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

NCT ID: NCT02077309

Last Updated: 2017-04-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-08-31
• Study Completion Date: 2015-11-30

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.

Conditions

Diabetes Mellitus Type 2 (T2DM); Vascular Inflammation; Plaque Morphology

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Linagliptin

Patients will receive 5 mg linagliptin once daily for a period of 6 months.

Group Type: ACTIVE_COMPARATOR

Linagliptin

Intervention Type: DRUG

Placebo

Patients will take placebo tablets once daily for a period of 6 months.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

Linagliptin

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Other Intervention Names

Trade name Trajenta® by Boehringer Ingelheim (BI) Pharma GmbH & Co KG, Biberach, Germany; Produced by Boehringer Ingelheim (BI) Pharma GmbH & Co KG, Biberach, Germany

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

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

RWTH Aachen University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nikolaus Marx, Univ.-Prof.

Role: PRINCIPAL_INVESTIGATOR

Department of Internal Medicine I, RWTH Aachen University Hospital

Locations

Department of Internal Medicine I, University Hospital

Aachen, , Germany

Cardiovascular Research Institute Maastricht (CARIM)

Maastricht, , Netherlands

Countries

Germany; Netherlands

Other Identifiers

111/13

Identifier Type: OTHER

Identifier Source: secondary_id

2012-003859-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

12-027

Identifier Type: -

Identifier Source: org_study_id