Clinical trial NCT02077309: Effect of Linagliptin on Vascular Inflammation in Patients With Type 2 Diabetes Mellitus
Official title: Linagliptin as a Modulator of Vascular Inflammation in Patients With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Diabetes Mellitus Type 2 (T2DM)
Vascular Inflammation
Plaque Morphology
Keywords: T2DM,
vascular inflammation,
18-FDG-PET,
plaque morphology,
MRI,
DPP-4 Inhibition
Lead sponsor: RWTH Aachen University
Sponsor class: OTHER
First posted: 2014-03-04
Enrollment: 4
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Diabetes mellitus Type 2
2. HbA1c \> 7%
3. Age \> 50 years
4. Coronary artery disease or carotid artery disease
5. 18F-FDG uptake of the carotid arterial wall to background (blood) ratio \> 1.8
6. Written informed consent prior to study participation
7. Stable anti-diabetic and cholesterol lowering medication for the last 3 month
8. 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);
9. Indication to increase anti-diabetic medication as judged by the investigator

Exclusion Criteria:

1. Diabetes mellitus type 1
2. Use of DPP-4 Inhibitor, GLP-1 agonists, Thiazolindinedione
3. Kidney disease CKD 4 and more (GFR \< 30 ml/min/1.73)
4. Liver disease (ALT or AST \> 3 times the upper limit of norm) or known liver cirrhosis
5. Any reason for not being able to sustain the imaging studies
6. Pacemaker/ICD/metallic clips in close relation to vessels in the brain
7. Uncontrolled thyroid disease
8. Active malignant disease
9. Chronic inflammatory disease
10. Chronic use of NSAR or cortison
11. HbA1c \> 8.5%
12. Recent (\<3 months) clinically significant coronary or cerebral vascular event
13. Pregnant females as determined by positive \[serum or urine\] HCG test at Screening or prior to dosing
14. Lactating females
15. 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
16. The subject received an investigational drug within 30 days prior to inclusion into this study
17. 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
18. The subject is unwilling or unable to follow the procedures outlined in the protocol
19. The subject is mentally or legally incapacitated

Primary outcomes:
measure: Effect of linagliptin on vascular inflammation of the carotic artery
timeFrame: up to 6 months
Secondary outcomes:
measure: Effect of linagliptin on vessel wall volume of the carotid artery
timeFrame: baseline and 6 months
measure: Effect of linagliptin on abdominal adipose tissue inflammation
timeFrame: baseline and 6 months
measure: Effect of linagliptin on biomarkers of vascular inflammation
timeFrame: baseline and 6 months
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: Department of Internal Medicine I, University Hospital
city: Maastricht
country: Netherlands
facility: Cardiovascular Research Institute Maastricht (CARIM)
Study officials:
affiliation: Department of Internal Medicine I, RWTH Aachen University Hospital
name: Nikolaus Marx, Univ.-Prof.
role: PRINCIPAL_INVESTIGATOR
References: