Trial Outcomes & Findings for Linagliptin's Effect on CD34+ Stem Cells (NCT NCT02467478)
NCT ID: NCT02467478
Last Updated: 2023-01-19
Results Overview
The investigators will use participants' peripheral blood derived CD34+ cells looking at number, function, and gene expression. Post Linagliptin will be compared to pre Linagliptin measurements. Here we report fold changes in protein populations as determined by ELISA.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
31 participants
Primary outcome timeframe
Week 12 expression as a fold difference to Week 0
Results posted on
2023-01-19
Participant Flow
Participant milestones
| Measure |
Placebo
Matching placebo 1 pill daily for 12 weeks
Placebo: 1 tablet daily for 12 weeks
|
Linagliptin
Linagliptin 5mg once daily for 12 weeks
Linagliptin: 5 mg tablet once daily for 12 weeks
|
|---|---|---|
|
Overall Study
STARTED
|
17
|
14
|
|
Overall Study
COMPLETED
|
17
|
14
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Values vary here as patients could be on either an insulin, metformin, or a combination of the two. As a result, some participants may be included in both analysis categories.
Baseline characteristics by cohort
| Measure |
Placebo
n=17 Participants
Matching placebo 1 pill daily for 12 weeks
Placebo: 1 tablet daily for 12 weeks
|
Linagliptin
n=14 Participants
Linagliptin 5mg once daily for 12 weeks
Linagliptin: 5 mg tablet once daily for 12 weeks
|
Total
n=31 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
|
63 years
STANDARD_DEVIATION 6 • n=5 Participants
|
61 years
STANDARD_DEVIATION 5 • n=7 Participants
|
62.09 years
STANDARD_DEVIATION 1.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
12 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
BMI
|
30.6 kg/m^2
STANDARD_DEVIATION 2.9 • n=5 Participants
|
31.2 kg/m^2
STANDARD_DEVIATION 4.4 • n=7 Participants
|
30.8 kg/m^2
STANDARD_DEVIATION .42 • n=5 Participants
|
|
HbA1c
|
7.4 percentage of hemoglobin
STANDARD_DEVIATION 1 • n=5 Participants
|
7.1 percentage of hemoglobin
STANDARD_DEVIATION 0.7 • n=7 Participants
|
7.26 percentage of hemoglobin
STANDARD_DEVIATION .21 • n=5 Participants
|
|
Required to be on stable dose of Metformin and/or Insulin
Metformin
|
14 participants
n=5 Participants • Values vary here as patients could be on either an insulin, metformin, or a combination of the two. As a result, some participants may be included in both analysis categories.
|
12 participants
n=7 Participants • Values vary here as patients could be on either an insulin, metformin, or a combination of the two. As a result, some participants may be included in both analysis categories.
|
26 participants
n=5 Participants • Values vary here as patients could be on either an insulin, metformin, or a combination of the two. As a result, some participants may be included in both analysis categories.
|
|
Required to be on stable dose of Metformin and/or Insulin
Insulin
|
6 participants
n=5 Participants • Values vary here as patients could be on either an insulin, metformin, or a combination of the two. As a result, some participants may be included in both analysis categories.
|
4 participants
n=7 Participants • Values vary here as patients could be on either an insulin, metformin, or a combination of the two. As a result, some participants may be included in both analysis categories.
|
10 participants
n=5 Participants • Values vary here as patients could be on either an insulin, metformin, or a combination of the two. As a result, some participants may be included in both analysis categories.
