CompletedNCT02964585Updated Dec 7, 2022Results posted

Role of Canagliflozin on CD34+ Cells in Patients With Type 2 Diabetes

A Phase 4 interventional study of Canagliflozin and Placebo in Type 2 Diabetes Mellitus, sponsored by George Washington University. Completed at 1 site in United States. Open to participants aged 30 Years to 70 Years. Per ClinicalTrials.gov, last updated 2022-12-07.

Sponsored by George Washington University · Phase 4, Interventional, and Treatment

Phase: Phase 4
Study type: Interventional
Enrollment: 34
Allocation: Randomized
Ages: 30 Years to 70 Years
Sex: All

Study summary

The investigators hypothesize that Cana may be able to improve number and function of CD34+ endothelial progenitor cells. The investigators also propose that this expected cardiovascular benefit is independent of HbA1C reduction.

Subjects will begin taking 100 mg of Cana or placebo after initial 4 weeks. Subjects will be withdrawn from the study if the medication or placebo is not tolerated.

Read the detailed description

Diabetes affects more than 11% of adults in the United States and this is projected to nearly double by 2025. Both diabetes and obesity are associated with endothelial dysfunction, oxidative stress, endothelial cell inflammation, cardiovascular pro-thrombotic states and are the most common causes of kidney disease. Use of a sodium-glucose linked transporter (SGLT-2) inhibitor has shown promise in improving glycemic control, weight reduction, hypertension and even changes in circulating Renin-angiotensin-aldosterone system (RAAS) and nitric oxide (NO). However, whether these group of drugs have any effect on cardiovascular disease (CVD) risk modification or on endothelium or endothelial progenitor cells as a surrogate of cardiovascular and renal risk outcome measure, is unclear.

The investigators have previously shown that CD34+ cells, derived from peripheral blood can act as a cellular biomarker that is more reliable than serum based markers for CVD risk estimation. Serum based inflammatory markers are not useful until the endothelium is already damaged and inflamed. Such serum based biomarkers takes several months to change and gives no preventive and predictable information as to whether a particular medication may affect future endothelium. This is why the study of endothelium progenitors is crucial. In the investigators' previous study of a prediabetes population with an aerobic exercise intervention, the investigators have demonstrated that CD34+ cells are responsive to a change in therapy or intervention within 2-4 weeks and can be used as a reliable non serum based cellular bio-marker. CD34+ cells or endothelial progenitor cells have been used clinically to improve collateral circulation and have been extensively studied as a robust cardiovascular biomarker. Therefore studying CD34+ cells in patients, with or without Canagliflozin (Cana) can give vital information about the medication and its effect on endothelium. This is particularly important as another SGLT2 inhibitor Empagliflozin has shown unparalleled positive cardiovascular effects with an oral hypoglycemic agent. Of course, the question arises whether this clinical trial effect is secondary to glucose effect or direct effect of SGLT2 inhibitor on endothelium.

Multiple glucose transporters have been identified in human cells these include GLUTs, SGLTs and even taste receptors (such as TLR2 and TLR3). The investigators know SGLT transporters are present in tubular cells and clearly blocking of SGLT2 in these cells is beneficial. Information on glucose transporter in stem or progenitor cells is almost nil. In our lab the investigators have shown presence of GLUT1, SGLTs and TLR3 on CD34+ cells. The investigators have also demonstrated that hyperglycemia is toxic to CD34+ cells, more than CD31+ positive mature endothelial cells. The investigators hypothesize that blocking SGLT2 in CD34+ cells will be beneficial rather than detrimental. As far as glucose uptake in CD34+ cells are concerned other glucose transporters should be sufficient, in fact lesser amount of glucose entry in a hyperglycemic milieu (type 2 DM patients) may be less pro-inflammatory and less pro-apoptotic.

