Effect of Linagliptin on Vascular Inflammation in Patients With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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Examination of the effect of Linagliptin versus placebo for 6 months on vascular inflammation of the carotic artery and on abdominal adipose tissue inflammation in patients with diabetes mellitus type 2. The effect will be assessed by FDG-PET scan. Furthermore the effect of Linagliptin on the vessel wall volume of the carotid artery will be assessed by MRI scan and biomarkers of vascular inflammation will be analyzed in blood samples.

Detailed Description
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As part of the screening a PET-CT scan is executed to examine baseline vascular inflammation of the carotid artery and to evaluate abdominal adipose tissues inflammation. Patients who are eligible to participate in the study according to the in- and exclusion criteria will be randomised in one of the two study arms. According to the randomisation the patients will receive 5 mg Linagliptin or placebo per day for a period of 6 months. To evaluate the effect of Linagliptin versus placebo the vessel wall volume of the artery will be assessed by MRI scan and the vascular inflammation of the carotid artery by FDG-PET, furthermore the vascular inflammation will be analyzed by biomarkers in blood samples and the abdominal adipose tissue inflammation will investigated by subcutaneous adipose tissue biopsies.

Official Title
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Linagliptin as a Modulator of Vascular Inflammation in Patients With Type 2 Diabetes Mellitus

Conditions
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Diabetes Mellitus Type 2 (T2DM), Vascular Inflammation, Plaque Morphology

Intervention / Treatment
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* Drug: Linagliptin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diabetes mellitus Type 2 HbA1c > 7% Age > 50 years Coronary artery disease or carotid artery disease 18F-FDG uptake of the carotid arterial wall to background (blood) ratio > 1.8 Written informed consent prior to study participation Stable anti-diabetic and cholesterol lowering medication for the last 3 month Stable anti-diabetic medication for the last 6 weeks which should include a maximal tolerated dose of metformin (unless contraindication or intolerance to metformin does exist); Indication to increase anti-diabetic medication as judged by the investigator Exclusion Criteria: Diabetes mellitus type 1 Use of DPP-4 Inhibitor, GLP-1 agonists, Thiazolindinedione Kidney disease CKD 4 and more (GFR < 30 ml/min/1.73) Liver disease (ALT or AST > 3 times the upper limit of norm) or known liver cirrhosis Any reason for not being able to sustain the imaging studies Pacemaker/ICD/metallic clips in close relation to vessels in the brain Uncontrolled thyroid disease Active malignant disease Chronic inflammatory disease Chronic use of NSAR or cortison HbA1c > 8.5% Recent (<3 months) clinically significant coronary or cerebral vascular event Pregnant females as determined by positive [serum or urine] HCG test at Screening or prior to dosing Lactating females The subject has a history of any other illness, which, in the opinion of the Investigator, might pose an unacceptable risk by administering study medication The subject received an investigational drug within 30 days prior to inclusion into this study The subject has any current or past medical condition and/or required medication to treat a condition that could affect the evaluation of the study The subject is unwilling or unable to follow the procedures outlined in the protocol The subject is mentally or legally incapacitated

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Linagliptin<br>Patients will receive 5 mg linagliptin once daily for a period of 6 months. | Drug: Linagliptin<br> <br> * Other names: Trade name Trajenta® by Boehringer Ingelheim (BI) Pharma GmbH & Co KG, Biberach, Germany;|
| Placebo Comparator: Placebo<br>Patients will take placebo tablets once daily for a period of 6 months. | Drug: Placebo<br> <br> * Other names: Produced by Boehringer Ingelheim (BI) Pharma GmbH & Co KG, Biberach, Germany;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of linagliptin on vascular inflammation of the carotic artery | Examination of the effect of 5 mg linagliptin qd versus placebo on vascular inflammation of the carotic artery by FDG-PET in patients with diabetes mellitus within 6 months. | up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of linagliptin on vessel wall volume of the carotid artery | Examination of the effect of 5mg linagliptin qd versus placebo on vessel wall volume of the carotid artery by MRI scan. | baseline and 6 months | 
| Effect of linagliptin on abdominal adipose tissue inflammation | Evaluation of the effect of 5mg linagliptin qd versus placebo on abdominal adipose tissue inflammation by FDG-PET in addition to adipose tissue biopsies. | baseline and 6 months | 
| Effect of linagliptin on biomarkers of vascular inflammation | Blood analysis to examine the effect of linagliptin on biomarkers of vascular inflammation. | baseline and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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T2DM,, vascular inflammation,, 18-FDG-PET,, plaque morphology,, MRI,, DPP-4 Inhibition