Diabetes Mellitus, Type 2NCT01206712
Beta Cell Relieving and Cardiovascular Protective Effects of LANTUS Treatment in Type 2 Diabetes Patients
An observational study of Diabetes Mellitus, Type 2, run by ikfe-CRO GmbH at 1 site in Germany.
Trial summary
The purpose of this phase IV clinical trial is to investigate the effect of Insulin glargine + metformin treatment vs. sulfonylurea + metformin treatment vs. DPP-4 + metformin treatment vs. healthy volunteers on ß-cell function after the uptake of a standardized meal. Read more about this study
- Who is it for?
- Ages 40 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus, Type 2
- How many people
- 106 participants
- Where
- 1 siteGermany
- Study dates
- Nov 2009to Jul 2010
- Phase
- Observational
- 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 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: * Group 1 (n=20): Healthy subjects * Group 2 (n=20): T2DM patients treated with continuous SU + MET therapy as individually prescriped by the primary care physicians * Group 3 (n=20): T2DM patients treated with continuous LANTUS + MET therapy as individually prescriped by the primary care physicians * Group 4 (n=20): T2DM patients treated with continuous DPP-4 + MET therapy as individually prescriped by the primary care physicians
Who may be able to join
- Inclusion criteria - applicable for T2DM group only:
- 1.1. Type 2 diabetes mellitus 1.2. Duration of T2DM between 3 and 15 years inclusively 1.3. HbA1c up to 7.5% inclusively 1.4. Treated with LANTUS+MET (Group LANTUS+MET) or SU+MET (Group SU+MET) or DPP-4+MET (Group DPP-4+MET) respectively during the past 6 months before entering the study 1.5. Treated on a stable antidiabetic dosage during the past 3 months before entering the study
- Inclusion criteria - applicable for healthy subject only:
- 2.1. Fasting blood glucose £ 100 mg/dl (5.6 mmol/l) 2.2. Oral Glucose Tolerance Test (OGTT) revealed no IGT or DM
- Age of 40-75 years inclusively
- BMI between 20 and 35 kg/m2 inclusively
- Patient informed consent
Who cannot join
- Exclusion criteria - applicable for T2DM group only:
- 1.1. Type 1 diabetes mellitus 1.2. Treatment with any other insulin than LANTUS during the past 6 months in Group LANTUS+MET or with any kind of insulin during the past 3 months in Group SU+MET or Group DPP-4+MET before entering the study 1.3. Treatment with any kind of OAD except MET during the past 6 months in Group LANTUS+MET or with any kind of OAD except MET+SU during the past 3 months in Group SU+MET or with any kind of OAD except DPP-4+SU during the past 3 months in Group DPP-4+MET before entering the study 1.4. Major micro- or macro vascular complications as judged by the investigator
- Exclusion criteria - applicable for healthy subject only:
- 2.1. Type 1 or type 2 diabetes mellitus (checked by oGTT) 2.2. Impaired Glucose Tolerance (IGT, checked by oGTT) 2.3. Impaired Fasting Glucose (IFG, checked by oGTT)
- History of drug or alcohol abuse within the last five years prior to screening
- History of severe or multiple allergies
Show all 13Show fewer
- Treatment with any other investigational drug within 3 months prior to screening
- Progressive fatal disease
- Known psychiatric illness
- History of significant cardiovascular, respiratory, gastrointestinal, hepatic (ALAT and/or ASAT > 3 times the normal reference range), renal (creatinine > 1.1 mg/dl in women and > 1.5 mg/dl in men), neurological, psychiatric and/or haematological disease as judged by the investigator
- Pregnancy or breast feeding
- Sexually active women of childbearing potential not consistently and correctly practicing birth control by implants, injectables, combined oral contraceptives, hormonal intrauterine devices (IUDs), sexual abstinence or vasectomised partner
- Lack of compliance or other similar reason, that according to investigator, precludes satisfactory participation in the study
Trial locations and contacts
1 site in 1 country.
Germany1 site
IKFE Institute for Clinical Research and Development
Mainz, 55116
About this study
Official title: Beta Cell Relieving and Cardiovascular Protective Effects of LANTUS Treatment in Type 2 Diabetes Patients - Investigation on Postprandial Excursions of Proinsulin and PAI-1 Levels
The purpose of this phase IV clinical trial is to investigate the effect of Insulin glargine + metformin treatment vs. sulfonylurea + metformin treatment vs. DPP-4 + metformin treatment vs. healthy volunteers on ß-cell function after the uptake of a standardized meal.
