Diabetes MellitusPhase 4SPLENDORNCT00770835
Efficacy and Safety of Pioglitazone in Treating Subjects With Vascular Complications Associated With Type 2 Diabetes Mellitus.
A Phase 4 study testing Pioglitazone and Metformin and Glibenclamide and Metformin in people with Diabetes Mellitus, run by Takeda at 2 sites in Italy.
Trial summary
The purpose of this study is to determine the efficacy of pioglitazone compared to glibenclamide, once daily (QD), taken together with metformin and lifestyle modification in type 2 diabetic subjects with cardiovascular disease. Read more about this study
- Who is it for?
- Ages 40 to 70 years
- Conditions the study is for
- Diabetes Mellitus
- What is being tested?
- Pioglitazone and Metformin and Glibenclamide and Metformin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 2 sitesItaly
- Study dates
- Mar 2009to May 2011
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 40 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Females must be non-pregnant, non-lactating and post-menopausal.
- A glycosylated hemoglobin level greater than 7.5% and less than 10%.
- Has an age of onset of Type 2 Diabetes greater than 35 years of age.
- Is on metformin monotherapy up to the maximum tolerated daily dose.
- Has a normal or only slightly impaired renal function (a modification of diet in renal disease estimated glomerular filtration rate greater than 60 ml/min/1.73m2.
- Antihypertensives, statins and any other hypolipidemic medications have been initiated at least three months prior to enrollment; no dose modifications are allowed during the study.
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- Has one or more cardiovascular comorbidities as follows:
- stable angina pectoris
- previous (greater than three months) transient ischemic attack, cerebrovascular accident or carotid atherosclerosis as assessed by bilateral carotid artery ultrasonography
- peripheral vascular complications documented by a history of claudication or rest pain, ultrasonography or angiography.
- and/or two or more of the following major cardiovascular risk factors:
- hypertension (blood pressure >130/80 mmHg or treatment)
- dyslipidemia (low-density lipoprotein-cholesterol >100 mg/dl or treatment and/or high-density lipoprotein-cholesterol <40 mg/dl in men and <45 mg/dl in women or treatment)
- smoking (>10 cigarettes/day)
Who cannot join
- Has Type 1 Diabetes.
- Is on insulin therapy.
- Is severely obese defined as a body mass index greater than or equal to 40mg/m2
- Has diabetic retinopathy.
- Has evidence of hepatic dysfunction including liver transaminase greater than three times the upper limit of normal.
- Is unable to remain on a stable dose of the following class of medications 30 days prior to randomization and throughout the six months of the study:
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- antihypertensives
- statins
- other hypolipidemic and antiplatelet drugs
- Has a history of alcohol or other drug abuse.
- Has had a new diagnosis of cancer or recurrent cancer within five years of screening.
- Has a need for chronic (greater than two weeks) immunosuppressive therapy.
- Has had heart failure based on the New York Heart Association Functional Class I through IV.
- Is required to take or intends to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:
- Other antidiabetic drugs (except metformin)
- Fibrates
- Rifampicin
- Glibenclamide interacting drugs, including nonsteroidal anti-inflammatory agents
- Other drugs that are highly protein bound, including:
- sulphonamides
- chloramphenicol
- probenecid
- monoamine oxidase inhibitors
- fluoroquinolones antibiotics
- oral miconazole
- Has participated in another clinical study within the past three months.
Trial locations and contacts
2 sites in 1 country.
About this study
Official title: Effects of Pioglitazone on Endothelial Progenitor Cells in Type 2 Diabetic Patients With Vascular Complications - The SPLENDOR Study.
The purpose of this study is to determine the efficacy of pioglitazone compared to glibenclamide, once daily (QD), taken together with metformin and lifestyle modification in type 2 diabetic subjects with cardiovascular disease.
Read the detailed description
Diabetes is one of the most common chronic diseases worldwide, affecting nearly 200 million people, almost all suffering from Type 2 Diabetes. It is the fourth leading cause of death in developed countries due to the negative impact of the disease on the cardiovascular system. Treatment, aimed to the reduction of this intrinsic cardiovascular risk, is based on tight control of glucose and all coexisting metabolic abnormalities as well as of biomarkers of inflammation and atherogenesis.
Macrovascular complications account for the vast majority of morbidity and mortality in diabetic patients, and there is growing evidence that pathophysiologic mechanisms other than hyperglycemia are responsible. The condition of the vascular endothelium in particular has been shown to effect the health and disease of the cardiovascular system.
The number and function of endothelial progenitor cells correlate inversely with cardiovascular risk factors and may be a surrogate biologic marker for vascular function and cumulative cardiovascular risk.
Pioglitazone is an orally active thiazolidinedione derivative. It is a ligand for peroxisome proliferator-activated receptor-gamma activation that alters transcription of various genes regulating carbohydrate and lipid metabolism.