Our preliminary data indicates that mRNA gene expression of both SGLT1 and SGLT2 are noted on human CD34+ cells however only SGLT2 mRNA gene expression is up-regulated several fold in human CD34+ cells in presence of hyperglycemia (20mM glucose). However non primary commercially obtained human endothelium (HUVEC) do not show similar results. An explanation could be SGLT2 expression decreases as the cell transitions from progenitor to mature endothelium. From these results the investigators believe SGLT2 inhibitor will be effective on progenitors and not mature endothelium. The investigators therefore hypothesize that CD34+ cells will be an ideal biomarker to study the effect of the drug. It is possible that Cana, by blocking SGLT2 receptors, may influence other CD34+ cell surface receptors including other glucose transporters and influence its function (most importantly migration). If a particular medication positively influences stem/progenitor cell migration then that medication can positively influence endothelial dysfunction and vascular complications from diabetes. The investigators are particularly interested to note effect of Canagliflozin, a SGLT2 inhibitor on other glucose transporters such as GLUT 1 and 4 while looking at SGLT 1 and 2 on CD34+ cells. It will be helpful to discern these effects particularly when choice of oral diabetic medication in a type 2 diabetes population is practically limited to metformin, DPP4 inhibitors and SGLT2 inhibitors. The investigators plan to investigate the effect of Cana on CD34+ cells, in a placebo matched study. The investigators plan to recruit subjects with type 2 diabetes with the following characteristics: 1) overweight, mild and moderately obese (BMI=25.0-39.9); 2) individuals with early type 2 diabetes (≤15 years) with inadequate control, HbA1C= 7.0 to 10.0%, on Metformin (1-2 grams/day) 3) with no history or presence of macrovascular complication and CKD no higher than stage 2. The subjects will be on Metformin as per ADA, Metformin is the 1st line of care along with life-style modification. While Metformin on its own may affect inflammatory biomarkers, the effect is minimal at best, particularly in presence of CKD and endothelial dysfunction. Also both placebo and the cana group will be on Metformin.

The investigators will recruit a total of 40 patients (20 individuals/per group) with approximately a 20% drop out rate over two years and the investigators hope to retain 32 individuals (16/group). Individuals in each group will be matched by sex, age, and race. Participants will be assessed at baseline (week 0), and at 2 and 4 months of drug intake.

Conditions studied

Type 2 Diabetes Mellitus

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Keywords

Type 2 Diabetes Mellitus
Endothelial Cells
Cellular Biomarker
Endothelial Dysfunction
CD34+
Impaired renal function

In context

Diabetes Mellitus

10,925 studies on the registry are indexed under Diabetes Mellitus; 1,319 are open to participants now.

This study's enrollment of 34 is below the median of 80 across 8,367 interventional studies indexed under Diabetes Mellitus.

Browse Diabetes Mellitus studies →

Lead sponsor

George Washington University is the lead sponsor of 187 studies on the registry; 34 are open to participants now.

Of its 13 completed or terminated interventional studies of FDA-regulated products, 11 (85%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 30 Years to 70 Years
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Age 30-70 years
Currently treated with any combination of the following anti-diabetic therapies: metformin (1-2 grams), insulin, GLP-1 agonists, a DPP-IV inhibitor, or sulfonylureas
Hemoglobin A1C (HbA1C) between 7.0% and 10.0%
Body Mass Index (BMI) between 25 and 39.9 kg/m\^2 (both inclusive)

Exclusion criteria

Exclusion Criteria:

Type 1 diabetes
History of hyperosmolar nonketotic coma
History of diabetic ketoacidosis in the last 3 months
Abnormal CBC that is judged by physician to be unsafe to enroll or low hematocrit (\<28 UNITS).
History of pancreatitis
History of diabetic ketoacidosis in the last 3 months
History of cancer (except basal cell carcinoma and cancer that is cured or not active or being treated in the past 5 years)
Heart attack or stroke within 6 months of screening
Clinically significant coronary and/or peripheral vascular disease that would be unsafe to enroll in the study.
Statin use started or dose change in the last 3 months
CKD Stages 3,4 and 5
Use of oral or injectable anti-diabetic medication other than any combination of the following anti-diabetic therapies: metformin (1-2 grams), insulin, GLP-1 agonists, a DPP-IV inhibitor, or sulfonylureas currently, or in the past 1 month.
Use of consistent long-term steroid medication (oral, inhaled, injected) within the last 3 months
Uncontrolled inflammatory disease, or current chronic use of anti-inflammatory drugs within the last 3 months. **This will be judged on a case by case basis by the PI**
Implanted devices (e.g., pacemakers) that may interact with Body Composition scale
Untreated Systolic Blood Pressure > 150 mmHg and diastolic Blood Pressure > 90 mmHg
Active wounds or recent surgery within 3 months
Untreated hyper/hypothyroidism

Physical and Laboratory Test Findings:

Pre-existing liver disease and/or ALT and AST >2.5X's UNL
Serum creatinine levels ≥2.0
Estimated CrCl \< 60 mL/min (measured by eGFR value)
Triglycerides >450 mg/dL

Allergies and Adverse Drug Reactions:

Subjects with a history of any serious hypersensitivity reaction to Cana or another SGLT2 inhibitor.

