Type 2 DiabetesPhase 4ADELANTENCT01593137
A Long-term Trial to Compare the Effects of Liraglutide and Sulphonylurea (Glimepiride) Both in Combination With Metformin on Clinical, Endothelial and Image Markers of Cardiovascular Risk in Patients With Type 2 Diabetes
A Phase 4 study testing Liraglutide + metformin and Glimepiride + metformin in people with Type 2 Diabetes, run by Fundación Fernández-Cruz at 1 site in Spain.
Trial summary
The process of atherosclerosis is multifactorial and involves many mechanisms. The majority of published works have identified endothelial dysfunction as the first step in a cascade of events that culminates in plaque formation. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Type 2 Diabetes
- What is being tested?
- Liraglutide + metformin and Glimepiride + metformin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteSpain
- Study dates
- May 2012to Dec 2014
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Informed written consent obtained before any trial-related activities (trial-related activities are any procedures that would not have been performed during normal management of the subject).
- Male or female patients between 18 and 75 years old;
- Subjects diagnosed with type 2 diabetes for more than 1 year
- Insulin naïve subjects (Allowed are: Previous short term insulin treatment < 28 days in total; Treatment during hospitalisation or during gestational diabetes is allowed for periods < 14 days in total)
- Subjects previously treated with metformin at a minimum dose of 1500 mg/day
- HbA1c from 7% to 9%
- Adherence to injection therapy
Who cannot join
- Type 1 diabetic patients;
- Use of a GLP-1 receptor agonist (exenatide, liraglutide or other), pramlintide, thiazolidinediones or any DPP-4 inhibitor within the 3 months prior to screening;
- Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods (or their partners). Adequate contraceptive measures are considered the use of hormonal based contraceptives in combination with a barrier contraception,
- Patients with a clinical history of serious cardiovascular events in the last 3 months (myocardial infarction, unstable angina, cerebral infarction, TIA, peripheral arteriopathic event);
- Suspected or confirmed acute pancreatitis;
- Personal history of medullary thyroid carcinoma;
Show all 17Show fewer
- Patients with congestive heart failure (NYHA I-IV);
- Moderate or severe renal failure (creatinine clearance < 60 ml/min);
- Patients with hepatic failure. This is AST or ALT > 3 times the upper limit of normal, history of cirrhosis or hepatitis;
- Patients with cancer in the last 10 years;
- Patients with terminal diseases;
- Patients unlikely to comply with trial procedures;
- Known psychiatric disease which may interfere with study procedure;
- Any other pathology which may interfere with the study results at the investigator's discretion;
- Known or suspected contraindications to or history of hypersensitivity to the trial product or related products;
- Previous participation in this trial i.e. randomised;
- The receipt of any investigational product within 30 days.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Long-term, Randomized, Open-labeled, Parallel-group Trial to Compare the Effects of Liraglutide and Sulphonylurea (Glimepiride) Both in Combination With Metformin on Clinical, Endothelial and Image Markers of Cardiovascular Risk in Patients With Type 2 Diabetes
The process of atherosclerosis is multifactorial and involves many mechanisms. The majority of published works have identified endothelial dysfunction as the first step in a cascade of events that culminates in plaque formation. Among the various mechanisms that occur following the attack on the vessel wall, it is thought that stem cells in the form of endothelial progenitor cells (EPCs) are the endothelial protection mechanism.
Factors identified as cardiovascular risk factors, or rather those conditions which suppose a threat to the vessel wall, should therefore be associated with low levels of EPCs. To date this link has been shown in hypertension, diabetes, hyperlipidaemia, and smoking. Furthermore, the lack of wall protection in situations of low levels of EPCs is clearly a biomarker of cardiovascular morbidity and mortality.
Read more
On the other hand, the correction of a risk factor allows recuperation of EPCs and is therefore showing itself to be a promising tool for measuring therapeutic efficacy.
The tools for correcting EPC levels are not clearly defined. The effect of statins on levels of EPC has been shown, and the low levels of EPCs in diabetes seem to be susceptible to treatment with statins.
