Trial Outcomes & Findings for Effects of Linagliptin on Endothelial Function (NCT NCT02350478)
NCT ID: NCT02350478
Last Updated: 2020-05-15
Results Overview
Endothelium-dependent FMD following reactive hyperaemia was examined in the brachial artery according to the guidelines described by Coretti et al (J Am Coll Cardiol. 2002;39(2):257-65). FMD-diameter is calculated as the average of the three diameter measurements following reactive hyperaemia. FMD was calculated as the percent change in diameter compared to baseline. Flow-mediated dilation is reported such as "percentage of change in diameter (%)".
COMPLETED
PHASE4
49 participants
12 weeks
2020-05-15
Participant Flow
Participant milestones
| Measure |
Linagliptin
The subjects will receive Linagliptin 5mg (licensed dose for treatment of type 2 diabetes) .
Linagliptin: The subject will receive Linagliptin 5mg orally once daily for 12 weeks.
|
Placebo
The subjects will receive placebo.
Placebo: The subject will receive placebo orally once daily for 12 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
25
|
24
|
|
Overall Study
COMPLETED
|
20
|
23
|
|
Overall Study
NOT COMPLETED
|
5
|
1
|
Reasons for withdrawal
| Measure |
Linagliptin
The subjects will receive Linagliptin 5mg (licensed dose for treatment of type 2 diabetes) .
Linagliptin: The subject will receive Linagliptin 5mg orally once daily for 12 weeks.
|
Placebo
The subjects will receive placebo.
Placebo: The subject will receive placebo orally once daily for 12 weeks.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
5
|
1
|
Baseline Characteristics
Effects of Linagliptin on Endothelial Function
Baseline characteristics by cohort
| Measure |
Linagliptin
n=20 Participants
The subjects will receive Linagliptin 5mg (licensed dose for treatment of type 2 diabetes) .
Linagliptin: The subject will receive Linagliptin 5mg orally once daily for 12 weeks.
|
Placebo
n=23 Participants
The subjects will receive placebo.
Placebo: The subject will receive placebo orally once daily for 12 weeks.
|
Total
n=43 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
63.3 years
STANDARD_DEVIATION 7.8 • n=99 Participants
|
63.3 years
STANDARD_DEVIATION 8.7 • n=107 Participants
|
63.3 years
STANDARD_DEVIATION 8.2 • n=206 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
9 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=99 Participants
|
19 Participants
n=107 Participants
|
34 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
20 Participants
n=99 Participants
|
23 Participants
n=107 Participants
|
43 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Region of Enrollment
Austria
|
20 participants
n=99 Participants
|
23 participants
n=107 Participants
|
43 participants
n=206 Participants
|
|
Blood pressure systolic (mmHg)
|
134 mmHg
STANDARD_DEVIATION 17 • n=99 Participants
|
128 mmHg
STANDARD_DEVIATION 18 • n=107 Participants
|
131 mmHg
STANDARD_DEVIATION 18 • n=206 Participants
|
|
Blood pressure diastolic (mmHg)
|
79 mmHg
STANDARD_DEVIATION 14 • n=99 Participants
|
78 mmHg
STANDARD_DEVIATION 10 • n=107 Participants
|
79 mmHg
STANDARD_DEVIATION 12 • n=206 Participants
|
|
Low density lipoprotein (mg/dl)
|
66 mg/dl
STANDARD_DEVIATION 31 • n=99 Participants
|
76 mg/dl
STANDARD_DEVIATION 43 • n=107 Participants
|
71 mg/dl
STANDARD_DEVIATION 37 • n=206 Participants
|
|
Triglycerides (mg/dl)
|
145 mg/dl
n=99 Participants
|
122 mg/dl
n=107 Participants
|
128 mg/dl
n=206 Participants
|
|
HbA1c (mmol/mol)
|
50.5 mmol/mol
n=99 Participants
|
51 mmol/mol
n=107 Participants
|
51 mmol/mol
n=206 Participants
|
|
Fasting blood glucose
|
136 mg/dl
STANDARD_DEVIATION 41 • n=99 Participants
|
123 mg/dl
STANDARD_DEVIATION 26 • n=107 Participants
|
135 mg/dl
STANDARD_DEVIATION 35 • n=206 Participants
|
|
Aspartate-Aminotransferase (U/L)
|
33.5 U/l
STANDARD_DEVIATION 14 • n=99 Participants
|
27.6 U/l
STANDARD_DEVIATION 8.3 • n=107 Participants
|
30.4 U/l
STANDARD_DEVIATION 11.6 • n=206 Participants
|
|
Alanine-Aminotransferase (U/L)
|
40.4 U/l