Sex and Reproductive Status:

Women in reproductive age group will be included in the study but encouraged to use contraceptive method to avoid pregnancy within 16 weeks of study duration.
Women who are pregnant or breast-feeding will be excluded.

Other Exclusion Criteria:

Prisoners or subjects who are involuntarily incarcerated.
Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness.
Patients who are active smokers
Patients who are pregnant
Nursing women
Post-menopausal women who are on estrogen hormone replacement therapy will be excluded.
Patients on low dose oral contraceptives will be allowed to participate as these formulations contain very low amounts of estrogens.
Eligibility criteria for this study have been carefully considered to ensure the safety of the study subjects and to ensure that the results of the study can be used. It is imperative that subjects fully meet all eligibility criteria.

Study design

Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double (Participant, Investigator)
Enrollment: 34 participants (actual)

Study arms

Active comparator
Active Arm
100 mg of Canagliflozin for 16 weeks
Drug: Canagliflozin
Placebo comparator
Placebo Arm
Placebo for 16 weeks
Drug: Placebo

Interventions

DrugCanagliflozin
100 mg
Also known as: INVOKANA
DrugPlacebo
1 tablet daily for 16 weeks

What researchers measure

Primary outcomes

Gene Expression and Function Change of CD34+ Endothelial Progenitor Cells (Protein Expression)
To determine whether 4 months of Canagliflozin modifies CD34+ cell number, gene expression and migration function. The investigators will obtain a total of approximately 95 mL of peripheral blood per visit. Of these 95 mL, 60-70 mL will be used to obtain CD34+ cells from mononuclear cell (MNC) population and 25-35 mL for biochemistry and plasma ELISA assays. MNC will be obtained from whole blood similar to protocols described before \[13,14\]. MNCs will be put through CD34 magnetic bead column to obtain CD34+ cells (Miltenyi Biotec). Purity of CD34+ cells, post sort, usually is above 90%, to be verified by FACS analysis.
Time frame: 16 weeks post Canagliflozin treatment reported
Gene Expression and Function Change of CD34+ Endothelial Progenitor Cells (Cell Percentages)
To determine whether 4 months of Canagliflozin modifies CD34+ cell number, gene expression and migration function. The investigators will obtain a total of approximately 95 mL of peripheral blood per visit. Of these 95 mL, 60-70 mL will be used to obtain CD34+ cells from mononuclear cell (MNC) population and 25-35 mL for biochemistry and plasma ELISA assays. MNC will be obtained from whole blood similar to protocols described before \[13,14\]. MNCs will be put through CD34 magnetic bead column to obtain CD34+ cells (Miltenyi Biotec). Purity of CD34+ cells, post sort, usually is above 90%, to be verified by FACS analysis.
Time frame: 16 weeks post Canagliflozin treatment reported
Gene Expression and Function Change of CD34+ Endothelial Progenitor Cells (Cell Counts)
To determine whether 4 months of Canagliflozin modifies CD34+ cell number, gene expression and migration function. The investigators will obtain a total of approximately 95 mL of peripheral blood per visit. Of these 95 mL, 60-70 mL will be used to obtain CD34+ cells from mononuclear cell (MNC) population and 25-35 mL for biochemistry and plasma ELISA assays. MNC will be obtained from whole blood similar to protocols described before \[13,14\]. MNCs will be put through CD34 magnetic bead column to obtain CD34+ cells (Miltenyi Biotec). Purity of CD34+ cells, post sort, usually is above 90%, to be verified by FACS analysis.
Time frame: 16 weeks post Canagliflozin treatment reported
Gene Expression and Function Change of CD34+ Endothelial Progenitor Cells (Cell Proliferation)
To determine whether 4 months of Canagliflozin modifies CD34+ cell number, gene expression and migration function. The investigators will obtain a total of approximately 95 mL of peripheral blood per visit. Of these 95 mL, 60-70 mL will be used to obtain CD34+ cells from mononuclear cell (MNC) population and 25-35 mL for biochemistry and plasma ELISA assays. MNC will be obtained from whole blood similar to protocols described before \[13,14\]. MNCs will be put through CD34 magnetic bead column to obtain CD34+ cells (Miltenyi Biotec). Purity of CD34+ cells, post sort, usually is above 90%, to be verified by FACS analysis.
Time frame: 16 weeks post Canagliflozin treatment reported

