Trial Outcomes & Findings for Effect of Saxagliptin on EPCs as a Cellular Biomarker for Evaluating Endothelial Dysfunction in Early T2DM Patients (NCT NCT02024477)

Results Overview

We will use patient's peripheral blood derived CD34+ cells looking at number of CD34+ Endothelial Progenitor Cell as % of the total Mononuclear cell population. Post saxagliptin will be compared to pre saxagliptin measurement

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

42 participants

Primary outcome timeframe

Up to 12 weeks post saxagliptin

Results posted on

2019-02-15

Participant Flow

Subjects were recruited from clinic of the Principle Investigator and Sub-Investigators involved in the trial. First patient was recruited on 26 Nov 2013, last patient was recruited on 24 May 2016.

Screening period lasted 2 weeks. No wash-out or run-in periods were necessary.

Participant milestones

Participant milestones
Measure	Placebo Placebo: 1 tablet daily for 12 weeks	Saxagliptin Saxagliptin: 5 mg tablet once daily for 12 weeks
Overall Study STARTED	21	21
Overall Study COMPLETED	21	21
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Effect of Saxagliptin on EPCs as a Cellular Biomarker for Evaluating Endothelial Dysfunction in Early T2DM Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=21 Participants Placebo: 1 tablet daily for 12 weeks	Saxagliptin n=21 Participants Saxagliptin: 5 mg tablet once daily for 12 weeks	Total n=42 Participants Total of all reporting groups
Age, Continuous	56.4 years STANDARD_DEVIATION 8.5 • n=5 Participants	58.3 years STANDARD_DEVIATION 5.7 • n=7 Participants	57.3 years STANDARD_DEVIATION 7.1 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	11 Participants n=7 Participants	18 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	10 Participants n=7 Participants	24 Participants n=5 Participants
Race/Ethnicity, Customized African American	13 Participants n=5 Participants	15 Participants n=7 Participants	28 Participants n=5 Participants
Race/Ethnicity, Customized White	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Race/Ethnicity, Customized Other	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Weight	202.3 Kg STANDARD_DEVIATION 38.7 • n=5 Participants	202.7 Kg STANDARD_DEVIATION 24.5 • n=7 Participants	202.5 Kg STANDARD_DEVIATION 31.6 • n=5 Participants
BMI	31.5 kg/m^2 STANDARD_DEVIATION 4.8 • n=5 Participants	32.3 kg/m^2 STANDARD_DEVIATION 4.2 • n=7 Participants	31.9 kg/m^2 STANDARD_DEVIATION 4.5 • n=5 Participants
Duration of Diabetes Mellitus II	3.5 Years STANDARD_DEVIATION 1.8 • n=5 Participants	3.7 Years STANDARD_DEVIATION 2.4 • n=7 Participants	3.6 Years STANDARD_DEVIATION 2.1 • n=5 Participants
HBA1c	6.6 mmol/mol STANDARD_DEVIATION 0.5 • n=5 Participants	7.0 mmol/mol STANDARD_DEVIATION 0.8 • n=7 Participants	6.8 mmol/mol STANDARD_DEVIATION 0.65 • n=5 Participants
Fasting Glucose	114.8 mg/Dl STANDARD_DEVIATION 25 • n=5 Participants	127.4 mg/Dl STANDARD_DEVIATION 35.9 • n=7 Participants	121.1 mg/Dl STANDARD_DEVIATION 30.45 • n=5 Participants
eGFR	93.7 mL/min/1.73 STANDARD_DEVIATION 16.7 • n=5 Participants	98.9 mL/min/1.73 STANDARD_DEVIATION 14.5 • n=7 Participants	96.3 mL/min/1.73 STANDARD_DEVIATION 15.6 • n=5 Participants

PRIMARY outcome

Timeframe: Up to 12 weeks post saxagliptin

We will use patient's peripheral blood derived CD34+ cells looking at number of CD34+ Endothelial Progenitor Cell as % of the total Mononuclear cell population. Post saxagliptin will be compared to pre saxagliptin measurement

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Placebo: 1 tablet daily for 12 weeks	Saxagliptin n=21 Participants Saxagliptin: 5 mg tablet once daily for 12 weeks
CD34+ Endothelial Progenitor Cells Number	2.0 % of Mononuclear Cells Standard Deviation 0.3	2.8 % of Mononuclear Cells Standard Deviation 0.5

PRIMARY outcome

Timeframe: Up to 12 weeks post saxagliptin Up to 12 weeks post saxagliptin: Visit 1 at Baseline, Visit 2 at 6 weeks, and Visit 3 at 12 weeks

function of EPC cell as migration of CD34+ cells in response to SDF-1a ( 100 ng/mL). Results are expressed in fluorescence ratio between cells exposed to the chemotactic factor and cells exposed to chemo attractant-free media ( control) followed by lysis in presence of CyQuant GR dye.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Placebo: 1 tablet daily for 12 weeks	Saxagliptin n=21 Participants Saxagliptin: 5 mg tablet once daily for 12 weeks
CD 34+ Cell Function Visit 3 - Week 12	1.0 Ratio Standard Deviation 0.06	1.2 Ratio Standard Deviation 0.05
CD 34+ Cell Function Visit 1 - Week 0	1.2 Ratio Standard Deviation 0.1	1.05 Ratio Standard Deviation 0.06
CD 34+ Cell Function Visit 2 - Week 6	1.05 Ratio Standard Deviation 0.15	1.55 Ratio Standard Deviation 0.2

