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

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ClinicalTrials.gov Identifier: NCT01822548
Recruitment Status : Completed
First Posted : April 2, 2013
Results First Posted : August 2, 2017
Last Update Posted : August 2, 2017
Sponsor:
Information provided by (Responsible Party):
Ivana Zavaroni, Azienda Ospedaliero-Universitaria di Parma

Brief Summary:
The purpose of this study is to evaluate the effect of Dipeptidyl peptidase (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.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Drug: Vildagliptin Drug: Glibenclamide Drug: Metformin Phase 3

Detailed 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 DPP-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 change in the EPC number at visit: V0 (randomization), V2 (month 4), V3 (month 8) and V4 (month 12).

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


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 64 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : October 2010
Actual Primary Completion Date : December 2014
Actual Study Completion Date : January 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Vildagliptin & metformin
Vildagliptin 100 mg tablet and metformin (max dose=2500 mg) tablet daily oral administration
Drug: Vildagliptin
100 mg daily
Other Name: LAF237A

Drug: Metformin
concomitant therapy with metformin is present in each arm (MAX dose: 2500 mg/die)

Active Comparator: Glibenclamide & metformin
Glibenclamide maximum dose of 10 mg tablet and metformin (max dose=2500 mg) tablet daily oral administration
Drug: Glibenclamide
2.5 mg (total daily), progressively increased up to a maximum dose of 5 mg x 2/ day.

Drug: Metformin
concomitant therapy with metformin is present in each arm (MAX dose: 2500 mg/die)




Primary Outcome Measures :
  1. Absolute Change in the Endothelial Progenitor Cell (EPC) Number [ Time Frame: V0, V2 (month 4), V4 (12 month) ]
    The study primary endpoint was the change from baseline values of the EPC number in the Vildagliptin vs Glibenclamide arm at 4 and 12 months.


Secondary Outcome Measures :
  1. Absolute Change in HbA1C Compared to Baseline [ Time Frame: V0 (randomization), V2 (month4), V4 (month 12). ]
    The secondary endpoint was the change from baseline values of HbA1C in the Vildagliptin vs Glibenclamide arm at 4 and 12 months



Information from the National Library of Medicine

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Ages Eligible for Study:   35 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 (Systolic Blood Pressure (SBP)>190 or Diastolic Blood Pressure (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 (hepatitis B virus) and HCV (hepatitis C virus) infection;
    3. Liver makers (aspartate transaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), Gamma-glutamyltransferase (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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01822548


Locations
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Italy
Azienda Opedaliera-Universitaria
Parma, Italy, 43126
Azienda Ospedaliera-Universitaria
Parma, Italy, 43126
Sponsors and Collaborators
Azienda Ospedaliero-Universitaria di Parma
Investigators
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Principal Investigator: Ivana Zavaroni, MD Azienda Ospedaliera-Universitaria di Parma

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Ivana Zavaroni, Prof., Azienda Ospedaliero-Universitaria di Parma
ClinicalTrials.gov Identifier: NCT01822548     History of Changes
Other Study ID Numbers: 2012-005399-32
First Posted: April 2, 2013    Key Record Dates
Results First Posted: August 2, 2017
Last Update Posted: August 2, 2017
Last Verified: April 2017
Keywords provided by Ivana Zavaroni, Azienda Ospedaliero-Universitaria di Parma:
EPC
diabetes
DPP IV inhibitors
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Metformin
Vildagliptin
Glyburide
Hypoglycemic Agents
Physiological Effects of Drugs
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action