Effect of Vildagliptin vs. Glibenclamide on Circulating Endothelial Progenitor Cell Number Type 2 Diabetes
Information source: Azienda Ospedaliero-Universitaria di Parma
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Type 2 Diabetes
Intervention: Vildagliptin (Drug); Glibenclamide (Drug)
Phase: Phase 3
Status: Not yet recruiting
Sponsored by: Azienda Ospedaliero-Universitaria di Parma Official(s) and/or principal investigator(s): Ivana Zavaroni, MD, Principal Investigator, Affiliation: Azienda Ospedaliera-Universitaria di Parma
Overall contact: Ivana Zavaroni, MD, Email: ivana.zavaroni@unipr.it
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.
Clinical Details
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 design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Absolute and relative change in the EPC number
Secondary outcome: Absolute and relative change in HbA1C compared to baseline
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 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.
Eligibility
Minimum age: 35 Years.
Maximum age: N/A.
Gender(s): Both.
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 (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.
Locations and Contacts
Ivana Zavaroni, MD, Email: ivana.zavaroni@unipr.it
Azienda Opedaliera-Universitaria, Parma 43126, Italy; Not yet recruiting Ivana Zavaroni, MD, Phone: 0521033295, Ext: 0039, Email: ivana.zavaroni@unipr.it ivana zavaroni, MD, Principal Investigator
Azienda Ospedaliera-Universitaria, Parma 43126, Italy; Not yet recruiting
Additional Information
Starting date: April 2013
Last updated: March 28, 2013
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