The role of glucagon-like peptide (GLP-1) is slowly being elucidated but the actual mechanism of its potential endothelial protection is unknown, and its effect on EPCs has not been studied.
Liraglutide, a long-acting GLP-1 analogue, could also be an interesting option for long-term vessel wall protection, but to date its ability to correct cardiovascular biomarkers such as EPCs has not been studied.
- Conditions
- Type 2 Diabetes
- Being tested
- Liraglutide + metformin, Glimepiride + metformin
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Liraglutide + metforminDrug
Liraglutide 1.8 mg/day + metformin >1500mg/day. Liraglutide will be administered once daily by subcutaneous injection, either in the abdomen, thigh or upper arm.
Patients will continue on metformin therapy as they were prescribed before enrolment.
Glimepiride + metforminDrug
Glimepiride 4 mg/day + metformin >1500 mg/day. Tablets should be swallowed whole with some liquid before or during a substantial breakfast or, if none is taken, shortly before or during the first main meal.
Patients will continue on metformin therapy as they were prescribed before enrolment.
| Study group | Role | What they receive |
|---|---|---|
| Liraglutide + metformin | Experimental | Not described Receives: Drug: Liraglutide + metformin |
| glimepiride + metformin | Active comparator | Not described Receives: Drug: Glimepiride + metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
assess the effect of treatment with liraglutide compared to glimepiride, as add-on to metformin, for one year on circulating levels of EPCs in patients with type 2 diabetes poorly controlled.
Measured: 1 year
Secondary outcomes (3)
assess the efficacy of liraglutide compared to glimepiride, as add-on to metformin, with regards to other surrogate biomarkers of cardiovascular risk: IMT, Central BP, CD40L, hsCRP, Lp-PLA2, BNP.
Measured: 1 year
Relationship between EPC levels and all these biomarkers in patients treated with liraglutide compared to those treated with glimepiride.
Measured: 1 year
Safety parameters of glycaemic control: HbA1c, FPG
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2012 (estimated)
- Study startMay 2012
- Primary completionDec 2013 (estimated)
- Study completionDec 2014 (estimated)
Why it stopped: Lack of patients with the criteria established in the protocol.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 4
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundación Fernández-Cruz
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alfonso Calle, MD, Principal investigator, Hospital Clínico San Carlos, Department of Endocrinology, Metabolism and Nutrition, Spain
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01593137
- Sponsor's protocol ID
- FFC-0001
- Other IDs
- 2012-000311-87
- Acronym
- ADELANTE
- Status last verified
- Jul 2013
- First submitted
- 3 May 2012
- Last updated
- 2 Jul 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Long-term, Randomized, Open-labeled, Parallel-group Trial to Compare the Effects of Liraglutide and Sulphonylurea (Glimepiride) Both in Combination With Metformin on Clinical, Endothelial and Image Markers of Cardiovascular Risk in Patients With Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT01593137
- Acronym / sponsor ID
- ADELANTE / FFC-0001
- Conditions
- Type 2 Diabetes
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Lack of patients with the criteria established in the protocol.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Fundación Fernández-CruzUniversity, hospital or other
- Study start
- May 2012
- Primary completion
- Dec 2013 (estimated)
- Study completion
- Dec 2014 (estimated)
- First posted
- 7 May 2012 (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 process of atherosclerosis is multifactorial and involves many mechanisms. The majority of published works have identified endothelial dysfunction as the first step in a cascade of events that culminates in plaque formation. Among the various mechanisms that occur following the attack on the vessel wall, it is thought that stem cells in the form of endothelial progenitor cells (EPCs) are the endothelial protection mechanism.
Factors identified as cardiovascular risk factors, or rather those conditions which suppose a threat to the vessel wall, should therefore be associated with low levels of EPCs. To date this link has been shown in hypertension, diabetes, hyperlipidaemia, and smoking. Furthermore, the lack of wall protection in situations of low levels of EPCs is clearly a biomarker of cardiovascular morbidity and mortality.