Read the detailed description
Type 2 diabetes mellitus is a progressive disease characterised by a steady loss of beta cell function and an increase in the proinsulin/insulin ratio. During the recent years intact proinsulin has been the topic of interest in numerous preclinical and clinical studies in patients with type 2 diabetes mellitus. Intact proinsulin was confirmed as a marker of functional beta cell failure and as a predictor of increased beta cell loss due to apoptosis and/or diminished neogenesis.
A number of population based studies showed that intact proinsulin is a strong predictor of coronary heart disease in diabetic, and in non-diabetic patients. In a clinical trial investigating human proinsulin as a therapeutic approach for the treatment of diabetes mellitus an eight fold increase in CVD was found during treatment with human proinsulin compared to human regular insulin, indicating a thrombo-embolic potential of intact proinsulin. In a recent investigation an association could be confirmed between increased proinsulin plasma concentrations and the severity of angiographical characterised CHD.
Even the exact mechanism how proinsulin is involved in the pathogenesis of atherosclerosis is not completely recognized, it was already shown that PAI-1 activity increases after proinsulin administration in vitro, and there is increasing evidence that the atherogenic effects of proinsulin might be linked to increasing plasminogen activator inhibitor-1 (PAI-1) levels with subsequent inhibition of fibrinolysis and an augmented thrombogenic potency.
Treatment with sulfonylurea increases intact proinsulin secretion, and in a couple of studies, sulfonylurea treatment was found to be associated with an increased cardiovascular risk. In contrast, several studies have shown that after the introduction of insulin treatment in type 2 diabetic patients intact proinsulin levels and plasma PAI 1 levels decline, indicating not only beta cell protection, but also antiatherogenic properties of insulin. In a recent study, we have shown that treatment with basal insulin in combination with metformin effectively reduces intact proinsulin levels, and that insulin glargine is superior to NPH insulin in controlling postprandial release of intact proinsulin over an entire day.
Recently a new therapeutic concept using DPP IV inhibitors in combination with metformin has been introduced in the treatment of type 2 diabetic patients. There is some evidence that, in the beta cell, DPP IV Inhibitors might improve the conversion of intact Proinsulin into Insulin and C-peptide and thereby reduce circulating intact proinsulin levels. Since the number of type 2 diabetic patients treated with DPP-IV inhibitors is steadily increasing, there is a need to generate more data on the postprandial release of intact proinsulin in patients treated with DPP-IV inhibitors compared to Insulin or sulfonylurea treatment.
The rationale of the study is to investigate the effect of glargine and metformin treatment compared to sulfonylurea and metformin treatment and compared to DPP-4 inhibitor and metformin treatment on postprandial intact proinsulin release and postprandial PAI-1 levels. Accompanying a comparison of postprandial intact proinsulin release and the time course of postprandial PAI-levels in between all three antidiabetic treatment groups and a non-diabetic control group will be performed as well.
- Conditions
- Diabetes Mellitus, Type 2
- Keywords
- Diabetes Mellitus Type 2, insulin glargine, 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.
| Study group | Role | What they receive |
|---|---|---|
| T2DM patients treated with LANTUS + MET | T2DM patients treated with LANTUS + Metformin(MET) in their routine antidiabetic therapy. These patients do not receive any study specific medication. | |
| T2DM patients treated with SU + MET | T2DM patients treated with Sulfonylurea (SU) + Metformin(MET)in their routine antidiabetic therapy. These patients do not receive any study specific medication. | |
| T2DM patients treated with DPP-4 + MET | T2DM patients treated with Dipeptidylpeptidase 4 inhibitors (DPP-4) + Metformin(MET) in their routine antidiabetic therapy. These patients do not receive any study specific medication. | |
| Healthy subjects | healthy volunteres who do not receive any antidiabetic medication in their routine therapie. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Investigation of ß-cell function via comparison of AUC0-300 minutes of intact Proinsulin in T2DM patients treated with LANTUS + Metformin (MET) vs. T2DM patients treated with Sulfonylurea (SU) + Metformin
Comparison of AUC0-300 min [intact Proinsulin] between T2DM patients treated with LANTUS + Metformin and T2DM patients treated with Sulfonylurea + MET after uptake of standardized meal
Measured: 0-300 minutes after standardized meal
Secondary outcomes (1)
Investigation of insulin, intact proinsulin, glucose and PAI-1 levels over a 5 h period after uptake of a standardized meal comparing four different population groups
Comparison of the AUC0-300 of intact proinsulin between each of the 4 treatment groups with the exception of T2DM patients treated with LANTUS + MET and T2DM patients treated with SU + MET after uptake of a standardized meal.
