Effect of Vildagliptin vs. Glibenclamide on Circulating Endothelial Progenitor Cell Number Type 2 Diabetes

Type 2 Diabetes Clinical Trial

Official title:

Randomized, Open Label, Two Parallel Arms, Intervention Trial Comparing the Effect of DPP-IV Inhibitor Vildagliptin vs. Glibenclamide on Circulating Endothelial Progenitor Cell Number in Patients With Type 2 Diabetes in Metformin Failure

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01822548
• Other study ID #: 2012-005399-32
• Status: Completed
• Phase: Phase 3
• First received: March 28, 2013
• Last updated: January 23, 2017
• Start date: October 2010
• Est. completion date: January 2015

Study information

• Verified date: January 2015
• Source: Azienda Ospedaliero-Universitaria di Parma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the effect of DPP-IV inhibitor Vildagliptin vs. Glibenclamide on circulating endothelial progenitor cells (EPCs) number in type 2 diabetes patients in metformin failure. Subjects will be followed for 12 months after randomization.

Description:

Diabetic patients show a higher cardiovascular risk compared with non-diabetic patients. It is therefore crucial that blood glucose lowering drugs reveal a favorable cardiovascular risk profile independently of metabolic control.

EPCs are a subset of circulating mononuclear cells derived from the bone marrow. EPCs play a fundamental role in the formation of new blood vessels (neo-endothelization) and repairing of existing blood vessels (re-endothelization) in order to maintain endothelial homeostasis and integrity. Endothelial damage and tissue ischemia, through the release of growth factors and cytokines, represent a strong stimulus for the mobilization of EPCs from the bone marrow. Reduced EPC number has been related to the presence of traditional risk factors for cardiovascular disease and to the development of atherosclerosis and has been shown to predict cardiovascular (CV)risk. Type 2 diabetes is known to be associated with an increased CV risk and a reduced EPC number. Recent data suggest that DDP-IV inhibitors might be involved in the mechanisms promoting bone-marrow EPC mobilization. This putative ancillary effect of DPP-IV might have a favorable impact on type 2 diabetes, a condition characterized by an increased CV risk.

This is a randomized, open-label, active-treatment-controlled, two parallel arm (2:1), intervention trial comparing DPP-IV inhibitor Vildagliptin (100 mg daily) with Glibenclamide (maximum daily dose of 10 mg). Treatment allocation and titration regimens are not blinded.

Primary end-point:Absolute and relative change in the EPC number at visit: V0 (randomization), V2 (month 4), V3 (month 8) and V4 (month 12).

Secondary end-point: Absolute and relative change in HbA1C compared to baseline.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. completion date: January 2015
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 35 Years and older

Eligibility

Inclusion Criteria:

• Age equal or above 35 years;

• Diagnosis of type 2 diabetes mellitus as defined by the American Diabetes Association , with at least one year of disease duration at the time of the screening visit;

• Blood glucose lowering treatment with Metformin alone (monotherapy) at a stable dose of at least 1.5 g/day (or maximum tolerated dose) in the 3 months prior to the screening visit;

• Insufficient metabolic control as defined by recent (last six months) HbA1c = 7% in any peripheral laboratory and confirmed at the time of the screening;

• Absence of a recent clinically-relevant progression of micro- and macro-vascular complications (see exclusion criteria);

• Written informed consent to participate to the study.

Exclusion criteria:

• Age below 35 years

• Type 1 diabetes or other causes of diabetes (pancreatectomy, gestational diabetes, etc.)

• HbA1c < 7% or = 9% at the screening visit

• Treatment with any blood glucose lowering treatment other than Metformin in the six months before screening visit

• BMI < 20 or = 40 kg/m2, or current/ past history of clinically-relevant eating disorders (including -but no limited to- nervous anorexia, bulimia, binge-eating disorders, etc.)

• Significant progression of diabetic macro-angiopathy or cardiovascular disease in the six months prior to study visit

• Significant progression of diabetic micro-angiopathy in the six months prior to study visit

• Organ failure or other severe diseases limiting life expectancy;

• Beginning, in the three months before screening visit, of any kind of drug which can modify glycemic levels (beta-blockers, diuretics…), or acute disease (acute infection, urinary tract infection…) in three months before screening visit

• History of inflammatory/infective/autoimmune chronic disease

• History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, gastric surgery, inflammatory bowel disease;

• Any clinically significant abnormality identified on physical examination, laboratory tests, ECG or vital signs at screening that in the judgment of the investigator would preclude safe completion of the study;

• Uncontrolled or inadequately controlled hypertension at screening (SBP>190 or DBP >100 mmHg)

• Ongoing pregnancy or absence of effective contraception in women with childbearing potential

• Contraindications to the maintenance of the background therapy (Metformin), including -but not limited to- chronic kidney failure or plasma creatinine concentrations > 1.5 mg/dL, severe respiratory failure, etc.;

• Contraindications to the use of a Sulfonylurea;

• Contraindications to the use of a DPP-IV Inhibitor;

• Laboratory findings, or other disease conditions, at the screening visit that might interfere with study measurements:

1. Hemoglobinopathy known to affect HbA1c assays;

2. Known chronic liver diseases, including HBV and HCV infection;

3. Liver makers (AST, ALT, ALP, GGT, bilirubin) above 2 times the upper normal limit;

4. Amylase and/or lipase above 2 times the upper normal limit;

• Chronic use of systemic and/or inhaled corticosteroids (only topical corticosteroids are allowed);

• History of low compliance, clinically-relevant psychiatric disorders or any current/ historical finding suggesting the patient as inappropriate to follow the study procedures.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• Vildagliptin
100 mg daily
• Glibenclamide
2.5 mg (total daily), progressively increased up to a maximum dose of 5 mg x 2/ day.

Locations

Country	Name	City	State
Italy	Azienda Opedaliera-Universitaria	Parma
Italy	Azienda Ospedaliera-Universitaria	Parma

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Ospedaliero-Universitaria di Parma

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Absolute and relative change in the EPC number		V0 (randomization) , V2 (month 4), V3 (month 8), V4 (month 12).
Secondary	Absolute and relative change in HbA1C compared to baseline		V0 (randomization), V2 (month4), V3 (month8), V4 (month 12).