Overview

This trial is active, not recruiting.

Condition type 2 diabetes
Treatments saxagliptin, placebo
Phase phase 4
Sponsor George Washington University
Collaborator AstraZeneca
Start date November 2013
End date December 2016
Trial size 42 participants
Trial identifier NCT02024477, CV181-305

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose treatment
Arm
(Placebo Comparator)
Matching placebo 1 pill daily for 12 weeks
placebo
1 tablet daily for 12 weeks
(Active Comparator)
Saxagliptin 5mg once daily for 12 weeks
saxagliptin Onglyza
5 mg tablet once daily for 12 weeks

Primary Outcomes

Measure
Cellular marker. We will use patient's peripheral blood derived CD34+ cells looking at number, function and gene expression..
time frame: up to 12 weeks post saxagliptin

Secondary Outcomes

Measure
serum endothelial inflammatory markers
time frame: 6 and 12 weeks post saxagliptin
fasting lipid profile
time frame: 6 and 12 weeks post saxagliptin
Glycemic control
time frame: 6 and 12 weeks post saxagliptin
Adiposity
time frame: 6 and 12 weeks post saxagliptin
vessel health
time frame: 6 and 12 weeks post saxagliptin

Eligibility Criteria

Male or female participants from 40 years up to 70 years old.

Inclusion Criteria 1. Adults aged 40-70 years. 2. Diagnosis of type 2 diabetes within the previous 8 years using criteria of the American Diabetes Association 3. Currently treated with no hypoglycemic agents other than a stable dose (>3 months) of metformin (≥1.0 to ≤2 grams daily). 4. HbA1C between 6 to 9% (both inclusive) 5. BMI 25 to 39.9 kg/m2 (both inclusive) Exclusion Criteria: 1. Contraindications for moderate exercise 2. Implanted devices (e.g., pacemakers) that may interact with Tanita scale 3. Previous coronary or cerebrovascular event within 6 months of screening or active or clinically significant coronary and/or peripheral vascular disease. 4. Low hematocrit <28 Units 5. Pre-existing liver disease and/or ALT and AST >2.5X's UNL 6. Kidney disease (serum creatinine levels ≥1.5 mg/dL for men, ≥1.4 mg/dL for women,Creatinine Clearance ≤50 mL/min) 7. History of pancreatitis, or cancer (except basal cell carcinoma) 8. Statin use started (or dose change) in the last 3 months. 9. Use of oral or injectable anti-diabetic medication other than Metformin 10. Use of any form of consistent-long term steroid medication (oral, inhaled injected or nasal) within the last 3 months 11. Systolic BP> 140 mmHg and diastolic BP> 90 mmHg 12. Active wounds or recent surgery within 3 months. 13. Inflammatory disease, or current use of anti-inflammatory drugs 14. triglycerides >400 mg/dL 15. untreated hyper/hypothyroidism Additionally, patients who are active smokers, patients who are pregnant, nursing women, and post menopausal women who are on hormone replacement therapy will be excluded. Patients on low dose oral contraceptives will be allowed to participate as these formulations contain lesser amount of estrogens.

Additional Information

Official title Effect of Saxagliptin (DPP-4 Inhibitor) on Endothelial Progenitor Cells (EPCs) as a Cellular Biomarker for Evaluating Endothelial Dysfunction in Early Type 2 Diabetes Patients
Principal investigator Sabyaschi Sen, PhD, MD
Description Type 2 diabetes is a national epidemic 1,2 with significant macro and microvascular complications3. Insulin resistance in prediabetes and early and late diabetes are associated with endothelial dysfunction4. A few studies indicate that EPCs can act as a suitable bio-marker 5-7 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 8-13. 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 senescence14. 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, 2, 15-19 several new therapies for diabetes have been developed in recent years2. Incretins and incretin mimetics appear to hold promise. Oral DPP-4 inhibitors have been shown to increase EPCs in patients with type 2 diabetes 20 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.21-24. 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 patients20,25 and even in patients with chronic heart failure and left ventricular dysfunction who do not have diabetes26,27. 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 endothelium28, 29. These are unique properties not demonstrated by other oral diabetes medications 28. 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.
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by George Washington University.