SECONDARY outcome

Timeframe: Baseline 6 and 12 weeks post saxagliptin

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Placebo: 1 tablet daily for 12 weeks	Saxagliptin n=21 Participants Saxagliptin: 5 mg tablet once daily for 12 weeks
Serum Endothelial Inflammatory Marker hsCRP Visit 1 - Baseline	2.4 mg/L Standard Deviation 0.6	2.8 mg/L Standard Deviation 0.5
Serum Endothelial Inflammatory Marker hsCRP Visit 2 - Week 6	2.9 mg/L Standard Deviation 0.8	2.7 mg/L Standard Deviation 0.4
Serum Endothelial Inflammatory Marker hsCRP Visit 3 - Week 12	2.9 mg/L Standard Deviation 0.7	2.4 mg/L Standard Deviation 0.4

SECONDARY outcome

Timeframe: Baseline, 6 and 12 weeks post saxagliptin

ratio of LDL over HDL

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Placebo: 1 tablet daily for 12 weeks	Saxagliptin n=21 Participants Saxagliptin: 5 mg tablet once daily for 12 weeks
Fasting Lipid Profile LDL/HDL Visit 1 - Baseline	2.3 ratio of LDL over HDL Standard Deviation 0.2	1.8 ratio of LDL over HDL Standard Deviation 0.1
Fasting Lipid Profile LDL/HDL Visit 2 - Week 6	2.1 ratio of LDL over HDL Standard Deviation 0.2	1.8 ratio of LDL over HDL Standard Deviation 0.1
Fasting Lipid Profile LDL/HDL Visit 3 - Week 12	2.1 ratio of LDL over HDL Standard Deviation 0.2	1.8 ratio of LDL over HDL Standard Deviation 0.2

SECONDARY outcome

Timeframe: Baseline, 6 and 12 weeks post saxagliptin

measuring HbA1c levels

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Placebo: 1 tablet daily for 12 weeks	Saxagliptin n=21 Participants Saxagliptin: 5 mg tablet once daily for 12 weeks
Glycemic Control Visit 1 - Baseline	6.6 % of Glycosylated Hemoglobin Standard Deviation 0.1	7.0 % of Glycosylated Hemoglobin Standard Deviation 0.2
Glycemic Control Visit 2 - Week 6	6.6 % of Glycosylated Hemoglobin Standard Deviation 0.1	6.8 % of Glycosylated Hemoglobin Standard Deviation 0.2
Glycemic Control Visit 3 - Week 12	6.5 % of Glycosylated Hemoglobin Standard Deviation 0.1	6.7 % of Glycosylated Hemoglobin Standard Deviation 0.2

SECONDARY outcome

Timeframe: Baseline, 6 and 12 weeks post saxagliptin

measured using a Tanita Body Composition Fat Analyzer scale, measured as percentage body fat

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Placebo: 1 tablet daily for 12 weeks	Saxagliptin n=21 Participants Saxagliptin: 5 mg tablet once daily for 12 weeks
Adiposity Visit 2 - Week 6	34 % of Body fat Standard Deviation 2	36.5 % of Body fat Standard Deviation 2
Adiposity Visit 3 - Week 12	35 % of Body fat Standard Deviation 2	36 % of Body fat Standard Deviation 2
Adiposity Visit 1 - Baseline	34 % of Body fat Standard Deviation 2	37 % of Body fat Standard Deviation 2

SECONDARY outcome

Timeframe: Baseline, 6 and 12 weeks post saxagliptin

Arterial stiffness assessed using Vascular Flow and wave measurement equipment, SphygmoCor CP system from ATCOR. Reported as Augmentation Index adjusted for a heart rate of 75. Augmentation index (AIx) is a measure of systemic arterial stiffness derived from the ascending aortic pressure waveform. Lower the value, better correlated outcome as positive augmentation represents stiffer artery.

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Placebo: 1 tablet daily for 12 weeks	Saxagliptin n=21 Participants Saxagliptin: 5 mg tablet once daily for 12 weeks
Arterial Stiffness Visit 1: Baseline	18.4 Augmentation Index Standard Deviation 2.4	24.1 Augmentation Index Standard Deviation 2.1
Arterial Stiffness Visit 2: Week 6	26 Augmentation Index Standard Deviation 3.9	22.5 Augmentation Index Standard Deviation 2.0
Arterial Stiffness Visit 3: Week 12	23.3 Augmentation Index Standard Deviation 2.3	23.1 Augmentation Index Standard Deviation 2.1

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Saxagliptin

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=21 participants at risk Placebo: 1 tablet daily for 12 weeks	Saxagliptin n=21 participants at risk Saxagliptin 5mg once daily for 12 weeks
Cardiac disorders Hypertensive Urgency	4.8% 1/21 • 20 weeks from the day ICF was signed till 1 month after V3.	0.00% 0/21 • 20 weeks from the day ICF was signed till 1 month after V3.
Cardiac disorders Chest Pain	0.00% 0/21 • 20 weeks from the day ICF was signed till 1 month after V3.	4.8% 1/21 • 20 weeks from the day ICF was signed till 1 month after V3.

Other adverse events

Adverse event data not reported

Additional Information

Dr Saby Sen

The George Washington University

Phone: 202-994-8560

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place