|
|
BP
Systolic
|
133 mmHg
STANDARD_DEVIATION 18 • n=5 Participants
|
128 mmHg
STANDARD_DEVIATION 10 • n=7 Participants
|
131 mmHg
STANDARD_DEVIATION 14 • n=5 Participants
|
|
BP
Diastolic
|
77 mmHg
STANDARD_DEVIATION 7 • n=5 Participants
|
81 mmHg
STANDARD_DEVIATION 7 • n=7 Participants
|
79 mmHg
STANDARD_DEVIATION 7 • n=5 Participants
|
|
Percent Fat
|
38 percentage
STANDARD_DEVIATION 10 • n=5 Participants
|
30 percentage
STANDARD_DEVIATION 10 • n=7 Participants
|
34 percentage
STANDARD_DEVIATION 10 • n=5 Participants
|
|
Waist cm
|
105 centimeters
STANDARD_DEVIATION 8 • n=5 Participants
|
107 centimeters
STANDARD_DEVIATION 17 • n=7 Participants
|
106 centimeters
STANDARD_DEVIATION 12 • n=5 Participants
|
|
Basal Metabolic Rate
|
1476 Calories/day
STANDARD_DEVIATION 448 • n=5 Participants
|
1868 Calories/day
STANDARD_DEVIATION 293 • n=7 Participants
|
1653 Calories/day
STANDARD_DEVIATION 134 • n=5 Participants
|
|
Fasting Glucose
|
130 mg/dl
STANDARD_DEVIATION 44 • n=5 Participants
|
125 mg/dl
STANDARD_DEVIATION 26 • n=7 Participants
|
127.5 mg/dl
STANDARD_DEVIATION 12.72 • n=5 Participants
|
|
Serum Creatinine
|
0.9 mg/dL
STANDARD_DEVIATION 0.3 • n=5 Participants
|
1.1 mg/dL
STANDARD_DEVIATION 0.4 • n=7 Participants
|
1 mg/dL
STANDARD_DEVIATION .07 • n=5 Participants
|
|
eGFR
|
84 mL/min/1.73m^2
STANDARD_DEVIATION 19 • n=5 Participants
|
83 mL/min/1.73m^2
STANDARD_DEVIATION 21 • n=7 Participants
|
83.5 mL/min/1.73m^2
STANDARD_DEVIATION 1.41 • n=5 Participants
|
|
Cholesterol
|
168 mg
STANDARD_DEVIATION 53 • n=5 Participants
|
166 mg
STANDARD_DEVIATION 52 • n=7 Participants
|
167 mg
STANDARD_DEVIATION .70 • n=5 Participants
|
PRIMARY outcome
Timeframe: Week 12 expression as a fold difference to Week 0The investigators will use participants' peripheral blood derived CD34+ cells looking at number, function, and gene expression. Post Linagliptin will be compared to pre Linagliptin measurements. Here we report fold changes in protein populations as determined by ELISA.
Outcome measures
| Measure |
Linagliptin
n=14 Participants
Linagliptin 5mg once daily for 12 weeks
Linagliptin: 5 mg tablet once daily for 12 weeks
|
Placebo
n=17 Participants
Matching placebo 1 pill daily for 12 weeks
Placebo: 1 tablet daily for 12 weeks
|
|---|---|---|
|
Cellular Markers
PECAM
|
2.48 Fold Change
Standard Deviation 2.80
|
1.48 Fold Change
Standard Deviation 1.11
|
|
Cellular Markers
VEGFA
|
2.4 Fold Change
Standard Deviation 2.91
|
1.43 Fold Change
Standard Deviation 1.2
|
|
Cellular Markers
SOD3
|
1.15 Fold Change
Standard Deviation 0.86
|
1.13 Fold Change
Standard Deviation 0.81
|
|
Cellular Markers
SOD2
|
2.47 Fold Change
Standard Deviation 4.27
|
1.40 Fold Change
Standard Deviation 1.34
|
|
Cellular Markers
GPX3
|
1.36 Fold Change
Standard Deviation 1.32
|
1.59 Fold Change
Standard Deviation 1.40
|
PRIMARY outcome
Timeframe: 12 weeks post beginning Linagliptin or placebo treatmentWe measure using microalbumin/creatinine ratio provided from a random spot urine sample.
Outcome measures
| Measure |
Linagliptin
n=14 Participants
Linagliptin 5mg once daily for 12 weeks
Linagliptin: 5 mg tablet once daily for 12 weeks
|
Placebo
n=17 Participants
Matching placebo 1 pill daily for 12 weeks
Placebo: 1 tablet daily for 12 weeks
|
|---|---|---|
|
Urinary Function Marker in CKD
|
39.70 ratio
Standard Deviation 68.92
|
51.12 ratio
Standard Deviation 99.55
|
SECONDARY outcome
Timeframe: 12 weeks post Linagliptin or Placebo treatmentSerum endothelial inflammatory markers included here: high sensitivity C-reactive protein (hs-CRP)
Outcome measures
| Measure |
Linagliptin
n=14 Participants
Linagliptin 5mg once daily for 12 weeks
Linagliptin: 5 mg tablet once daily for 12 weeks
|
Placebo
n=17 Participants
Matching placebo 1 pill daily for 12 weeks
Placebo: 1 tablet daily for 12 weeks
|
|---|---|---|
|
Serum Endothelial Inflammatory Markers
|
5.17 mg/L
Standard Deviation 6.54
|
3.08 mg/L
Standard Deviation 3.41
|
SECONDARY outcome
Timeframe: 12 weeks post Linagliptin or Placebo treatmentSerum endothelial inflammatory markers included here: Interleukin 6 (IL-6)
Outcome measures
| Measure |
Linagliptin
n=14 Participants
Linagliptin 5mg once daily for 12 weeks
Linagliptin: 5 mg tablet once daily for 12 weeks
|
Placebo
