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Effect of Linagliptin in Comparison With Glimepiride as Add on to Metformin on Postprandial Beta Cell Function, Postprandial Metabolism and Oxidative Stress in Patients With Type 2 Diabetes Mellitus

Primary Purpose

Diabetes Mellitus Type 2

Status
Unknown status
Phase
Phase 4
Locations
Germany
Study Type
Interventional
Intervention
Linagliptin
Glimepiride
Sponsored by
Marcus Borchert
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Diabetes Mellitus Type 2

Eligibility Criteria

45 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Diabetes mellitus type 2
  2. HbA1c > 6.5% - ≤ 8.5%
  3. HbA1c > 7.0% - ≤ 8.5% for those patients with a significant cardiovascular history
  4. Treatment with metformin at a maximum tolerated dose
  5. Age 45 - 75 years (inclusively)
  6. Patient consents that his/her family physician/diabetologist will be informed of trial participation.

Exclusion Criteria:

  1. Pretreatment with PPAR gamma agonists within the last three months
  2. History of type 1 diabetes
  3. Uncontrolled hypertension (systolic blood pressure >160 mmHg and/or diastolic blood pressure >90 mmHg)
  4. Acute infections
  5. Medical history of hypersensitivity to the study drugs or to drugs with similar chemical structures
  6. History of severe or multiple allergies
  7. Treatment with any other investigational drug within 3 months before trial entry.
  8. Progressive fatal disease
  9. History of drug or alcohol abuse in the past 2 years
  10. State after kidney transplantation
  11. Serum potassium > 5.5 mmol/L
  12. Pregnancy or breast feeding
  13. Sexually active woman of childbearing age not practicing a highly effective method of birth control as defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, hormonal IUDs, sexual abstinence or vasectomized partner.
  14. Acute myocardial infarction, open heart surgery or cerebral event (stroke/TIA) within the previous 30 days
  15. Any elective surgery during study participation
  16. Have had more than one unexplained episode of severe hypoglycemia (defined as requiring assistance of another person due to disabling hypoglycemia) within 6 months prior to screening visit
  17. History of pancreatitis
  18. History of dehydration, pre-coma diabeticum or diabetic ketoacidosis
  19. Acute or scheduled investigation with iodine containing radiopaque material
  20. Uncontrolled unstable angina pectoris
  21. History of pericarditis, myocarditis, endocarditis
  22. Recent pulmonary embolism
  23. Hemodynamic relevant aortic stenosis
  24. Aortic aneurysm
  25. Regular use of NSAID's (no acute use of NSAID within 48 hours before V2,V4,V5)
  26. Lack of compliance or other similar reason that, according to investigator, precludes satisfactory participation in the study
  27. History of 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 hematological disease as judged by the investigator
  28. Lactose intolerance
  29. Intake of Coumarin or coumarin derived compounds such as phenprocoumon (Marcumar) or warfarin (Coumadin, Warfant)

Sites / Locations

  • ikfe GmbHRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Glimepiride-ratiopharm

Trajenta

Arm Description

Glimepiride (1-4mg) as add on therapy

Linagliptin 5 mg as add on therapy

Outcomes

Primary Outcome Measures

Postprandial increase in intact Proinsulin levels (Peak, AUC)
Postprandial Proinsulin/Insulin Ratio
Fasting intact Proinsulin levels
Fasting Proinsulin/Insulin Ratio
Fasting Blood Glucose
Postprandial Blood Glucose Excursions (Peak; AUC)
Fasting Lipids
Postprandial Lipids
Fasting Erythrocyte Flexibility
Postprandial Erythrocyte Flexibility
Fasting GLP-1 levels
Postprandial GLP-1 levels
Fasting cGMP
Postprandial cGMP
Fasting Calcitonin
Fasting PAI-1 levels
Postprandial PAI-1 levels
Fasting ADMA levels
Postprandial ADMA levels
Fasting Malonyldialdehyd
fasting oxidatively modified nucleosides 8-oxodG and 8-oxoGuo

