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

NCT02024477 | Completed Phase 4 Results

• 1 other identifier: CV181-305
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Type 2 Diabetes

Keywords

endothelial cells; cellular biomarker; endothelial dysfunction

Outcome Measures

Primary Outcomes (2)

• 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

  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.

  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

Secondary Outcomes (5)

• Serum Endothelial Inflammatory Marker hsCRP

  Baseline 6 and 12 weeks post saxagliptin

• Fasting Lipid Profile LDL/HDL

  Baseline, 6 and 12 weeks post saxagliptin

• Glycemic Control

  Baseline, 6 and 12 weeks post saxagliptin

• Adiposity

  Baseline, 6 and 12 weeks post saxagliptin

• Arterial Stiffness

  Baseline, 6 and 12 weeks post saxagliptin

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Matching placebo 1 pill daily for 12 weeks

Drug: Placebo

saxagliptin

ACTIVE COMPARATOR

Saxagliptin 5mg once daily for 12 weeks

Drug: Saxagliptin

Interventions

Saxagliptin DRUG

5 mg tablet once daily for 12 weeks

Also known as: Onglyza

saxagliptin

Placebo DRUG

1 tablet daily for 12 weeks

Placebo

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults aged 40-70 years.
• Diagnosis of type 2 diabetes within the previous 8 years using criteria of the American Diabetes Association
• Currently treated with no hypoglycemic agents other than a stable dose (\>3 months) of metformin (≥1.0 to ≤2 grams daily).
• HbA1C between 6 to 9% (both inclusive)
• BMI 25 to 39.9 kg/m2 (both inclusive)

You may not qualify if:

• Contraindications for moderate exercise
• Implanted devices (e.g., pacemakers) that may interact with Tanita scale
• Previous coronary or cerebrovascular event within 6 months of screening or active or clinically significant coronary and/or peripheral vascular disease.
• Low hematocrit \<28 Units
• Pre-existing liver disease and/or ALT and AST \>2.5X's UNL
• Kidney disease (serum creatinine levels ≥1.5 mg/dL for men, ≥1.4 mg/dL for women,Creatinine Clearance ≤50 mL/min)
• History of pancreatitis, or cancer (except basal cell carcinoma)
• Statin use started (or dose change) in the last 3 months.
• Use of oral or injectable anti-diabetic medication other than Metformin
• Use of any form of consistent-long term steroid medication (oral, inhaled injected or nasal) within the last 3 months
• Systolic BP\> 140 mmHg and diastolic BP\> 90 mmHg
• Active wounds or recent surgery within 3 months.
• Inflammatory disease, or current use of anti-inflammatory drugs
• triglycerides \>400 mg/dL
• 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.

Sponsors & Collaborators

• George Washington University: lead
• AstraZeneca: collaborator

Study Sites (1)

Medical Faculty Associates Inc

Washington D.C., District of Columbia, 20037, United States

Location

Related Publications (1)

• Dore FJ, Domingues CC, Ahmadi N, Kundu N, Kropotova Y, Houston S, Rouphael C, Mammadova A, Witkin L, Khiyami A, Amdur RL, Sen S. The synergistic effects of saxagliptin and metformin on CD34+ endothelial progenitor cells in early type 2 diabetes patients: a randomized clinical trial. Cardiovasc Diabetol. 2018 May 3;17(1):65. doi: 10.1186/s12933-018-0709-9.

  PMID: 29724198 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

saxagliptin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Limitations and Caveats

Limitations of our study may include the relatively short duration of 12 week Saxagliptin therapy, which may have been inadequate to see significant changes in certain clinical and cellular parameters.

Results Point of Contact

• Title: Dr Saby Sen
• Organization: The George Washington University

ssen1@gwu.edu

202-994-8560

Study Officials

• Sabyaschi Sen, PhD, MD

  George Washington University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: December 13, 2013
• First Posted: December 31, 2013
• Study Start: November 1, 2013
• Primary Completion: September 1, 2017
• Study Completion: December 1, 2017
• Last Updated: February 15, 2019
• Results First Posted: January 29, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)