Comparison of the AUC0-300 for insulin, the AUC0-300 and the AUC0-180 for blood glucose, the mean maximum levels of intact proinsulin, insulin and BG, and the PAI-1 level excursion at the time points 0, 150 and 300 min between each of the 4 treatment groups.
Comparison of the change in the insulin/intact proinsulin ratio between each of the 4 treatment groups
Measured: 0-300 minutes after standardized meal
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2010 (estimated)
- Study startNov 2009
- Primary completionJul 2010
- Study completionJul 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes Mellitus, Type 2Studies 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 106 participants (actual)
Sponsor and investigators
- Lead sponsor
- ikfe-CRO GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Sanofi, IKFE Institute for Clinical Research and Development
- Investigators
- Thomas Forst, Prof. MD, Principal investigator, IKFE Institute for Clinical Research and Development
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01206712
- Sponsor's protocol ID
- SAN-FORST-001
- Status last verified
- Sep 2010
- First submitted
- 21 Sep 2010
- Last updated
- 22 Sep 2010
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Beta Cell Relieving and Cardiovascular Protective Effects of LANTUS Treatment in Type 2 Diabetes Patients - Investigation on Postprandial Excursions of Proinsulin and PAI-1 Levels
- ClinicalTrials.gov ID
- NCT01206712
- Acronym / sponsor ID
- SAN-FORST-001
- Conditions
- Diabetes Mellitus, Type 2
- Keywords
- Diabetes Mellitus Type 2, insulin glargine, Metformin
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 106 participants (actual)
- Lead sponsor
- ikfe-CRO GmbHIndustry (pharma, biotech, devices)
- Collaborators
- Sanofi, IKFE Institute for Clinical Research and Development
- Study start
- Nov 2009
- Primary completion
- Jul 2010 (actual)
- Study completion
- Jul 2010 (actual)
- First posted
- 22 Sep 2010 (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 phase IV clinical trial is to investigate the effect of Insulin glargine + metformin treatment vs. sulfonylurea + metformin treatment vs. DPP-4 + metformin treatment vs. healthy volunteers on ß-cell function after the uptake of a standardized meal.
Detailed description
Type 2 diabetes mellitus is a progressive disease characterised by a steady loss of beta cell function and an increase in the proinsulin/insulin ratio. During the recent years intact proinsulin has been the topic of interest in numerous preclinical and clinical studies in patients with type 2 diabetes mellitus. Intact proinsulin was confirmed as a marker of functional beta cell failure and as a predictor of increased beta cell loss due to apoptosis and/or diminished neogenesis.
A number of population based studies showed that intact proinsulin is a strong predictor of coronary heart disease in diabetic, and in non-diabetic patients. In a clinical trial investigating human proinsulin as a therapeutic approach for the treatment of diabetes mellitus an eight fold increase in CVD was found during treatment with human proinsulin compared to human regular insulin, indicating a thrombo-embolic potential of intact proinsulin. In a recent investigation an association could be confirmed between increased proinsulin plasma concentrations and the severity of angiographical characterised CHD.
Even the exact mechanism how proinsulin is involved in the pathogenesis of atherosclerosis is not completely recognized, it was already shown that PAI-1 activity increases after proinsulin administration in vitro, and there is increasing evidence that the atherogenic effects of proinsulin might be linked to increasing plasminogen activator inhibitor-1 (PAI-1) levels with subsequent inhibition of fibrinolysis and an augmented thrombogenic potency.
Treatment with sulfonylurea increases intact proinsulin secretion, and in a couple of studies, sulfonylurea treatment was found to be associated with an increased cardiovascular risk. In contrast, several studies have shown that after the introduction of insulin treatment in type 2 diabetic patients intact proinsulin levels and plasma PAI 1 levels decline, indicating not only beta cell protection, but also antiatherogenic properties of insulin. In a recent study, we have shown that treatment with basal insulin in combination with metformin effectively reduces intact proinsulin levels, and that insulin glargine is superior to NPH insulin in controlling postprandial release of intact proinsulin over an entire day.
Recently a new therapeutic concept using DPP IV inhibitors in combination with metformin has been introduced in the treatment of type 2 diabetic patients. There is some evidence that, in the beta cell, DPP IV Inhibitors might improve the conversion of intact Proinsulin into Insulin and C-peptide and thereby reduce circulating intact proinsulin levels. Since the number of type 2 diabetic patients treated with DPP-IV inhibitors is steadily increasing, there is a need to generate more data on the postprandial release of intact proinsulin in patients treated with DPP-IV inhibitors compared to Insulin or sulfonylurea treatment.
