Type 2 DiabetesPhase 3NCT01822548
Effect of Vildagliptin vs. Glibenclamide on Circulating Endothelial Progenitor Cell Number Type 2 Diabetes
A Phase 3 study testing Vildagliptin, Glibenclamide and Metformin in people with Type 2 Diabetes, run by Azienda Ospedaliero-Universitaria di Parma at 2 sites in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 35 years and older
- Conditions the study is for
- Type 2 Diabetes
- What is being tested?
- Vildagliptin, Glibenclamide and Metformin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 2 sitesItaly
- Study dates
- Oct 2010to Jan 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 24Show fewer
- 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:
- Hemoglobinopathy known to affect HbA1c assays;
- Known chronic liver diseases, including HBV (hepatitis B virus) and HCV (hepatitis C virus) infection;
- Liver makers (aspartate transaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), Gamma-glutamyltransferase (GGT) , bilirubin) above 2 times the upper normal limit;
- 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.
Trial locations and contacts
2 sites in 1 country.
Italy2 sites
Azienda Opedaliera-Universitaria
Parma, 43126
Azienda Ospedaliera-Universitaria
Parma, 43126
About this study
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
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.
Read the 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.
- Conditions
- Type 2 Diabetes
- Being tested
- Vildagliptin, Glibenclamide, Metformin
- Keywords
- EPC, diabetes, DPP IV inhibitors
- Medical subject headings
- Diabetes Mellitus, Type 2, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VildagliptinDrug
Also called LAF237A
100 mg daily
GlibenclamideDrug
2.5 mg (total daily), progressively increased up to a maximum dose of 5 mg x 2/ day.
MetforminDrug
concomitant therapy with metformin is present in each arm (MAX dose: 2500 mg/die)
| Study group | Role | What they receive |
|---|---|---|
| Vildagliptin & metformin | Experimental | Vildagliptin 100 mg tablet and metformin (max dose=2500 mg) tablet daily oral administration Receives: Drug: Vildagliptin; Drug: Metformin |
| Glibenclamide & metformin | Active comparator | Glibenclamide maximum dose of 10 mg tablet and metformin (max dose=2500 mg) tablet daily oral administration Receives: Drug: Glibenclamide; Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Absolute Change in the Endothelial Progenitor Cell (EPC) Number
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.
Measured: V0, V2 (month 4), V4 (12 month)
Secondary outcomes (1)
Absolute Change in HbA1C Compared to Baseline
The secondary endpoint was the change from baseline values of HbA1C in the Vildagliptin vs Glibenclamide arm at 4 and 12 months
Measured: V0 (randomization), V2 (month4), V4 (month 12).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2013 (estimated)
- Study startOct 2010
- Primary completionDec 2014
- Study completionJan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Azienda Ospedaliero-Universitaria di Parma
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ivana Zavaroni, Azienda Ospedaliero-Universitaria di Parma
- Investigators
- Ivana Zavaroni, MD, Principal investigator, Azienda Ospedaliera-Universitaria di Parma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01822548
- Sponsor's protocol ID
- 2012-005399-32
- Status last verified
- Apr 2017
- First submitted
- 28 Mar 2013
- Last updated
- 2 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Dei Cas A, Spigoni V, Cito M, Aldigeri R, Ridolfi V, Marchesi E, Marina M, Derlindati E, Aloe R, Bonadonna RC, Zavaroni I. Vildagliptin, but not glibenclamide, increases circulating endothelial progenitor cell number: a 12-month randomized controlled trial in patients with type 2 diabetes. Cardiovasc Diabetol. 2017 Feb 23;16(1):27. doi: 10.1186/s12933-017-0503-0.
PubMed 28231835
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01822548
- Acronym / sponsor ID
- 2012-005399-32
- Conditions
- Type 2 Diabetes
- Keywords
- EPC, diabetes, DPP IV inhibitors
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Azienda Ospedaliero-Universitaria di ParmaUniversity, hospital or other
- Study start
- Oct 2010
- Primary completion
- Dec 2014 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 2 Apr 2013 (estimated)
- Results
- Posted 2 Aug 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vildagliptin & metformin | Experimental | Drug: Vildagliptin, Drug: MetforminVildagliptin 100 mg tablet and metformin (max dose=2500 mg) tablet daily oral administration |
| Glibenclamide & metformin | Active comparator | Drug: Glibenclamide, Drug: MetforminGlibenclamide maximum dose of 10 mg tablet and metformin (max dose=2500 mg) tablet daily oral administration |
Who may qualify
- Ages
- 35 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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);
Key exclusion criteria (24 listed)
- 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.)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VildagliptinAlso: LAF237A100 mg daily | Drug | Vildagliptin & metformin |
| Glibenclamide2.5 mg (total daily), progressively increased up to a maximum dose of 5 mg x 2/ day. | Drug | Glibenclamide & metformin |
| Metforminconcomitant therapy with metformin is present in each arm (MAX dose: 2500 mg/die) | Drug | Glibenclamide & metformin, Vildagliptin & metformin |
Primary outcome
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.
1 secondary outcome
Absolute Change in HbA1C Compared to Baseline
Time frame: V0 (randomization), V2 (month4), V4 (month 12).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28231835Dei Cas A, Spigoni V, Cito M, Aldigeri R, Ridolfi V, Marchesi E, Marina M, Derlindati E, Aloe R, Bonadonna RC, Zavaroni I. Vildagliptin, but not glibenclamide, increases circulating endothelial progenitor cell number: a 12-month randomized controlled trial in patients with type 2 diabetes. Cardiovasc Diabetol. 2017 Feb 23;16(1):27. doi: 10.1186/s12933-017-0503-0.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ivana Zavaroni, MD principal investigator
Azienda Ospedaliera-Universitaria di Parma
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Vildagliptin, Glibenclamide and Metformin in people with Type 2 Diabetes, run by Azienda Ospedaliero-Universitaria di Parma at 2 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Aug 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Absolute Change in the Endothelial Progenitor Cell (EPC) Number (time frame: V0, V2 (month 4), V4 (12 month)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01822548, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2017.