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

Phase 3

Terminated

• Conditions: Diabetes Mellitus Type 2 (T2DM); Vascular Inflammation; Plaque Morphology
• Interventions: Drug: Placebo; Drug: Linagliptin

• Registration Number: NCT02077309
• Lead Sponsor: RWTH Aachen University

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.

Study Timeline

• Study First Submitted: 2014-02-28
• Study First Submitted QC: 2014-03-03
• Study First Posted: 2014-03-04
• Study Start: 2014-08
• Primary Completion: 2015-09
• Study Completion: 2015-11
• Status Verified: 2015-12
• Last Update Submitted: 2017-04-10
• Last Update Posted: 2017-04-12

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 4

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Patients will take placebo tablets once daily for a period of 6 months.
Linagliptin	Linagliptin	Patients will receive 5 mg linagliptin once daily for a period of 6 months.

Primary Outcome Measures

Name	Time	Method
Effect of linagliptin on vascular inflammation of the carotic artery	up to 6 months	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.

Secondary Outcome Measures

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

Trial Locations

Locations (2)

Department of Internal Medicine I, University Hospital; 🇩🇪 Aachen, Germany

Cardiovascular Research Institute Maastricht (CARIM); 🇳🇱 Maastricht, Netherlands