STANDARD_DEVIATION 25 • n=99 Participants
|
29 U/l
STANDARD_DEVIATION 12.7 • n=107 Participants
|
34.4 U/l
STANDARD_DEVIATION 20.1 • n=206 Participants
|
|
Creatinine (mg/dL)
|
1.0 mg/dl
STANDARD_DEVIATION 0.3 • n=99 Participants
|
1.0 mg/dl
STANDARD_DEVIATION 0.2 • n=107 Participants
|
1.0 mg/dl
STANDARD_DEVIATION 0.3 • n=206 Participants
|
|
estimated glomerular filtration rate (ml/min)
|
76.7 ml/min
STANDARD_DEVIATION 16.1 • n=99 Participants
|
80.8 ml/min
STANDARD_DEVIATION 18.0 • n=107 Participants
|
78.9 ml/min
STANDARD_DEVIATION 17.0 • n=206 Participants
|
|
c-reactive protein (mg/L)
|
3.8 mg/dl
STANDARD_DEVIATION 4.2 • n=99 Participants
|
7.6 mg/dl
STANDARD_DEVIATION 20.4 • n=107 Participants
|
5.8 mg/dl
STANDARD_DEVIATION 15.2 • n=206 Participants
|
|
Urine albumine´(mg/L)
|
51.8 mg/l
STANDARD_DEVIATION 68.1 • n=99 Participants
|
30.3 mg/l
STANDARD_DEVIATION 43.4 • n=107 Participants
|
40.8 mg/l
STANDARD_DEVIATION 57.1 • n=206 Participants
|
|
n-terminal-proBNP (pg/ml)
|
419 pg/ml
STANDARD_DEVIATION 528 • n=99 Participants
|
228 pg/ml
STANDARD_DEVIATION 452 • n=107 Participants
|
317 pg/ml
STANDARD_DEVIATION 492 • n=206 Participants
|
PRIMARY outcome
Timeframe: 12 weeksEndothelium-dependent FMD following reactive hyperaemia was examined in the brachial artery according to the guidelines described by Coretti et al (J Am Coll Cardiol. 2002;39(2):257-65). FMD-diameter is calculated as the average of the three diameter measurements following reactive hyperaemia. FMD was calculated as the percent change in diameter compared to baseline. Flow-mediated dilation is reported such as "percentage of change in diameter (%)".
Outcome measures
| Measure |
Linagliptin
n=20 Participants
The subjects will receive Linagliptin 5mg (licensed dose for treatment of type 2 diabetes) .
Linagliptin: The subject will receive Linagliptin 5mg orally once daily for 12 weeks.
|
Placebo
n=23 Participants
The subjects will receive placebo.
Placebo: The subject will receive placebo orally once daily for 12 weeks.
|
|---|---|---|
|
Changes in Endothelial Function (FMD - Flow Mediated Dilatation) From Baseline to 12 Weeks
|
0.4 percentage of change in diameter (%)
Standard Deviation 4.8
|
-0.5 percentage of change in diameter (%)
Standard Deviation 3.0
|
SECONDARY outcome
Timeframe: 12 weeksArginine, ornithine and citrulline will be measured in serum samples with a conventional usual amino acid analysis technique, involving separation of amino acids by ion exchange chromatography followed by postcolumn continuous reaction with ninhydrin. Global arginine bioavailability ratio (GABR) will be calculated by L-arginine divided by the sum of (L-ornithine plus L-citrulline). The arginine to ornithine ratio will be calculated by dividing L-arginine by L-ornithine levels.
Outcome measures
| Measure |
Linagliptin
n=20 Participants
The subjects will receive Linagliptin 5mg (licensed dose for treatment of type 2 diabetes) .
Linagliptin: The subject will receive Linagliptin 5mg orally once daily for 12 weeks.
|
Placebo
n=23 Participants
The subjects will receive placebo.
Placebo: The subject will receive placebo orally once daily for 12 weeks.
|
|---|---|---|
|
Changes in Global Arginine Bioavailability Ratio (Ratio of Arginine to [Ornithine + Citrulline]) and Arginine to Ornithine Ratio From Baseline to 12 Weeks
Global Arginine Bioavailabilty Ratio (%)
|
-0.11 Ratio
Standard Deviation 0.35
|
-0.06 Ratio
Standard Deviation 0.39
|
|
Changes in Global Arginine Bioavailability Ratio (Ratio of Arginine to [Ornithine + Citrulline]) and Arginine to Ornithine Ratio From Baseline to 12 Weeks
Arginine to ornithine ratio (%)
|
-0.13 Ratio
Standard Deviation 0.45
|
-0.05 Ratio
Standard Deviation 0.53
|
SECONDARY outcome
Timeframe: 12 weeksSoluble cell adhesion molecules-1 (sICAM-1) of endothelial function from baseline to 12 weeks
Outcome measures
| Measure |
Linagliptin
n=20 Participants
The subjects will receive Linagliptin 5mg (licensed dose for treatment of type 2 diabetes) .