n=17 Participants
Matching placebo 1 pill daily for 12 weeks
Placebo: 1 tablet daily for 12 weeks
|
|---|---|---|
|
Serum Endothelial Inflammatory Markers
|
5.09 pg/mL
Standard Deviation 6.08
|
2.18 pg/mL
Standard Deviation 1.45
|
SECONDARY outcome
Timeframe: 12 weeks post beginning Linagliptin or placebo treatmentMeasured through serum biochemistry Lipid Panel
Outcome measures
| Measure |
Linagliptin
n=14 Participants
Linagliptin 5mg once daily for 12 weeks
Linagliptin: 5 mg tablet once daily for 12 weeks
|
Placebo
n=17 Participants
Matching placebo 1 pill daily for 12 weeks
Placebo: 1 tablet daily for 12 weeks
|
|---|---|---|
|
Fasting Lipid Profile
Cholesterol
|
159.69 mg/dl
Standard Deviation 48.53
|
171.45 mg/dl
Standard Deviation 48.49
|
|
Fasting Lipid Profile
Triglycerides
|
124.31 mg/dl
Standard Deviation 50.67
|
127.76 mg/dl
Standard Deviation 79.04
|
SECONDARY outcome
Timeframe: 12 weeks post beginning Linagliptin or placebo treatmentGlycemic control is evaluated by measuring HbA1c levels to gauge changes in blood sugar control over last \~90 days
Outcome measures
| Measure |
Linagliptin
n=14 Participants
Linagliptin 5mg once daily for 12 weeks
Linagliptin: 5 mg tablet once daily for 12 weeks
|
Placebo
n=17 Participants
Matching placebo 1 pill daily for 12 weeks
Placebo: 1 tablet daily for 12 weeks
|
|---|---|---|
|
Glycemic Control
|
6.66 percentage of hemoglobin
Standard Deviation 0.40
|
7.27 percentage of hemoglobin
Standard Deviation 0.73
|
SECONDARY outcome
Timeframe: 12 weeks post beginning Linagliptin or placebo treatmentGlycemic control is evaluated by measuring fasting blood glucose at time of measurement
Outcome measures
| Measure |
Linagliptin
n=14 Participants
Linagliptin 5mg once daily for 12 weeks
Linagliptin: 5 mg tablet once daily for 12 weeks
|
Placebo
n=17 Participants
Matching placebo 1 pill daily for 12 weeks
Placebo: 1 tablet daily for 12 weeks
|
|---|---|---|
|
Glycemic Control: Fasting Glucose
|
109.93 mg/dL
Standard Deviation 16.81
|
129.68 mg/dL
Standard Deviation 46.78
|
SECONDARY outcome
Timeframe: 12 weeks post beginning Linagliptin or placebo treatmentGlycemic control is evaluated by measuring insulin levels at the time of the visit
Outcome measures
| Measure |
Linagliptin
n=14 Participants
Linagliptin 5mg once daily for 12 weeks
Linagliptin: 5 mg tablet once daily for 12 weeks
|
Placebo
n=17 Participants
Matching placebo 1 pill daily for 12 weeks
Placebo: 1 tablet daily for 12 weeks
|
|---|---|---|
|
Glycemic Control: Insulin
|
20.52 mIU/L
Standard Deviation 19.7
|
20.82 mIU/L
Standard Deviation 12.6
|
SECONDARY outcome
Timeframe: 12 weeks post beginning Linagliptin or placebo treatmentMeasured using the Tanita Body Composition Analyzer scale, measured as percentage body fat.
Outcome measures
| Measure |
Linagliptin
n=14 Participants
Linagliptin 5mg once daily for 12 weeks
Linagliptin: 5 mg tablet once daily for 12 weeks
|
Placebo
n=17 Participants
Matching placebo 1 pill daily for 12 weeks
Placebo: 1 tablet daily for 12 weeks
|
|---|---|---|
|
Adiposity
|
31.2 percentage of body fat
Standard Deviation 4.4
|
30.6 percentage of body fat
Standard Deviation 2.9
|
SECONDARY outcome
Timeframe: 12 weeks post beginning Linagliptin or placebo treatmentMeasured via blood biochemistry eGFR, an alternative measurement to spot urine urine microalbumin/creatinine ratio presented above
Outcome measures
| Measure |
Linagliptin
n=14 Participants
Linagliptin 5mg once daily for 12 weeks
Linagliptin: 5 mg tablet once daily for 12 weeks
|
Placebo
n=17 Participants
Matching placebo 1 pill daily for 12 weeks
Placebo: 1 tablet daily for 12 weeks
|
|---|---|---|
|
Estimation of Creatinine Clearance
|
79.46 mL/min/1.73m^2
Standard Deviation 19.9
|
84.12 mL/min/1.73m^2
Standard Deviation 19.81
|
SECONDARY outcome
Timeframe: 12 weeks post beginning Linagliptin or placebo treatmentVessel health is assessed by looking at Arterial stiffness. Augmentation index (AI) is defined as the ratio of the augmentation pressure to the pulse pressure, times 100, to give a percentage. Augmentation index 75 normalizes this value to an estimate of the AI at a heart rate of 75bpm. We used Vascular Flow and wave measurement equipment, SphygmoCor Central Pressure system from AtCor.
