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

Sponsor

RWTH Aachen University (Other)

Overall Status

Terminated

CT.gov ID

NCT02077309

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus Type 2 (T2DM) Vascular Inflammation Plaque Morphology	Drug: Linagliptin Drug: Placebo	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

4 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Aug 1, 2014

Actual Primary Completion Date :

Sep 1, 2015

Actual Study Completion Date :

Nov 1, 2015

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Internal Medicine I, University Hospital	Aachen		Germany	52074
2	Cardiovascular Research Institute Maastricht (CARIM)	Maastricht		Netherlands	6229