Linagliptin: The subject will receive Linagliptin 5mg orally once daily for 12 weeks.
|
Placebo
n=23 Participants
The subjects will receive placebo.
Placebo: The subject will receive placebo orally once daily for 12 weeks.
|
|---|---|---|
|
Changes in Biochemical Markers (sICAM-1)
|
-15 ng/ml
Interval -272.0 to 103.0
|
-21 ng/ml
Interval -134.0 to 310.0
|
SECONDARY outcome
Timeframe: 12 weeksThe Area under the curve was calculated for glucose, insulin and for the free fatty acids based on the trapezoidal rule with baseline value as the mean of the values at time points -5 and 0 minutes. The Meal Tolerance Test (MTT) was performed after an overnight fast (apart from water). A pre-meal blood sample will be taken (-5mins) and then all subjects will be asked to drink Fortimel compact (10 kcal/kg) over a period of 2-4 mins (time 0 mins). During the mixed meal test further blood samples will be taken at 15, 30, 60, and 120 minutes. All samples will be used for the determination of glucose, insulin and free fatty acids. The blood at each time point will be placed into a fluoride oxalate tube (1ml) for plasma glucose and into a serum tube for insulin and free fatty acids.
Outcome measures
| Measure |
Linagliptin
n=20 Participants
The subjects will receive Linagliptin 5mg (licensed dose for treatment of type 2 diabetes) .
Linagliptin: The subject will receive Linagliptin 5mg orally once daily for 12 weeks.
|
Placebo
n=23 Participants
The subjects will receive placebo.
Placebo: The subject will receive placebo orally once daily for 12 weeks.
|
|---|---|---|
|
Changes in the Area Under Curve (AUC) of Glucose, Insulin and C-peptide During the Meal Tolerance Test From Baseline to 12 Weeks
Glucose AUC
|
-1135 mg*min/dl
Standard Deviation 2619
|
481 mg*min/dl
Standard Deviation 3185
|
|
Changes in the Area Under Curve (AUC) of Glucose, Insulin and C-peptide During the Meal Tolerance Test From Baseline to 12 Weeks
C-peptide AUC
|
-3 mg*min/dl
Standard Deviation 161
|
-34 mg*min/dl
Standard Deviation 211
|
|
Changes in the Area Under Curve (AUC) of Glucose, Insulin and C-peptide During the Meal Tolerance Test From Baseline to 12 Weeks
Insulin AUC
|
249 mg*min/dl
Standard Deviation 4766
|
40 mg*min/dl
Standard Deviation 6357
|
SECONDARY outcome
Timeframe: 12 weeksThe Area under the curve was calculated for glucose, insulin and for the free fatty acids based on the trapezoidal rule with baseline value as the mean of the values at time points -5 and 0 minutes. The MTT was performed after an overnight fast (apart from water). A pre-meal blood sample will be taken (-5mins) and then all subjects will be asked to drink Fortimel compact (10 kcal/kg) over a period of 2-4 mins (time 0 mins). During the mixed meal test further blood samples will be taken at 15, 30, 60, and 120 minutes. All samples will be used for the determination of glucose, insulin and free fatty acids. The blood at each time point will be placed into a fluoride oxalate tube (1ml) for plasma glucose and into a serum tube for insulin and free fatty acids.
Outcome measures
| Measure |
Linagliptin
n=20 Participants
The subjects will receive Linagliptin 5mg (licensed dose for treatment of type 2 diabetes) .
Linagliptin: The subject will receive Linagliptin 5mg orally once daily for 12 weeks.
|
Placebo
n=23 Participants
The subjects will receive placebo.
Placebo: The subject will receive placebo orally once daily for 12 weeks.
|
|---|---|---|
|
Changes in the Area Under Curve (AUC) of Free Fatty Acids During the Meal Tolerance Test From Baseline to 12 Weeks
|
2.0 µmol*min/l
Standard Deviation 28.4
|
-3.1 µmol*min/l
Standard Deviation 18.3
|
SECONDARY outcome
Timeframe: 12 weeksSoluble cell adhesion molecules-1 (svCAM-1) of endothelial function from baseline to 12 weeks
Outcome measures
| Measure |
Linagliptin
n=20 Participants
The subjects will receive Linagliptin 5mg (licensed dose for treatment of type 2 diabetes) .
