Trial Outcomes & Findings for The Effect of Linagliptin on Mitochondrial and Endothelial Function (NCT NCT01969084)
NCT ID: NCT01969084
Last Updated: 2016-11-18
Results Overview
Change in the time to phosphocreatine recovery between the baseline visit and post-treatment visit following the graded exercise test.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
45 participants
Primary outcome timeframe
Baseline and 12 weeks
Results posted on
2016-11-18
Participant Flow
45 subjects were enrolled and 41 were randomized to the study
Participant milestones
| Measure |
Linagliptin
Subjects given Linagliptin
Linagliptin
Microcirculation testing: The endothelial function of the micro-circulation was assessed by measuring the hyperemic response of the vessels in the superficial skin of the forearm after the iontophoresis of acetylcholine. The endothelium independent vasodilation will be assessed by the iontophoresis of sodium nitroprusside. Laser Doppler perfusion imaging will be used to measure relative changes in flow velocity.Visible and NIR Medical Hyperspectral Imaging (MHSI) data will be collected with a HyperMed OxyView MHSI System (HyperMed, Inc., Watertown, MA). MHSI images will be obtained from same forearm area where the iontophoresis of acetylcholine and sodium nitroprusside will be performed, before and after the iontophoresis test.
Macrocirculation testing: Use ultrasound to measure brachial artery flow mediated vasodilation (FMD, endothelium-dependent vasodilation) and nitroglycerin induced dilation (NID, endothelium-independent vasodila
|
Sugar Pill
Subjects given sugar pill/placebo
Placebo
Microcirculation testing: The endothelial function of the micro-circulation was assessed by measuring the hyperemic response of the vessels in the superficial skin of the forearm after the iontophoresis of acetylcholine. The endothelium independent vasodilation will be assessed by the iontophoresis of sodium nitroprusside. Laser Doppler perfusion imaging will be used to measure relative changes in flow velocity.Visible and NIR Medical Hyperspectral Imaging (MHSI) data will be collected with a HyperMed OxyView MHSI System (HyperMed, Inc., Watertown, MA). MHSI images will be obtained from same forearm area where the iontophoresis of acetylcholine and sodium nitroprusside will be performed, before and after the iontophoresis test.
Macrocirculation testing: Use ultrasound to measure brachial artery flow mediated vasodilation (FMD, endothelium-dependent vasodilation) and nitroglycerin induced dilation (NID, endothelium-independent vasod
|
|---|---|---|
|
Overall Study
STARTED
|
19
|
22
|
|
Overall Study
COMPLETED
|
19
|
21
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
Linagliptin
Subjects given Linagliptin
Linagliptin
Microcirculation testing: The endothelial function of the micro-circulation was assessed by measuring the hyperemic response of the vessels in the superficial skin of the forearm after the iontophoresis of acetylcholine. The endothelium independent vasodilation will be assessed by the iontophoresis of sodium nitroprusside. Laser Doppler perfusion imaging will be used to measure relative changes in flow velocity.Visible and NIR Medical Hyperspectral Imaging (MHSI) data will be collected with a HyperMed OxyView MHSI System (HyperMed, Inc., Watertown, MA). MHSI images will be obtained from same forearm area where the iontophoresis of acetylcholine and sodium nitroprusside will be performed, before and after the iontophoresis test.
Macrocirculation testing: Use ultrasound to measure brachial artery flow mediated vasodilation (FMD, endothelium-dependent vasodilation) and nitroglycerin induced dilation (NID, endothelium-independent vasodila
|
Sugar Pill
Subjects given sugar pill/placebo
Placebo
Microcirculation testing: The endothelial function of the micro-circulation was assessed by measuring the hyperemic response of the vessels in the superficial skin of the forearm after the iontophoresis of acetylcholine. The endothelium independent vasodilation will be assessed by the iontophoresis of sodium nitroprusside. Laser Doppler perfusion imaging will be used to measure relative changes in flow velocity.Visible and NIR Medical Hyperspectral Imaging (MHSI) data will be collected with a HyperMed OxyView MHSI System (HyperMed, Inc., Watertown, MA). MHSI images will be obtained from same forearm area where the iontophoresis of acetylcholine and sodium nitroprusside will be performed, before and after the iontophoresis test.
