Clinical trial NCT01703286: Trial to Assess the Influence of 4 Weeks' Treatment With Linagliptin as Compared to Glimepiride and Placebo on Endothelial Function in Patients With Type 2 Diabetes Using FMD (Flow-Mediated Vasodilation)
Official title: Randomized, Three Period Cross Over, Double Blind, Double Dummy Study in Type 2 Diabetic Patients to Assess the Endothelial Effects of Linagliptin, Glimepiride and Placebo Therapy for 28 Days ('ENDOTHELINA')
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
Collaborators: name: Eli Lilly and Company
First posted: 2012-10-10
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The general aim of the present study is to investigate the impact of 4 weeks treatment with linagliptin (5 mg) on endothelial function in patients with type 2 diabetes mellitus. In the current trial this effect of linagliptin treatment on endothelial function will be compared against both the sulfonylurea glimepiride and against placebo, which has not been tested in a trial before; as also is the case for other DPP-4 inhibitors.

Besides placebo, glimepiride was chosen as a comparator, as it is one compound of the second most used oral antidiabetic drug class.


Eligibility criteria: Inclusion criteria:

1. Type 2 diabetic male and female patients according to the following criteria:

   Based upon a complete medical history and clinical laboratory tests
2. Age \>= 18 and Age \<= 65 years
3. Body mass index \>= 25 \<= 35 kg/m2
4. HbA1c \<= 7.5%
5. Treatment with metformin (=1500 mg daily) for \<= 3 months
6. Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation.

   For female patients of childbearing potential:
7. Use of acceptable method of contraception (Pearl-Index \<1).

Exclusion criteria:

1. Treatment with any glucose-lowering drug except for metformin within prior 3 months.
2. Any finding of the medical examination (including blood pressure, pulse rate and electrocardiogram) deviating from normal and of clinical relevance.
3. Any evidence of a clinically relevant acute concomitant disease
4. History of cardiovascular disease (e.g. coronary artery disease history of acute myocard infarction or stroke, peripheral vascular disease).
5. History of major diabetic complications (e.g. nephropathy, retinopathy)
6. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, immunological or hormonal disorders (except: hypertension treated with angiotensin receptor blocker or angiotensin-converting-enzyme inhibitors, hyperlipidemia with statin therapy, thyroid hormone replacement therapy, all stable for at least three months prior to screening).
7. Surgery of the gastrointestinal tract (except appendectomy).
8. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders.
9. History of relevant orthostatic hypotension, fainting spells or blackouts.
10. Chronic or relevant acute infections.
11. History of relevant allergy/hypersensitivity (including allergy to drug or its excipients).
12. Intake of drugs with a long half-life (\> 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial.
13. Participation in another trial with an investigational drug within one month prior to administration or during the trial.
14. Smoker (\>= 1 cigarettes or \>= 1 cigars or \>= 1 pipes/day).
15. Alcohol abuse (more than 60 g/day).
16. Drug abuse.
17. Blood donation (more than 100 mL within four weeks prior to administration or during the trial).
18. Excessive physical activities (within one week prior to administration or during the trial).
19. Any laboratory value outside the reference range that is of clinical relevance.

Primary outcomes:
measure: Change From Baseline in Flow Mediated Vasodilation (FMD) Under Fasted Condition on Day 28
timeFrame: baseline and day 28 for each treatment arm
Secondary outcomes:
measure: Change From Baseline in Flow Mediated Vasodilation (FMD) 2 h Post Meal on Day 28
timeFrame: baseline and day 28 for each treatment arm
measure: Change From Baseline in 2 Hours Post Meal Endothelial Independent Vasodilation (EIDV) on Day 28
timeFrame: baseline and day 28 for each treatment arm
measure: Number of Patients With Adverse Events
timeFrame: up to 20 weeks
Other outcomes:
Locations:
city: Neuss
country: Germany
facility: 1218.105.001 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Jax T, Stirban A, Terjung A, Esmaeili H, Berk A, Thiemann S, Chilton R, von Eynatten M, Marx N. A randomised, active- and placebo-controlled, three-period crossover trial to investigate short-term effects of the dipeptidyl peptidase-4 inhibitor linagliptin on macro- and microvascular endothelial function in type 2 diabetes. Cardiovasc Diabetol. 2017 Jan 21;16(1):13. doi: 10.1186/s12933-016-0493-3.