Linagliptin: The subject will receive Linagliptin 5mg orally once daily for 12 weeks.
|
Placebo
n=23 Participants
The subjects will receive placebo.
Placebo: The subject will receive placebo orally once daily for 12 weeks.
|
|---|---|---|
|
Changes in Biochemical Markers (svCAM-1)
|
-34 ng/ml
Standard Deviation 84
|
5 ng/ml
Standard Deviation 130
|
Adverse Events
Linagliptin
Placebo
Serious adverse events
| Measure |
Linagliptin
n=20 participants at risk
The subjects will receive Linagliptin 5mg (licensed dose for treatment of type 2 diabetes) .
Linagliptin: The subject will receive Linagliptin 5mg orally once daily for 12 weeks.
|
Placebo
n=23 participants at risk
The subjects will receive placebo.
Placebo: The subject will receive placebo orally once daily for 12 weeks.
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
discus prolaps
|
5.0%
1/20 • Number of events 1 • Adverse events were collected for 16 weeks (12 weeks of intervention and 4 weeks of follow-up).
|
0.00%
0/23 • Adverse events were collected for 16 weeks (12 weeks of intervention and 4 weeks of follow-up).
|
|
Infections and infestations
Borreliosis
|
0.00%
0/20 • Adverse events were collected for 16 weeks (12 weeks of intervention and 4 weeks of follow-up).
|
4.3%
1/23 • Number of events 1 • Adverse events were collected for 16 weeks (12 weeks of intervention and 4 weeks of follow-up).
|
|
Nervous system disorders
Coordinating disorders
|
5.0%
1/20 • Number of events 1 • Adverse events were collected for 16 weeks (12 weeks of intervention and 4 weeks of follow-up).
|
0.00%
0/23 • Adverse events were collected for 16 weeks (12 weeks of intervention and 4 weeks of follow-up).
|
|
Gastrointestinal disorders
Abdominal pain
|
5.0%
1/20 • Number of events 1 • Adverse events were collected for 16 weeks (12 weeks of intervention and 4 weeks of follow-up).
|
0.00%
0/23 • Adverse events were collected for 16 weeks (12 weeks of intervention and 4 weeks of follow-up).
|
Other adverse events
| Measure |
Linagliptin
n=20 participants at risk
The subjects will receive Linagliptin 5mg (licensed dose for treatment of type 2 diabetes) .
Linagliptin: The subject will receive Linagliptin 5mg orally once daily for 12 weeks.
|
Placebo
n=23 participants at risk
The subjects will receive placebo.
Placebo: The subject will receive placebo orally once daily for 12 weeks.
|
|---|---|---|
|
Nervous system disorders
Dorsal pain
|
5.0%
1/20 • Number of events 1 • Adverse events were collected for 16 weeks (12 weeks of intervention and 4 weeks of follow-up).
|
0.00%
0/23 • Adverse events were collected for 16 weeks (12 weeks of intervention and 4 weeks of follow-up).
|
|
Gastrointestinal disorders
Toothache
|
5.0%
1/20 • Number of events 1 • Adverse events were collected for 16 weeks (12 weeks of intervention and 4 weeks of follow-up).
|
0.00%
0/23 • Adverse events were collected for 16 weeks (12 weeks of intervention and 4 weeks of follow-up).
|
|
Vascular disorders
Claudicatio intermittens
|
0.00%
0/20 • Adverse events were collected for 16 weeks (12 weeks of intervention and 4 weeks of follow-up).
|
4.3%
1/23 • Number of events 1 • Adverse events were collected for 16 weeks (12 weeks of intervention and 4 weeks of follow-up).
|
|
Cardiac disorders
Hypotension
|
0.00%
0/20 • Adverse events were collected for 16 weeks (12 weeks of intervention and 4 weeks of follow-up).
|
4.3%
1/23 • Number of events 1 • Adverse events were collected for 16 weeks (12 weeks of intervention and 4 weeks of follow-up).
|
|
General disorders
Nausea
|
5.0%
1/20 • Number of events 1 • Adverse events were collected for 16 weeks (12 weeks of intervention and 4 weeks of follow-up).
|
4.3%
1/23 • Number of events 1 • Adverse events were collected for 16 weeks (12 weeks of intervention and 4 weeks of follow-up).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place