Secondary outcomes

Serum Endothelial Inflammatory Markers (1)
IL-6, and TNF-alpha
Time frame: measured at 8 and 16 (reported) weeks post treatment
Fasting Lipid Profile
Measured from a serum blood Lipid Panel: cholesterol and serum ketone bodies
Time frame: 16 weeks post Canagliflozin treatment reported (also measured at 8 weeks)
Glycemic Control (HbA1C)
As determined by HbA1C values
Time frame: 16 weeks post Canagliflozin treatment reported
BMI
Determined as weight in kg divided by height in meters squared
Time frame: 16 weeks post Canagliflozin treatment
Resting Metabolic Rate (RMR)
Using ReeVue (trademark) machine, with or without SGLT2 inhibitor therapy to ascertain if Cana has any effect on RMR. Other related trials have shown weight loss but effect on metabolic rate has not been studied .
Time frame: 16 weeks post Canagliflozin treatment
Pulse Wave Velocity
Vessel health assessed by using arterial tonometry with the SphygmoCor CP system from ATCOR .
Time frame: 16 weeks post Canagliflozin treatment reported (also measured at 8 weeks)
Serum Endothelial Inflammatory Markers (2)
Highly selective C-reactive protein (hs-CRP)
Time frame: measured at 8 and 16 (reported) weeks post treatment
Glycemic Control
Measured from blood glucose values (fasting) during visit
Time frame: 16 weeks post Canagliflozin treatment reported
Body Fat Percentage
Measured using a Tanita body composition scale
Time frame: 16 weeks post Canagliflozin treatment
Augmentation Index (Pulse Wave Analysis)
Vessel health assessed by using arterial tonometry with the SphygmoCor CP system from ATCOR. Higher values generally correlate with increased cardiovascular risk.
Time frame: 16 weeks post Canagliflozin treatment reported (also measured at 8 weeks)
Kidney Function Markers
Creatinine Clearance and Kidney Function measured from compiled results from a urine sample and blood tests
Time frame: 16 weeks post Canagliflozin treatment reported
Creatinine (Urine)
Creatinine Clearance and Kidney Function measured from compiled results from a urine sample and blood tests
Time frame: 16 weeks post Canagliflozin treatment reported
Microalbumin
Creatinine Clearance and Kidney Function measured from compiled results from a urine sample and blood tests
Time frame: 16 weeks post Canagliflozin treatment reported
eGFR
Creatinine Clearance and Kidney Function measured from compiled results from a urine sample and blood tests
Time frame: 16 weeks post Canagliflozin treatment reported

Results

Posted Dec 7, 2022

Limitations and caveats

Limitations of our pilot study may include the relatively short 16-week Canagliflozin therapy, which may be inadequate to see significant changes in certain clinical and cellular parameters. This maybe also because of the small sample size. Further studies with a larger population and longer duration may be helpful to further define the mechanisms behind our findings.

Participant flow

Participant flow — Overall Study
Milestone	Active Arm	Placebo Arm
Started	15	14
Completed	15	14
Not completed	0	0

Outcome measures

PrimaryGene Expression and Function Change of CD34+ Endothelial Progenitor Cells (Protein Expression)

To determine whether 4 months of Canagliflozin modifies CD34+ cell number, gene expression and migration function. The investigators will obtain a total of approximately 95 mL of peripheral blood per visit. Of these 95 mL, 60-70 mL will be used to obtain CD34+ cells from mononuclear cell (MNC) population and 25-35 mL for biochemistry and plasma ELISA assays. MNC will be obtained from whole blood similar to protocols described before \[13,14\]. MNCs will be put through CD34 magnetic bead column to obtain CD34+ cells (Miltenyi Biotec). Purity of CD34+ cells, post sort, usually is above 90%, to be verified by FACS analysis.