The rationale of the study is to investigate the effect of glargine and metformin treatment compared to sulfonylurea and metformin treatment and compared to DPP-4 inhibitor and metformin treatment on postprandial intact proinsulin release and postprandial PAI-1 levels. Accompanying a comparison of postprandial intact proinsulin release and the time course of postprandial PAI-levels in between all three antidiabetic treatment groups and a non-diabetic control group will be performed as well.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| T2DM patients treated with LANTUS + MET | – | –T2DM patients treated with LANTUS + Metformin(MET) in their routine antidiabetic therapy. These patients do not receive any study specific medication. |
| T2DM patients treated with SU + MET | – | –T2DM patients treated with Sulfonylurea (SU) + Metformin(MET)in their routine antidiabetic therapy. These patients do not receive any study specific medication. |
| T2DM patients treated with DPP-4 + MET | – | –T2DM patients treated with Dipeptidylpeptidase 4 inhibitors (DPP-4) + Metformin(MET) in their routine antidiabetic therapy. These patients do not receive any study specific medication. |
| Healthy subjects | – | –healthy volunteres who do not receive any antidiabetic medication in their routine therapie. |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- * Group 1 (n=20): Healthy subjects * Group 2 (n=20): T2DM patients treated with continuous SU + MET therapy as individually prescriped by the primary care physicians * Group 3 (n=20): T2DM patients treated with continuous LANTUS + MET therapy as individually prescriped by the primary care physicians * Group 4 (n=20): T2DM patients treated with continuous DPP-4 + MET therapy as individually prescriped by the primary care physicians
Key inclusion criteria (7 listed)
- Inclusion criteria - applicable for T2DM group only:
- 1.1. Type 2 diabetes mellitus 1.2. Duration of T2DM between 3 and 15 years inclusively 1.3. HbA1c up to 7.5% inclusively 1.4. Treated with LANTUS+MET (Group LANTUS+MET) or SU+MET (Group SU+MET) or DPP-4+MET (Group DPP-4+MET) respectively during the past 6 months before entering the study 1.5. Treated on a stable antidiabetic dosage during the past 3 months before entering the study
- Inclusion criteria - applicable for healthy subject only:
- 2.1. Fasting blood glucose £ 100 mg/dl (5.6 mmol/l) 2.2. Oral Glucose Tolerance Test (OGTT) revealed no IGT or DM
- Age of 40-75 years inclusively
Key exclusion criteria (13 listed)
- Exclusion criteria - applicable for T2DM group only:
- 1.1. Type 1 diabetes mellitus 1.2. Treatment with any other insulin than LANTUS during the past 6 months in Group LANTUS+MET or with any kind of insulin during the past 3 months in Group SU+MET or Group DPP-4+MET before entering the study 1.3. Treatment with any kind of OAD except MET during the past 6 months in Group LANTUS+MET or with any kind of OAD except MET+SU during the past 3 months in Group SU+MET or with any kind of OAD except DPP-4+SU during the past 3 months in Group DPP-4+MET before entering the study 1.4. Major micro- or macro vascular complications as judged by the investigator
- Exclusion criteria - applicable for healthy subject only:
- 2.1. Type 1 or type 2 diabetes mellitus (checked by oGTT) 2.2. Impaired Glucose Tolerance (IGT, checked by oGTT) 2.3. Impaired Fasting Glucose (IFG, checked by oGTT)
- History of drug or alcohol abuse within the last five years prior to screening
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Investigation of ß-cell function via comparison of AUC0-300 minutes of intact Proinsulin in T2DM patients treated with LANTUS + Metformin (MET) vs. T2DM patients treated with Sulfonylurea (SU) + Metformin
Time frame: 0-300 minutes after standardized meal
Comparison of AUC0-300 min [intact Proinsulin] between T2DM patients treated with LANTUS + Metformin and T2DM patients treated with Sulfonylurea + MET after uptake of standardized meal
1 secondary outcome
Investigation of insulin, intact proinsulin, glucose and PAI-1 levels over a 5 h period after uptake of a standardized meal comparing four different population groups
Time frame: 0-300 minutes after standardized meal
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 22 Sep 2010.
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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.
Thomas Forst, Prof. MD principal investigator
IKFE Institute for Clinical Research and Development
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Diabetes Mellitus, Type 2, run by ikfe-CRO GmbH at 1 site in Germany.
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 13 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 22 Sep 2010. 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 Germany. 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.
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?
Investigation of ß-cell function via comparison of AUC0-300 minutes of intact Proinsulin in T2DM patients treated with LANTUS + Metformin (MET) vs. T2DM patients treated with Sulfonylurea (SU) + Metformin (time frame: 0-300 minutes after standardized meal). 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 22 Sep 2010.