- Conditions
- Diabetes Mellitus
- Being tested
- Pioglitazone and Metformin, Glibenclamide and Metformin
- Keywords
- Glucose Metabolism Disorder, Dysmetabolic Syndrome, Type II Diabetes, Diabetes Mellitus, Lipoatrophic, Dyslipidemia, Drug Therapy
- Medical subject headings
- Diabetes Mellitus, Glucose Metabolism Disorders, Diabetes Mellitus, Type 2, Diabetes Mellitus, Lipoatrophic, Dyslipidemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pioglitazone and MetforminDrug
Also called ACTOS®, AD-4833
Pioglitazone 30 mg, tablets, orally, once daily, metformin stable dose and lifestyle modification for up to 24 weeks.
Glibenclamide and MetforminDrug
Also called Diabeta, Glynase, Micronase, Daonil
Glibenclamide 10 mg, tablets, orally, once daily and metformin stable dose and lifestyle modification for up to 24 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Pioglitazone and Metformin QD | Experimental | (along with lifestyle modification) Receives: Drug: Pioglitazone and Metformin |
| Glibenclamide and Metformin QD | Active comparator | (along with lifestyle modification) Receives: Drug: Glibenclamide and Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Increase from Baseline in the number of Endothelial Progenitor Cells (CD34+KDR+).
Measured: Baseline and Final Visit.
Secondary outcomes (11)
Change from Baseline in Circulating Progenitor Cells Integrated Markers of cardiovascular risk (CD34+).
Measured: Baseline and Weeks 12 and 24.
Change from Baseline in Flow Mediated Dilation Integrated Markers of cardiovascular risk.
Measured: Baseline and Final Visit.
Modulation of Endothelial Progenitor Cell recruitment (vascular endothelial growth factor, erythropoietin and stromal cell-derived factor-1).
Measured: Weeks: 4, 12 and 24.
Measure of Glucose Control (glycosylated hemoglobin and fasting plasma glucose).
Measured: Weeks: 4, 12 and 24.
Measure of Lipid Parameters (total lipids, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein B and apolipoprotein A1).
Measured: Weeks: 4, 12 and 24.
Change from Baseline in lipid parameters (free fatty acids and oxidized low-density lipoprotein).
Measured: Baseline and Weeks 12 and 24.
Change from Baseline in insulin sensitivity (insulin indexes by 2 hour oral glucose tolerance test with glucose, insulin and C-peptide estimation).
Measured: Baseline and Final Visit.
Change from Baseline in Inflammation Markers (high-sensitivity C-reactive protein, IL-6, vascular adhesion molecules (E-selectin, vascular cell adhesion molecule-1), monocyte chemotactic protein-1 and tumor necrosis factor-alpha).
Measured: Baseline and Weeks 12 and 24.
Change from Baseline in Adipokines (adiponectin).
Measured: Baseline and Weeks 12 and 24.
Change from Baseline in Oxidative Stress (maleic dialdehyde, ferric reducing antioxidant power and lipid hydroperoxide.
Measured: Baseline and Weeks 12 and 24.
Urinary albumin excretion.
Measured: Weeks: 12 and 24.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2008 (estimated)
- Study startMar 2009
- Primary completionMay 2011
- Study completionMay 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by TakedaThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Medical Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00770835
- Sponsor's protocol ID
- IT-PIO-109
- Other IDs
- 2007-003077-44, U1111-1114-3045
- Acronym
- SPLENDOR
- Status last verified
- Jul 2011
- First submitted
- 8 Oct 2008
- Last updated
- 12 Jul 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Pioglitazone on Endothelial Progenitor Cells in Type 2 Diabetic Patients With Vascular Complications - The SPLENDOR Study.
- ClinicalTrials.gov ID
- NCT00770835
- Acronym / sponsor ID
- SPLENDOR / IT-PIO-109
- Conditions
- Diabetes Mellitus
- Keywords
- Glucose Metabolism Disorder, Dysmetabolic Syndrome, Type II Diabetes, Diabetes Mellitus, Lipoatrophic, Dyslipidemia, Drug Therapy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- Mar 2009
- Primary completion
- May 2011 (actual)
- Study completion
- May 2011 (actual)
- First posted
- 10 Oct 2008 (estimated)
- Results
- Not posted in the source record
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 determine the efficacy of pioglitazone compared to glibenclamide, once daily (QD), taken together with metformin and lifestyle modification in type 2 diabetic subjects with cardiovascular disease.
Detailed description
Diabetes is one of the most common chronic diseases worldwide, affecting nearly 200 million people, almost all suffering from Type 2 Diabetes. It is the fourth leading cause of death in developed countries due to the negative impact of the disease on the cardiovascular system. Treatment, aimed to the reduction of this intrinsic cardiovascular risk, is based on tight control of glucose and all coexisting metabolic abnormalities as well as of biomarkers of inflammation and atherogenesis.