Time frame:: 16 weeks post Canagliflozin treatment reported
Reported as:: Mean · ng/mL in serum

Gene Expression and Function Change of CD34+ Endothelial Progenitor Cells (Protein Expression)
ng/mL in serum	Active Arm	Placebo Arm
CXCL12 Expression	0.63 ± 0.18	0.33 ± 0.17
CXCR4 Expression	1.58 ± 0.18	0.90 ± 0.18
EDN1	2.10 ± 0.27	1.03 ± 0.29
VEGEF-A	1.12 ± 0.19	0.83 ± 0.19
PECAM	1.28 ± 0.12	0.89 ± 0.12
KDR	1.16 ± 0.2	0.5 ± 0.2
NOS3	0.34 ± 0.21	-0.25 ± 0.21
Catalase	0.20 ± 0.26	-0.61 ± 0.26
GPX35	2.25 ± 0.54	1.71 ± 0.54
SDF 10 NG	0.26 ± 0.03	0.23 ± 0.03
SOD2	1.36 ± 0.24	0.92 ± 0.24

PrimaryGene Expression and Function Change of CD34+ Endothelial Progenitor Cells (Cell Percentages)

Time frame:: 16 weeks post Canagliflozin treatment reported
Reported as:: Mean · percentage of MNCs

Gene Expression and Function Change of CD34+ Endothelial Progenitor Cells (Cell Percentages)
percentage of MNCs	Active Arm	Placebo Arm
Percent of CD34+	0.93 ± 0.17	1.23 ± 0.21
Percent of CD31+	2.58 ± 0.35	2.16 ± 0.43
Percent CD34+ and CD184+	0.37 ± 0.09	0.61 ± 0.11

PrimaryGene Expression and Function Change of CD34+ Endothelial Progenitor Cells (Cell Counts)

Time frame:: 16 weeks post Canagliflozin treatment reported
Reported as:: Mean · cells*10^6/mL

Gene Expression and Function Change of CD34+ Endothelial Progenitor Cells (Cell Counts)
cells*10^6/mL	Active Arm	Placebo Arm
Mean MNC count	155.09 ± 15.54	155.09 ± 16.08
Mean CD34+ve cell count (x100)	2682.93 ± 491.44	3157.36 ± 508.69

PrimaryGene Expression and Function Change of CD34+ Endothelial Progenitor Cells (Cell Proliferation)

Time frame:: 16 weeks post Canagliflozin treatment reported
Reported as:: Mean · Colony forming units (CFU)

Gene Expression and Function Change of CD34+ Endothelial Progenitor Cells (Cell Proliferation)
Colony forming units (CFU)	Active Arm	Placebo Arm
Gene Expression and Function Change of CD34+ Endothelial Progenitor Cells (Cell Proliferation)	7.53 ± 1.89	13.69 ± 2.10

SecondarySerum Endothelial Inflammatory Markers (1)

IL-6, and TNF-alpha

Time frame:: measured at 8 and 16 (reported) weeks post treatment
Reported as:: Mean · pg/mL

Serum Endothelial Inflammatory Markers (1)
pg/mL	Active Arm	Placebo Arm
IL-6	4.56 ± 4.91	3.21 ± 1.82
TNF-alpha	1.36 ± 0.34	1.63 ± 0.53

SecondaryFasting Lipid Profile

Measured from a serum blood Lipid Panel: cholesterol and serum ketone bodies

Time frame:: 16 weeks post Canagliflozin treatment reported (also measured at 8 weeks)
Reported as:: Mean · mg/dL

Fasting Lipid Profile
mg/dL	Active Arm	Placebo Arm
Cholesterol	171.57 ± 9.84	147.76 ± 10.61
HDL	46.17 ± 3.48	51.67 ± 3.69
LDL	96.03 ± 6.93	82.672 ± 8.27
3-hydroxybutyric acid (ketone body)	0.02 ± 0.01	0.03 ± 0.01
Acetoacetic acid (ketone body)	0.69 ± 0.24	0.30 ± 0.27

SecondaryGlycemic Control (HbA1C)

As determined by HbA1C values

Time frame:: 16 weeks post Canagliflozin treatment reported
Reported as:: Mean · percentage of hemoglobin

Glycemic Control (HbA1C)
percentage of hemoglobin	Active Arm	Placebo Arm
Glycemic Control (HbA1C)	7.85 ± 1.66	8.26 ± 1.52

SecondaryBMI

Determined as weight in kg divided by height in meters squared

Time frame:: 16 weeks post Canagliflozin treatment
Reported as:: Mean · kg/m^2

BMI
kg/m^2	Active Arm	Placebo Arm
BMI	30.53 ± 1.29	34.64 ± 1.36

SecondaryResting Metabolic Rate (RMR)

Using ReeVue (trademark) machine, with or without SGLT2 inhibitor therapy to ascertain if Cana has any effect on RMR. Other related trials have shown weight loss but effect on metabolic rate has not been studied .

