A Phase 4 interventional study of Saxagliptin and Placebo in Type 2 Diabetes, sponsored by George Washington University. Completed at 1 site in United States. Open to participants aged 40 Years to 70 Years. Per ClinicalTrials.gov, last updated 2019-02-15.
Sponsored by George Washington University · Phase 4, Interventional, and Treatment
Type 2 diabetes is a national epidemic. Diabetes has undesirable effects on blood vessels which may contribute to heart disease. Endothelial Progenitor Cells(EPCs) are found in the blood . Research has shown that improving the survival of these special blood cells may decrease the harmful effects of diabetes on blood vessels and reduce or reverse heart disease. Saxagliptin is an FDA(Food and Drug Administration) approved prescription medicine used along with diet and exercise to lower blood sugar in people with Type 2 diabetes. It is in a class of diabetes medication called DPP-4 inhibitors. DPP-4 inhibitors have been shown to increase EPCs in patients with Type 2 diabetes.
Hypothesis: We believe poor viability and function of EPCs in early diabetes ultimately affects the repair and regeneration of the endothelium and that prompt intervention using saxagliptin with another oral hypoglycemic agent, Metformin, may reduce or reverse cardiovascular risk by improving EPC survival and function above and beyond adequate glucose metabolism control.
Type 2 diabetes is a national epidemic 1,2 with significant macro and microvascular complications. Insulin resistance in prediabetes and early and late diabetes are associated with endothelial dysfunction.
A few studies indicate that EPCs can act as a suitable bio-marker for monitoring cardiovascular morbidity. In this proposal we suggest that EPCs or CD34 positive cells can act as a suitable cellular biomarker for estimating and following endothelial dysfunction in early type 2 diabetes patients.
EPCs have been used as a regenerative tool in ischemic myocardium and diabetic wound healing. Endothelial dysfunction with associated inflammation may be a consequence of excess super-oxide presence in a setting of diabetes which is a pro-oxidative stress condition causing EPC dysfunction and senescence. Therefore monitoring EPC number, function and gene expression may serve as a very useful cellular bio-marker for cardiovascular complications in early type 2 diabetes.
Though lifestyle modification has been proposed as a main stay for prevention and treatment of early type 2 diabetes, several new therapies for diabetes have been developed in recent years. Incretins and incretin mimetics appear to hold promise. Oral DPP-4 inhibitors have been shown to increase EPCs in patients with type 2 diabetes reportedly via SDF-1 alpha up-regulation. Interestingly, up-regulation of SDF-1 alpha and vascular endothelial growth factor (VEGF), both chemotactic factors increase mobilization and recruitment of EPCs in the face of acute ischemic injury for repair and regeneration.
Several studies have shown positive effect of incretins (Glucagon like peptide, GLP-1) and incretin receptor agonists (GLP-1 receptor agonists) on cardiovascular risk factors in type 2 diabetes patients and even in patients with chronic heart failure and left ventricular dysfunction who do not have diabetes.
DPP-4 Inhibitors may have cardio-protective effects of their own, as they increase bio-availability of endogenous GLP-1. They improve blood flow and nitric oxide production in endothelium. These are unique properties not demonstrated by other oral diabetes medications. The mechanism underlying these effects may be mediated by increased nitric oxide bioavailability but is not completely known. It is possible that Saxagliptin, a member of DPP-4 inhibitor group of drugs may be able to improve number and function of CD34+ endothelial progenitor cells by up-regulating chemotactic agent SDF1 alpha (DPP-4 degrades SDF-1) and its receptor CXCR47, 20, 21, 30, 31.
Poor viability and function of EPCs in early diabetes may ultimately affect the repair and regeneration of the endothelium and prompt intervention may reduce or reverse cardiovascular risk by improving EPC survival and function above and beyond adequate glucose metabolism control.
Therefore we would like to explore the effect of saxagliptin in addition to lifestyle intervention, on number and function and gene expression of EPC and impact on endothelial dysfunction in type 2 diabetes.
9,589 studies on the registry are indexed under Diabetes Mellitus, Type 2; 1,332 are open to participants now.
This study's enrollment of 42 is below the median of 81 across 7,713 interventional studies indexed under Diabetes Mellitus, Type 2.
Browse Diabetes Mellitus, Type 2 studies →George Washington University is the lead sponsor of 191 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.
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Exclusion Criteria:
Patients on low dose oral contraceptives will be allowed to participate as these formulations contain lesser amount of estrogens.
Matching placebo 1 pill daily for 12 weeks
Drug: Placebo
Saxagliptin 5mg once daily for 12 weeks
Drug: Saxagliptin
5 mg tablet once daily for 12 weeks
Also known as: Onglyza
1 tablet daily for 12 weeks
CD34+ Endothelial Progenitor Cells Number
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
Time frame: Up to 12 weeks post saxagliptin
CD 34+ Cell Function
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.
Time frame: 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
Serum Endothelial Inflammatory Marker hsCRP
Time frame: Baseline 6 and 12 weeks post saxagliptin
Fasting Lipid Profile LDL/HDL
ratio of LDL over HDL
Time frame: Baseline, 6 and 12 weeks post saxagliptin
Glycemic Control
measuring HbA1c levels
Time frame: Baseline, 6 and 12 weeks post saxagliptin
Adiposity
measured using a Tanita Body Composition Fat Analyzer scale, measured as percentage body fat
Time frame: Baseline, 6 and 12 weeks post saxagliptin
Arterial Stiffness
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.