Macrocirculation testing: Use ultrasound to measure brachial artery flow mediated vasodilation (FMD, endothelium-dependent vasodilation) and nitroglycerin induced dilation (NID, endothelium-independent vasod
|
|---|---|---|
|
Overall Study
Adverse Event
|
0
|
1
|
Baseline Characteristics
The Effect of Linagliptin on Mitochondrial and Endothelial Function
Baseline characteristics by cohort
| Measure |
Linagliptin
n=19 Participants
Subjects given Linagliptin
Linagliptin
Microcirculation testing: The endothelial function of the micro-circulation was assessed by measuring the hyperemic response of the vessels in the superficial skin of the forearm after the iontophoresis of acetylcholine. The endothelium independent vasodilation will be assessed by the iontophoresis of sodium nitroprusside. Laser Doppler perfusion imaging will be used to measure relative changes in flow velocity.Visible and NIR Medical Hyperspectral Imaging (MHSI) data will be collected with a HyperMed OxyView MHSI System (HyperMed, Inc., Watertown, MA). MHSI images will be obtained from same forearm area where the iontophoresis of acetylcholine and sodium nitroprusside will be performed, before and after the iontophoresis test.
Macrocirculation testing: Use ultrasound to measure brachial artery flow mediated vasodilation (FMD, endothelium-dependent vasodilation) and nitroglycerin induced dilation (NID, endothelium-independent vasodila
|
Sugar Pill
n=22 Participants
Subjects given sugar pill/placebo
Placebo
Microcirculation testing: The endothelial function of the micro-circulation was assessed by measuring the hyperemic response of the vessels in the superficial skin of the forearm after the iontophoresis of acetylcholine. The endothelium independent vasodilation will be assessed by the iontophoresis of sodium nitroprusside. Laser Doppler perfusion imaging will be used to measure relative changes in flow velocity.Visible and NIR Medical Hyperspectral Imaging (MHSI) data will be collected with a HyperMed OxyView MHSI System (HyperMed, Inc., Watertown, MA). MHSI images will be obtained from same forearm area where the iontophoresis of acetylcholine and sodium nitroprusside will be performed, before and after the iontophoresis test.
Macrocirculation testing: Use ultrasound to measure brachial artery flow mediated vasodilation (FMD, endothelium-dependent vasodilation) and nitroglycerin induced dilation (NID, endothelium-independent vasod
|
Total
n=41 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
14 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
5 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Age, Continuous
|
60.79 years
STANDARD_DEVIATION 5.75 • n=5 Participants
|
56.76 years
STANDARD_DEVIATION 6.79 • n=7 Participants
|
58.67 years
STANDARD_DEVIATION 6.56 • n=5 Participants
|
|
Gender
Female
|
7 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Gender
Male
|
12 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
19 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
41 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and 12 weeksChange in the time to phosphocreatine recovery between the baseline visit and post-treatment visit following the graded exercise test.
Outcome measures
| Measure |
Linagliptin
n=19 Participants
Subjects given Linagliptin
Linagliptin
MRI Scans: Phosphorus-31 MRI data was obtained during an exercise protocol. Muscle oxygenation will be measured using the blood oxygenation level-dependent magnetic resonance imaging (BOLD MRI) technique after induced hyperemia.
|
Sugar Pill
n=21 Participants
Subjects given sugar pill/placebo
Placebo
MRI Scans: Phosphorus-31 MRI data was obtained during an exercise protocol. Muscle oxygenation will be measured using the blood oxygenation level-dependent magnetic resonance imaging (BOLD MRI) technique after induced hyperemia.
|
|---|---|---|
|
Phosphocreatine (PCR) Recovery Time After Exhaustive or up to 6 Minutes of Leg Exercise.
|
0.0 seconds
Interval -23.3 to 15.3
|
1.01 seconds
Interval -36.8 to 14.0
|
SECONDARY outcome
Timeframe: Baseline and 12 weeksChange in muscle oxygenation after ischemia inducing occlusion for 4 minutes.