Time frame:: 16 weeks post Canagliflozin treatment
Reported as:: Mean · kcal/day

Resting Metabolic Rate (RMR)
kcal/day	Active Arm	Placebo Arm
Resting Metabolic Rate (RMR)	1999.31 ± 67.45	1863.01 ± 165.91

SecondaryPulse Wave Velocity

Vessel health assessed by using arterial tonometry with the SphygmoCor CP system from ATCOR .

Time frame:: 16 weeks post Canagliflozin treatment reported (also measured at 8 weeks)
Reported as:: Mean · m/s

Pulse Wave Velocity
m/s	Active Arm	Placebo Arm
Pulse Wave Velocity	10.12 ± 0.63	11.42 ± 0.70

SecondarySerum Endothelial Inflammatory Markers (2)

Highly selective C-reactive protein (hs-CRP)

Time frame:: measured at 8 and 16 (reported) weeks post treatment
Reported as:: Mean · mg/L

Serum Endothelial Inflammatory Markers (2)
mg/L	Active Arm	Placebo Arm
Serum Endothelial Inflammatory Markers (2)	0.63 ± 0.2	0.92 ± 0.2

SecondaryGlycemic Control

Measured from blood glucose values (fasting) during visit

Time frame:: 16 weeks post Canagliflozin treatment reported
Reported as:: Mean · mg/dL

Glycemic Control
mg/dL	Active Arm	Placebo Arm
Glycemic Control	142.79 ± 45.24	158.0 ± 38.4

SecondaryBody Fat Percentage

Measured using a Tanita body composition scale

Time frame:: 16 weeks post Canagliflozin treatment
Reported as:: Mean · percentage of body mass

Body Fat Percentage
percentage of body mass	Active Arm	Placebo Arm
Body Fat Percentage	32.46 ± 2.32	38.58 ± 2.63

SecondaryAugmentation Index (Pulse Wave Analysis)

Vessel health assessed by using arterial tonometry with the SphygmoCor CP system from ATCOR. Higher values generally correlate with increased cardiovascular risk.

Time frame:: 16 weeks post Canagliflozin treatment reported (also measured at 8 weeks)
Reported as:: Mean · percent aug pressure of pulse pressure

Augmentation Index (Pulse Wave Analysis)
percent aug pressure of pulse pressure	Active Arm	Placebo Arm
Augmentation Index (Pulse Wave Analysis)	28.67 ± 2.8	21.37 ± 3.2

SecondaryKidney Function Markers

Creatinine Clearance and Kidney Function measured from compiled results from a urine sample and blood tests

Time frame:: 16 weeks post Canagliflozin treatment reported
Reported as:: Mean · ug/dL

Kidney Function Markers
ug/dL	Active Arm	Placebo Arm
PODXL	6.62 ± 0.30	6.68 ± 0.4
Nephrin	5.24 ± 0.50	5.87 ± 0.65
Wilm's Tumor	5.75 ± 0.59	6.36 ± 0.75

SecondaryCreatinine (Urine)

Creatinine Clearance and Kidney Function measured from compiled results from a urine sample and blood tests

Time frame:: 16 weeks post Canagliflozin treatment reported
Reported as:: Mean · mmol/L

Creatinine (Urine)
mmol/L	Active Arm	Placebo Arm
Creatinine (Urine)	77.08 ± 15.58	106.23 ± 15.62

SecondaryMicroalbumin

Creatinine Clearance and Kidney Function measured from compiled results from a urine sample and blood tests

Time frame:: 16 weeks post Canagliflozin treatment reported
Reported as:: Mean · mg/g creatinine

Microalbumin
mg/g creatinine	Active Arm	Placebo Arm
Microalbumin	33.97 ± 13.24	43.41 ± 26.17

SecondaryeGFR

Creatinine Clearance and Kidney Function measured from compiled results from a urine sample and blood tests