Time frame: Baseline, 6 and 12 weeks post saxagliptin
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.
| Milestone | Placebo | Saxagliptin |
|---|---|---|
| Started | 21 | 21 |
| Completed | 21 | 21 |
| Not completed | 0 | 0 |
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
| % of Mononuclear Cells | Placebo | Saxagliptin |
|---|---|---|
| CD34+ Endothelial Progenitor Cells Number | 2.0 ± 0.3 | 2.8 ± 0.5 |
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.
| Ratio | Placebo | Saxagliptin |
|---|---|---|
| Visit 1 - Week 0 | 1.2 ± 0.1 | 1.05 ± 0.06 |
| Visit 2 - Week 6 | 1.05 ± 0.15 | 1.55 ± 0.2 |
| Visit 3 - Week 12 | 1.0 ± 0.06 | 1.2 ± 0.05 |
| mg/L | Placebo | Saxagliptin |
|---|---|---|
| Visit 1 - Baseline | 2.4 ± 0.6 | 2.8 ± 0.5 |
| Visit 2 - Week 6 | 2.9 ± 0.8 | 2.7 ± 0.4 |
| Visit 3 - Week 12 | 2.9 ± 0.7 | 2.4 ± 0.4 |
ratio of LDL over HDL
| ratio of LDL over HDL | Placebo | Saxagliptin |
|---|---|---|
| Visit 1 - Baseline | 2.3 ± 0.2 | 1.8 ± 0.1 |
| Visit 2 - Week 6 | 2.1 ± 0.2 | 1.8 ± 0.1 |
| Visit 3 - Week 12 | 2.1 ± 0.2 | 1.8 ± 0.2 |
measuring HbA1c levels
| % of Glycosylated Hemoglobin | Placebo | Saxagliptin |
|---|---|---|
| Visit 1 - Baseline | 6.6 ± 0.1 | 7.0 ± 0.2 |
| Visit 2 - Week 6 | 6.6 ± 0.1 | 6.8 ± 0.2 |
| Visit 3 - Week 12 | 6.5 ± 0.1 | 6.7 ± 0.2 |
measured using a Tanita Body Composition Fat Analyzer scale, measured as percentage body fat
| % of Body fat | Placebo | Saxagliptin |
|---|---|---|
| Visit 1 - Baseline | 34 ± 2 | 37 ± 2 |
| Visit 2 - Week 6 | 34 ± 2 | 36.5 ± 2 |
| Visit 3 - Week 12 | 35 ± 2 | 36 ± 2 |
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.
| Augmentation Index | Placebo | Saxagliptin |
|---|---|---|
| Visit 1: Baseline | 18.4 ± 2.4 | 24.1 ± 2.1 |
| Visit 2: Week 6 | 26 ± 3.9 | 22.5 ± 2.0 |
| Visit 3: Week 12 | 23.3 ± 2.3 | 23.1 ± 2.1 |
Collected over 20 weeks. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Placebo | 0/21 (0%) | 1/21 (4.8%) | 0/21 (0%) |
| Saxagliptin | 0/21 (0%) | 1/21 (4.8%) | 0/21 (0%) |
| Event | Placebo | Saxagliptin |
|---|---|---|
| Hypertensive UrgencyCardiac disorders | 1/21 | 0/21 |
| Chest PainCardiac disorders | 0/21 | 1/21 |
| Age, Continuous(years) | Placebo | Saxagliptin | Total |
|---|---|---|---|
| Mean | 56.4 ± 8.5 | 58.3 ± 5.7 | 57.3 ± 7.1 |
| Sex: Female, Male(Participants) | Placebo | Saxagliptin | Total |
|---|---|---|---|
| Female | 7 | 11 | 18 |
| Male | 14 | 10 | 24 |
| Race/Ethnicity, Customized(Participants) | Placebo | Saxagliptin | Total |
|---|---|---|---|
| African American | 13 | 15 | 28 |
| White | 6 | 5 | 11 |
| Other | 2 | 1 | 3 |
| Weight(Kg) | Placebo | Saxagliptin | Total |
|---|---|---|---|
| Mean | 202.3 ± 38.7 | 202.7 ± 24.5 | 202.5 ± 31.6 |
| BMI(kg/m^2) | Placebo | Saxagliptin | Total |
|---|---|---|---|
| Mean | 31.5 ± 4.8 | 32.3 ± 4.2 | 31.9 ± 4.5 |
| Duration of Diabetes Mellitus II(Years) | Placebo | Saxagliptin | Total |
|---|---|---|---|
| Mean | 3.5 ± 1.8 | 3.7 ± 2.4 | 3.6 ± 2.1 |
| HBA1c(mmol/mol) | Placebo | Saxagliptin | Total |
|---|---|---|---|
| Mean | 6.6 ± 0.5 | 7.0 ± 0.8 | 6.8 ± 0.65 |
| Fasting Glucose(mg/Dl) | Placebo | Saxagliptin | Total |
|---|---|---|---|
| Mean | 114.8 ± 25 | 127.4 ± 35.9 | 121.1 ± 30.45 |
1 further baseline measures are reported on the registry.
Documents are hosted by the registry — open the source record to download them.
Plan to share: No — There is no current plan for sharing IPD with other researchers.
The record gives a start of Nov 2013, a primary completion of Sep 2017 and a completion of Dec 2017. It does not say whether these dates are actual or estimated.
Results were first posted in Jan 2019, 1 year 4 months after primary completion.
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This study is completed, as verified in Jan 2019. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Saxagliptin
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