Macrovascular complications account for the vast majority of morbidity and mortality in diabetic patients, and there is growing evidence that pathophysiologic mechanisms other than hyperglycemia are responsible. The condition of the vascular endothelium in particular has been shown to effect the health and disease of the cardiovascular system.
The number and function of endothelial progenitor cells correlate inversely with cardiovascular risk factors and may be a surrogate biologic marker for vascular function and cumulative cardiovascular risk.
Pioglitazone is an orally active thiazolidinedione derivative. It is a ligand for peroxisome proliferator-activated receptor-gamma activation that alters transcription of various genes regulating carbohydrate and lipid metabolism.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pioglitazone and Metformin QD | Experimental | Drug: Pioglitazone and Metformin(along with lifestyle modification) |
| Glibenclamide and Metformin QD | Active comparator | Drug: Glibenclamide and Metformin(along with lifestyle modification) |
Who may qualify
- Ages
- 40 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Females must be non-pregnant, non-lactating and post-menopausal.
- A glycosylated hemoglobin level greater than 7.5% and less than 10%.
- Has an age of onset of Type 2 Diabetes greater than 35 years of age.
- Is on metformin monotherapy up to the maximum tolerated daily dose.
- Has a normal or only slightly impaired renal function (a modification of diet in renal disease estimated glomerular filtration rate greater than 60 ml/min/1.73m2.
Key exclusion criteria (26 listed)
- Has Type 1 Diabetes.
- Is on insulin therapy.
- Is severely obese defined as a body mass index greater than or equal to 40mg/m2
- Has diabetic retinopathy.
- Has evidence of hepatic dysfunction including liver transaminase greater than three times the upper limit of normal.
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 |
|---|---|---|
| Pioglitazone and MetforminAlso: ACTOS®, AD-4833Pioglitazone 30 mg, tablets, orally, once daily, metformin stable dose and lifestyle modification for up to 24 weeks. | Drug | Pioglitazone and Metformin QD |
| Glibenclamide and MetforminAlso: Diabeta, Glynase, Micronase, DaonilGlibenclamide 10 mg, tablets, orally, once daily and metformin stable dose and lifestyle modification for up to 24 weeks. | Drug | Glibenclamide and Metformin QD |
Primary outcome
Increase from Baseline in the number of Endothelial Progenitor Cells (CD34+KDR+).
Time frame: Baseline and Final Visit.
11 secondary outcomes
Change from Baseline in Circulating Progenitor Cells Integrated Markers of cardiovascular risk (CD34+).
Time frame: Baseline and Weeks 12 and 24.
Change from Baseline in Flow Mediated Dilation Integrated Markers of cardiovascular risk.
Time frame: Baseline and Final Visit.
Modulation of Endothelial Progenitor Cell recruitment (vascular endothelial growth factor, erythropoietin and stromal cell-derived factor-1).
Time frame: Weeks: 4, 12 and 24.
Measure of Glucose Control (glycosylated hemoglobin and fasting plasma glucose).
Time frame: Weeks: 4, 12 and 24.
Measure of Lipid Parameters (total lipids, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein B and apolipoprotein A1).
Time frame: Weeks: 4, 12 and 24.
Change from Baseline in lipid parameters (free fatty acids and oxidized low-density lipoprotein).
Time frame: Baseline and Weeks 12 and 24.
Change from Baseline in insulin sensitivity (insulin indexes by 2 hour oral glucose tolerance test with glucose, insulin and C-peptide estimation).
Time frame: Baseline and Final Visit.
Change from Baseline in Inflammation Markers (high-sensitivity C-reactive protein, IL-6, vascular adhesion molecules (E-selectin, vascular cell adhesion molecule-1), monocyte chemotactic protein-1 and tumor necrosis factor-alpha).
Time frame: Baseline and Weeks 12 and 24.
Change from Baseline in Adipokines (adiponectin).
Time frame: Baseline and Weeks 12 and 24.
Change from Baseline in Oxidative Stress (maleic dialdehyde, ferric reducing antioxidant power and lipid hydroperoxide.
Time frame: Baseline and Weeks 12 and 24.
Urinary albumin excretion.
Time frame: Weeks: 12 and 24.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2011.
- ACTOS® Package InsertLink provided by the sponsor.
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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.
Medical Director study director
Takeda
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Pioglitazone and Metformin and Glibenclamide and Metformin in people with Diabetes Mellitus, run by Takeda 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 14 inclusion and 26 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 12 Jul 2011. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Increase from Baseline in the number of Endothelial Progenitor Cells (CD34+KDR+). (time frame: Baseline and Final Visit.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Jul 2011.