Effect of Linagliptin on Vascular Inflammation in Patients With Type 2 Diabetes Mellitus (Lina-Plaque)

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

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.

Study Overview

• Status: Terminated
• Conditions: Diabetes Mellitus Type 2 (T2DM); Vascular Inflammation; Plaque Morphology
• Intervention / Treatment: Drug: Placebo; Drug: Linagliptin

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 Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Aachen, Germany, 52074
    • Department of Internal Medicine I, University Hospital
• Netherlands
  • Maastricht, Netherlands, 6229
    • Cardiovascular Research Institute Maastricht (CARIM)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: RWTH Aachen University
• Investigators: Principal Investigator: Nikolaus Marx, Univ.-Prof., Department of Internal Medicine I, RWTH Aachen University Hospital

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: February 28, 2014
• First Submitted That Met QC Criteria: March 3, 2014
• First Posted (Estimate): March 4, 2014

Study Record Updates

• Last Update Posted (Actual): April 12, 2017
• Last Update Submitted That Met QC Criteria: April 10, 2017
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: MRI,; T2DM,; vascular inflammation,; 18-FDG-PET,; plaque morphology,; DPP-4 Inhibition
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Inflammation; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Linagliptin
• Other Study ID Numbers: 12-027 (CaenUH); 111/13 (Other Identifier: Ethic Commitee); 2012-003859-12 (EudraCT Number)