On the other hand, the correction of a risk factor allows recuperation of EPCs and is therefore showing itself to be a promising tool for measuring therapeutic efficacy.
The tools for correcting EPC levels are not clearly defined. The effect of statins on levels of EPC has been shown, and the low levels of EPCs in diabetes seem to be susceptible to treatment with statins.
The role of glucagon-like peptide (GLP-1) is slowly being elucidated but the actual mechanism of its potential endothelial protection is unknown, and its effect on EPCs has not been studied.
Liraglutide, a long-acting GLP-1 analogue, could also be an interesting option for long-term vessel wall protection, but to date its ability to correct cardiovascular biomarkers such as EPCs has not been studied.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Liraglutide + metformin | Experimental | Drug: Liraglutide + metformin |
| glimepiride + metformin | Active comparator | Drug: Glimepiride + metformin |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Informed written consent obtained before any trial-related activities (trial-related activities are any procedures that would not have been performed during normal management of the subject).
- Male or female patients between 18 and 75 years old;
- Subjects diagnosed with type 2 diabetes for more than 1 year
- Insulin naïve subjects (Allowed are: Previous short term insulin treatment < 28 days in total; Treatment during hospitalisation or during gestational diabetes is allowed for periods < 14 days in total)
- Subjects previously treated with metformin at a minimum dose of 1500 mg/day
Key exclusion criteria (17 listed)
- Type 1 diabetic patients;
- Use of a GLP-1 receptor agonist (exenatide, liraglutide or other), pramlintide, thiazolidinediones or any DPP-4 inhibitor within the 3 months prior to screening;
- Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods (or their partners). Adequate contraceptive measures are considered the use of hormonal based contraceptives in combination with a barrier contraception,
- Patients with a clinical history of serious cardiovascular events in the last 3 months (myocardial infarction, unstable angina, cerebral infarction, TIA, peripheral arteriopathic event);
- Suspected or confirmed acute pancreatitis;
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 |
|---|---|---|
| Liraglutide + metforminLiraglutide 1.8 mg/day + metformin >1500mg/day. Liraglutide will be administered once daily by subcutaneous injection, either in the abdomen, thigh or upper arm. Patients will continue on metformin therapy as they were prescribed before enrolment. | Drug | Liraglutide + metformin |
| Glimepiride + metforminGlimepiride 4 mg/day + metformin >1500 mg/day. Tablets should be swallowed whole with some liquid before or during a substantial breakfast or, if none is taken, shortly before or during the first main meal. Patients will continue on metformin therapy as they were prescribed before enrolment. | Drug | glimepiride + metformin |
Primary outcome
assess the effect of treatment with liraglutide compared to glimepiride, as add-on to metformin, for one year on circulating levels of EPCs in patients with type 2 diabetes poorly controlled.
Time frame: 1 year
3 secondary outcomes
assess the efficacy of liraglutide compared to glimepiride, as add-on to metformin, with regards to other surrogate biomarkers of cardiovascular risk: IMT, Central BP, CD40L, hsCRP, Lp-PLA2, BNP.
Time frame: 1 year
Relationship between EPC levels and all these biomarkers in patients treated with liraglutide compared to those treated with glimepiride.
Time frame: 1 year
Safety parameters of glycaemic control: HbA1c, FPG
Time frame: 1 year
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2013.
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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.
Alfonso Calle, MD principal investigator
Hospital Clínico San Carlos, Department of Endocrinology, Metabolism and Nutrition, Spain
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Liraglutide + metformin and Glimepiride + metformin in people with Type 2 Diabetes, run by Fundación Fernández-Cruz at 1 site in Spain.
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 7 inclusion and 17 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: withdrawn, as of the sponsor's last update on 2 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. 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 was withdrawn before enrolling participants, so there are no results.
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?
assess the effect of treatment with liraglutide compared to glimepiride, as add-on to metformin, for one year on circulating levels of EPCs in patients with type 2 diabetes poorly controlled. (time frame: 1 year). 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 2 Jul 2013.