Outcome measures
| Measure |
Linagliptin
n=19 Participants
Subjects given Linagliptin
Linagliptin
MRI Scans: Phosphorus-31 MRI data was obtained during an exercise protocol. Muscle oxygenation will be measured using the blood oxygenation level-dependent magnetic resonance imaging (BOLD MRI) technique after induced hyperemia.
|
Sugar Pill
n=21 Participants
Subjects given sugar pill/placebo
Placebo
MRI Scans: Phosphorus-31 MRI data was obtained during an exercise protocol. Muscle oxygenation will be measured using the blood oxygenation level-dependent magnetic resonance imaging (BOLD MRI) technique after induced hyperemia.
|
|---|---|---|
|
Change in Muscle Oxygenation Recovery Time
Medial gastrocnemius
|
2.6 seconds
Interval -6.2 to 13.9
|
7.1 seconds
Interval -7.1 to 10.1
|
|
Change in Muscle Oxygenation Recovery Time
Lateral gastrocnemius
|
2.8 seconds
Interval -6.6 to 11.3
|
2.2 seconds
Interval -9.1 to 8.1
|
|
Change in Muscle Oxygenation Recovery Time
Soleus
|
0.3 seconds
Interval -3.6 to 3.9
|
-1.6 seconds
Interval -3.9 to 2.2
|
|
Change in Muscle Oxygenation Recovery Time
Tibialis anterior
|
2.9 seconds
Interval 1.2 to 27.1
|
2.40 seconds
Interval -6.6 to 8.6
|
|
Change in Muscle Oxygenation Recovery Time
Peroneus Longus
|
0.4 seconds
Interval -4.0 to 7.1
|
-0.12 seconds
Interval -2.0 to 2.6
|
SECONDARY outcome
Timeframe: Baseline and 12 weeksChange in markers of macro- and microvascular function from the baseline visit to the post-treatment visit between the two groups.
Outcome measures
| Measure |
Linagliptin
n=19 Participants
Subjects given Linagliptin
Linagliptin
MRI Scans: Phosphorus-31 MRI data was obtained during an exercise protocol. Muscle oxygenation will be measured using the blood oxygenation level-dependent magnetic resonance imaging (BOLD MRI) technique after induced hyperemia.
|
Sugar Pill
n=21 Participants
Subjects given sugar pill/placebo
Placebo
MRI Scans: Phosphorus-31 MRI data was obtained during an exercise protocol. Muscle oxygenation will be measured using the blood oxygenation level-dependent magnetic resonance imaging (BOLD MRI) technique after induced hyperemia.
|
|---|---|---|
|
Changes in Vascular Reactivity in the Micro- and Macro-circulation.
ACh LDPI
|
14.2 percent change
Interval -9.5 to 25.4
|
-6.1 percent change
Interval -15.3 to 22.6
|
|
Changes in Vascular Reactivity in the Micro- and Macro-circulation.
ACh axon reflex
|
48.5 percent change
Interval -47.8 to 125.7
|
-7.4 percent change
Interval -259.2 to 153.2
|
|
Changes in Vascular Reactivity in the Micro- and Macro-circulation.
Flow mediated dilation
|
0.67 percent change
Interval -0.58 to 1.58
|
0.36 percent change
Interval -0.38 to 1.21
|
|
Changes in Vascular Reactivity in the Micro- and Macro-circulation.
Nitroglycerin mediated dilation
|
0.27 percent change
Interval -0.78 to 1.62
|
0.11 percent change
Interval -0.91 to 1.21
|
SECONDARY outcome
Timeframe: Baseline and 12 weeksOutcome measures
| Measure |
Linagliptin
n=19 Participants
Subjects given Linagliptin
Linagliptin
MRI Scans: Phosphorus-31 MRI data was obtained during an exercise protocol. Muscle oxygenation will be measured using the blood oxygenation level-dependent magnetic resonance imaging (BOLD MRI) technique after induced hyperemia.
|
Sugar Pill
n=21 Participants
Subjects given sugar pill/placebo
Placebo
MRI Scans: Phosphorus-31 MRI data was obtained during an exercise protocol. Muscle oxygenation will be measured using the blood oxygenation level-dependent magnetic resonance imaging (BOLD MRI) technique after induced hyperemia.
|
|---|---|---|
|
Changes in SDF1-α and Substance P
SDF-1
|
3 pg/ml
Interval -100.0 to 28.0
|
11.1 pg/ml
Interval -1.2 to 53.0
|
|
Changes in SDF1-α and Substance P
Substance P
|
77.4 pg/ml
Interval -69.7 to 348.0
|
42.2 pg/ml
Interval -349.0 to 138.8
|
SECONDARY outcome
Timeframe: Baseline and 12 weeksThe measurements of the various EPC phenotypes were performed at the Beth Israel Deaconess Flow Cytometry Core Facility. Immunofluorescent cell staining was performed on peripheral blood with the use of the fluorescent conjugated antibodies. 1.000.000 events per sample were acquired using a FACS LSR II analyzer (Becton Dickinson, Franklin Lakes, NJ, USA) and the results were analyzed using the Beckman Coulter Kaluza analysis software (Beckman Coulter Inc., Brea, CA, USA).