Time frame:: 16 weeks post Canagliflozin treatment reported
Reported as:: Mean · mL/min

eGFR
mL/min	Active Arm	Placebo Arm
eGFR	79.90 ± 4.21	88.33 ± 4.52

Adverse events

Collected over Adverse event data was collected from signing of consent form to 30 days after last treatment day, approximately 20 weeks in total.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Active Arm	0/15 (0%)	0/15 (0%)	0/15 (0%)
Placebo Arm	0/14 (0%)	0/14 (0%)	0/14 (0%)

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Active Arm	Placebo Arm	Total
Mean	55.64 ± 7.75	59.15 ± 11.24	57.72 ± 9.65

Sex: Female, Male
Sex: Female, Male(Participants)	Active Arm	Placebo Arm	Total
Female	7	6	13
Male	8	8	16

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Active Arm	Placebo Arm	Total
American Indian or Alaska Native	0	0	0
Asian	4	1	5
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	6	9	15
White	5	4	9
More than one race	0	0	0
Unknown or Not Reported	0	0	0

Region of Enrollment
Region of Enrollment(participants)	Active Arm	Placebo Arm	Total
United States	15	14	29

BMI
BMI(kg/m^2)	Active Arm	Placebo Arm	Total
Mean	30.71 ± 1.41	33.11 ± 1.08	31.55 ± 0.92

Body Fat Percentage
Body Fat Percentage(percentage of body fat)	Active Arm	Placebo Arm	Total
Mean	32.92 ± 2.39	39.65 ± 2.64	36.14 ± 1.86

HbA1C
HbA1C(percentage of hemoglobin)	Active Arm	Placebo Arm	Total
Mean	8.39 ± 0.36	7.93 ± 0.33	8.14 ± 0.24

eGFR
eGFR(mL/min)	Active Arm	Placebo Arm	Total
Mean	80.24 ± 4.27	85.22 ± 4.43	82.43 ± 3.08

18 further baseline measures are reported on the registry.

Study locations

1 site

The George Washington University Medical Faculty Associates
Washington, District of Columbia 20037, United States

References and documents

Publications

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Department of Health and Human Services, NIH and National Center for Chronic Disease Prevention and Health Promotion, "National Diabetes Statistics: 2007 and 2011 Fact Sheet." 2011
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Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A, Bohm M, Nickenig G. Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med. 2005 Sep 8;353(10):999-1007. doi: 10.1056/NEJMoa043814. PubMed 16148285 ↗
Losordo DW, Schatz RA, White CJ, Udelson JE, Veereshwarayya V, Durgin M, Poh KK, Weinstein R, Kearney M, Chaudhry M, Burg A, Eaton L, Heyd L, Thorne T, Shturman L, Hoffmeister P, Story K, Zak V, Dowling D, Traverse JH, Olson RE, Flanagan J, Sodano D, Murayama T, Kawamoto A, Kusano KF, Wollins J, Welt F, Shah P, Soukas P, Asahara T, Henry TD. Intramyocardial transplantation of autologous CD34+ stem cells for intractable angina: a phase I/IIa double-blind, randomized controlled trial. Circulation. 2007 Jun 26;115(25):3165-72. doi: 10.1161/CIRCULATIONAHA.106.687376. Epub 2007 Jun 11. PubMed 17562958 ↗
Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE; EMPA-REG OUTCOME Investigators. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015 Nov 26;373(22):2117-28. doi: 10.1056/NEJMoa1504720. Epub 2015 Sep 17. PubMed 26378978 ↗
Nandula SR, Kundu N, Awal HB, Brichacek B, Fakhri M, Aimalla N, Elzarki A, Amdur RL, Sen S. Role of Canagliflozin on function of CD34+ve endothelial progenitor cells (EPC) in patients with type 2 diabetes. Cardiovasc Diabetol. 2021 Feb 13;20(1):44. doi: 10.1186/s12933-021-01235-4. PubMed 33581737 ↗

Study documents

Protocol and statistical analysis plan · Dec 15, 2017

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Dec 7, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02964585
Lead sponsor: George Washington University
Collaborators: Janssen Scientific Affairs, LLC
Responsible party: Sabyasachi Sen (Associate Professor of Medicine, George Washington University) — Principal investigator
First posted: Nov 16, 2016
Start date: Nov 2016
Primary completion: Jan 2020
Completion: Sep 2020
Results posted: Dec 7, 2022
Last update: Dec 7, 2022

Study contacts

Sabyasachi Sen, MD, PhD

principal investigator · Medical Faculty Associates

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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Role of Canagliflozin on CD34+ Cells in Patients With Type 2 Diabetes

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