Effect of Sitagliptin on Endothelial Progenitor Cells

This study has been completed.
Sponsor:
Information provided by:
University of Padova
ClinicalTrials.gov Identifier:
NCT00968006
First received: August 26, 2009
Last updated: April 2, 2010
Last verified: April 2010
  Purpose

Endothelial progenitor cells (EPCs) are involved in cardiovascular homeostasis, through angiogenesis and endothelial healing. Diabetic patients have a high risk of cardiovascular events and low levels of circulating EPCs.

Sitagliptin is an oral DPP-IV antagonist, approved for the treatment of type 2 diabetes. It increases the bioavailability of endogenous incretins, thus improving insulin and glucagon secretion. SDF-1, one of the major EPC regulators, is also a substrate of DPP-IV. This study tests the hypothesis that sitagliptin increases the levels of circulating EPCs in type 2 diabetic patients.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Sitagliptin
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Effects of 4-week Sitagliptin Therapy on Endothelial Progenitor Cells in Type 2 Diabetic Patients. A Non-randomized Controlled Open-label Pilot Trial.

Resource links provided by NLM:


Further study details as provided by University of Padova:

Primary Outcome Measures:
  • Change in circulating CD34+KDR+ endothelial progenitor cells [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in SDF-1alpha concentrations [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Enrollment: 40
Study Start Date: October 2009
Study Completion Date: January 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment
Sitagliptin 100 mg once daily for 4 weeks
Drug: Sitagliptin
100 mg once daily for 4 weeks
Other Name: Januvia; Xelevia; Tesavel
No Intervention: Control
No change in anti-diabetic treatment regimen for at least 4 weeks.

Detailed Description:

Diabetic patients suffer an elevated wirk of cardiovascular events, which strongly impact on morbidity and mortality. The mechanisms that lead to cardiovascular disease in diabetes include alterations in the endothelial layer, due to hyperglycemia, oxidative stress and other associated abnormalities. Endothelial progenitor cells (EPCs) are bone marrow-derived cells involved in endothelial repair after injury, and they have been found to be reduced in diabetic patients. Thus, reduced EPCs in diabetes may be another mechanism of vascular disease induction. Reduction of EPCs in diabetes is attributable at least in part to the impairment of bone marrow mobilization, which is regulated by the chemokine SDF-1alpha, among others.

The oral hypoglycemia agent sitagliptin is a dipeptidyl dipeptidase-IV inhibitor, which prevents degradation of endogenous incretins (GIP and GLP-1), thus re-equilibrating insulin and glucagon secretion. Sitagliptin may also increase the concentrations of SDF-1alpha, which is another substrate of DPP-IV. The hypothesis is that sitagliptin may increase circulating EPC levels, through SDF-alpha.

This is going to be a pilot, non-randomized controlled 4-week trial of 100 mg oral sitagliptin therapy added to metformin/sulphonylureas in poorly controlled type 2 diabetic patients. At baseline and 4 weeks after the initiation of therapy blood samples will be drawn for the determination of circulating EPC levels, and concentrations of SDF-1alpha. EPCs will be defined as CD34+KDR+ cells and measured by flow cytometry as previously described in detail. SDF-1alpha will be measured using ELISA kits according to the manufacturer's instructions.

Changes between baseline and 4 weeks will be evaluated using two-tailed paired Student's t test and statistical significance accepted at p<0.05.

  Eligibility

Ages Eligible for Study:   40 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Type 2 diabetes;
  • Both genders
  • Age 40-80
  • fasting c-peptide >=1.0 ng/L
  • Therapy with metformin or sulphonylureas
  • HbA1c >7.0%
  • No contraindications to sitagliptin use

Exclusion Criteria:

  • Type 1 diabetes
  • Age <40 or >80
  • fasting c-peptide <1.0 ng/L
  • Therapy with TZD
  • HbA1c <=7.0%
  • Acute concomitant diseases
  • Immunological disorders
  • Recent (within 3 months) cardiovascular events or surgery
  • Pregnancy and lactation
  • Inability to provide informed consent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00968006

Locations
Italy
University of Padova, Medical School
Padova, Italy, 35100
Sponsors and Collaborators
University of Padova
Investigators
Principal Investigator: Angelo Avogaro, MD PhD Dept. Clinical and Experimental Medicine, University of Padova, Medical School, Padova (Italy)
  More Information

Publications:
Responsible Party: Angelo Avogaro, Associate Professor (PI), Dept Clinical and Experimental Medicine, University of Padova Medical School
ClinicalTrials.gov Identifier: NCT00968006     History of Changes
Other Study ID Numbers: Sita-EPC
Study First Received: August 26, 2009
Last Updated: April 2, 2010
Health Authority: Italy: Institutional Review Board and Ethic Committee
Italy: Ministry of Health

Keywords provided by University of Padova:
diabetes
endothelium
stem cells

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Sitagliptin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 01, 2014