepoint(s) of evaluation of this end point: 4, 26, and 30 weeks | — |
Countries
Netherlands
Contacts
Public ContactD.J. Mulder, project leader
University Medical Center Groningen (UMCG)
Outcome results
None listed