Outcome measures
| Measure |
Linagliptin
n=19 Participants
Subjects given Linagliptin
Linagliptin
MRI Scans: Phosphorus-31 MRI data was obtained during an exercise protocol. Muscle oxygenation will be measured using the blood oxygenation level-dependent magnetic resonance imaging (BOLD MRI) technique after induced hyperemia.
|
Sugar Pill
n=21 Participants
Subjects given sugar pill/placebo
Placebo
MRI Scans: Phosphorus-31 MRI data was obtained during an exercise protocol. Muscle oxygenation will be measured using the blood oxygenation level-dependent magnetic resonance imaging (BOLD MRI) technique after induced hyperemia.
|
|---|---|---|
|
Changes in Circulating Endothelial Progenitor Cell Phenotypes
CD133-KDR
|
5 Events per million
Interval -20.0 to 111.0
|
1 Events per million
Interval -45.0 to 40.0
|
|
Changes in Circulating Endothelial Progenitor Cell Phenotypes
KDR-CD34
|
1 Events per million
Interval -26.0 to 74.0
|
1 Events per million
Interval -15.0 to 49.0
|
|
Changes in Circulating Endothelial Progenitor Cell Phenotypes
CD133-CD34-KDR
|
4 Events per million
Interval -4.0 to 102.0
|
-3 Events per million
Interval -15.0 to 5.0
|
Adverse Events
Linagliptin
Serious events: 1 serious events
Other events: 2 other events
Deaths: 0 deaths
Sugar Pill
Serious events: 3 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Linagliptin
n=19 participants at risk
Subjects given Linagliptin
|
Sugar Pill
n=22 participants at risk
Subjects given sugar pill/placebo
Placebo
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
Leg blisters
|
5.3%
1/19 • Number of events 1 • 12 weeks
whole study period
|
0.00%
0/22 • 12 weeks
whole study period
|
|
Renal and urinary disorders
acute kidney injury
|
0.00%
0/19 • 12 weeks
whole study period
|
4.5%
1/22 • 12 weeks
whole study period
|
|
Social circumstances
Car accident
|
0.00%
0/19 • 12 weeks
whole study period
|
4.5%
1/22 • 12 weeks
whole study period
|
|
Renal and urinary disorders
Decreased eGFR
|
0.00%
0/19 • 12 weeks
whole study period
|
4.5%
1/22 • 12 weeks
whole study period
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
5.3%
1/19 • 12 weeks
whole study period
|
0.00%
0/22 • 12 weeks
whole study period
|
Other adverse events
| Measure |
Linagliptin
n=19 participants at risk
Subjects given Linagliptin
|
Sugar Pill
n=22 participants at risk
Subjects given sugar pill/placebo
Placebo
|
|---|---|---|
|
Renal and urinary disorders
Increased creatinine and BUN, reduced GFR
|
5.3%
1/19 • 12 weeks
whole study period
|
13.6%
3/22 • 12 weeks
whole study period
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
5.3%
1/19 • 12 weeks
whole study period
|
0.00%
0/22 • 12 weeks
whole study period
|
|
Musculoskeletal and connective tissue disorders
Cramping in the calf muscle during the graded exercise test
|
0.00%
0/19 • 12 weeks
whole study period
|
4.5%
1/22 • Number of events 1 • 12 weeks
whole study period
|
|
Respiratory, thoracic and mediastinal disorders
Decreased CO2 concentration
|
0.00%
0/19 • 12 weeks
whole study period
|
4.5%
1/22 • 12 weeks
whole study period
|
|
Respiratory, thoracic and mediastinal disorders
Lung water accumulation
|
0.00%
0/19 • 12 weeks
whole study period
|
4.5%
1/22 • 12 weeks
whole study period
|
Additional Information
Aristidis Veves
Beth Israel deaconess Medical Center
Phone: 617 632 7075
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place