Outcome measures
| Measure |
Linagliptin
n=14 Participants
Linagliptin 5mg once daily for 12 weeks
Linagliptin: 5 mg tablet once daily for 12 weeks
|
Placebo
n=17 Participants
Matching placebo 1 pill daily for 12 weeks
Placebo: 1 tablet daily for 12 weeks
|
|---|---|---|
|
Pulse Wave Analysis
Augmentation Index 75
|
22.33 Percentage (of pulse pressure)
Standard Deviation 12
|
21.37 Percentage (of pulse pressure)
Standard Deviation 11.49
|
|
Pulse Wave Analysis
Augmentation Index
|
24.93 Percentage (of pulse pressure)
Standard Deviation 14.37
|
24.17 Percentage (of pulse pressure)
Standard Deviation 12.93
|
SECONDARY outcome
Timeframe: 12 weeks post beginning Linagliptin or placebo treatmentVessel health is assessed by looking at Arterial stiffness. Pulse wave velocity (PWV) measures the delay between the pulse registered at the femoral artery from the pulse at the carotid. The difference in distance between these two measurement points from the aortic notch is divided by this delay to give a speed. In stiffer, less healthy vessels, the PWV is increased. We used Vascular Flow and wave measurement equipment, SphygmoCor Central Pressure system from AtCor to perform this calculation.
Outcome measures
| Measure |
Linagliptin
n=14 Participants
Linagliptin 5mg once daily for 12 weeks
Linagliptin: 5 mg tablet once daily for 12 weeks
|
Placebo
n=17 Participants
Matching placebo 1 pill daily for 12 weeks
Placebo: 1 tablet daily for 12 weeks
|
|---|---|---|
|
Pulse Wave Velocity
|
10.53 m/s
Standard Deviation 8.58
|
10.23 m/s
Standard Deviation 8.65
|
SECONDARY outcome
Timeframe: 12 weeks post beginning Linagliptin or placebo treatment(RMR, similar to Resting Energy expenditure measurement): Evaluation of changes in Basal Metabolic Rate
Outcome measures
| Measure |
Linagliptin
n=14 Participants
Linagliptin 5mg once daily for 12 weeks
Linagliptin: 5 mg tablet once daily for 12 weeks
|
Placebo
n=17 Participants
Matching placebo 1 pill daily for 12 weeks
Placebo: 1 tablet daily for 12 weeks
|
|---|---|---|
|
Resting Metabolic Rate (RMR)
|
1657.6 Calories/day
Standard Deviation 445.45
|
1650.07 Calories/day
Standard Deviation 428.52
|
Adverse Events
Placebo
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Linagliptin
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=17 participants at risk
Matching placebo 1 pill daily for 12 weeks
Placebo: 1 tablet daily for 12 weeks
|
Linagliptin
n=14 participants at risk
Linagliptin 5mg once daily for 12 weeks
Linagliptin: 5 mg tablet once daily for 12 weeks
|
|---|---|---|
|
Renal and urinary disorders
Kidney Stone
|
5.9%
1/17 • Number of events 1 • Adverse event data was collected from signing of informed consent to 30 days post final visit (approximately 16 weeks)
The adverse events that occurred during the duration of the study were isolated incidents, therefore, do not have any relation to the study intervention or medication regiment.
|
7.1%
1/14 • Number of events 1 • Adverse event data was collected from signing of informed consent to 30 days post final visit (approximately 16 weeks)
The adverse events that occurred during the duration of the study were isolated incidents, therefore, do not have any relation to the study intervention or medication regiment.
|
|
Skin and subcutaneous tissue disorders
Bacterial Abscess
|
5.9%
1/17 • Number of events 1 • Adverse event data was collected from signing of informed consent to 30 days post final visit (approximately 16 weeks)
The adverse events that occurred during the duration of the study were isolated incidents, therefore, do not have any relation to the study intervention or medication regiment.
|
7.1%
1/14 • Number of events 1 • Adverse event data was collected from signing of informed consent to 30 days post final visit (approximately 16 weeks)
The adverse events that occurred during the duration of the study were isolated incidents, therefore, do not have any relation to the study intervention or medication regiment.
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place