Secondary Outcome Measures

Hypoglycemic events
Body Weight

Full Information

First Posted
February 21, 2012
Last Updated
April 10, 2012
Sponsor
Marcus Borchert
Collaborators
ikfe-CRO GmbH, Boehringer Ingelheim
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1. Study Identification

Unique Protocol Identification Number
NCT01547104
Brief Title
Effect of Linagliptin in Comparison With Glimepiride as Add on to Metformin on Postprandial Beta Cell Function, Postprandial Metabolism and Oxidative Stress in Patients With Type 2 Diabetes Mellitus
Official Title
Effect of Linagliptin in Comparison With Glimepiride as Add on to Metformin on Postprandial Beta Cell Function, Postprandial Metabolism and Oxidative Stress in Patients With Type 2 Diabetes Mellitus
Study Type
Interventional

2. Study Status

Record Verification Date
April 2012
Overall Recruitment Status
Unknown status
Study Start Date
April 2012 (undefined)
Primary Completion Date
October 2012 (Anticipated)
Study Completion Date
October 2012 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Marcus Borchert
Collaborators
ikfe-CRO GmbH, Boehringer Ingelheim

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The goal of this mechanistic study is to investigate the effect of Linagliptin in comparison to Glimepiride as add on therapy on several parameters characterizing postprandial metabolism and oxidative stress in type 2 diabetic patients on stable control with metformin.
Detailed Description
The goal of this mechanistic study is to investigate the effect of Linagliptin in comparison to Glimepiride as add on therapy on several parameters characterizing postprandial metabolism and oxidative stress in type 2 diabetic patients on stable control with metformin. This mechanistic phase IV study has a prospective, comparative, open, randomized, two arm and exploratory design. Overall 40 Patients will be randomized to two treatment arms both receiving Metformin at a maximally tolerated dose. In addition to that both treatment groups will receive either an individually titrated dose of Glimepiride or 5mg once daily of Linagliptin. Subsequent to a standardized meal, several parameters reflecting beta cell function, metabolism and oxidative stress will be evaluated.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus Type 2

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Glimepiride-ratiopharm
Arm Type
Active Comparator
Arm Description
Glimepiride (1-4mg) as add on therapy
Arm Title
Trajenta
Arm Type
Experimental
Arm Description
Linagliptin 5 mg as add on therapy
Intervention Type
Drug
Intervention Name(s)
Linagliptin
Intervention Description
Linagliptin dosed 5 mg as add on therapy to an existing metformin therapy
Intervention Type
Drug
Intervention Name(s)
Glimepiride
Other Intervention Name(s)
Glimepirid-ratiopharm
Intervention Description
Glimepiride 1-4mg (individually dosed) as add on therapy to an existing metformin therapy
Primary Outcome Measure Information:
Title
Postprandial increase in intact Proinsulin levels (Peak, AUC)
Time Frame
30, 60, 90, 120, 150, 180, 210, 240, 270 300 mins post test meal procedure, 3 times within 12 weeks treatment
Title
Postprandial Proinsulin/Insulin Ratio
Time Frame
after 12 weeks treatment
Title
Fasting intact Proinsulin levels
Time Frame
after 12 weeks treatment
Title
Fasting Proinsulin/Insulin Ratio
Time Frame
after 12 weeks treatment
Title
Fasting Blood Glucose
Time Frame
after 12 weeks treatment
Title
Postprandial Blood Glucose Excursions (Peak; AUC)
Time Frame
30, 60, 90, 120, 150, 180, 210, 240, 270 300 mins post test meal procedure, 3 times within 12 weeks treatment
Title
Fasting Lipids
Time Frame
after 12 weeks treatment
Title
Postprandial Lipids
Time Frame
after 12 weeks treatment
Title
Fasting Erythrocyte Flexibility
Time Frame
after 12 weeks treatment
Title
Postprandial Erythrocyte Flexibility
Time Frame
after 12 weeks treatment
Title
Fasting GLP-1 levels
Time Frame
after 12 weeks treatment
Title
Postprandial GLP-1 levels
Time Frame
after 12 weeks treatment
Title
Fasting cGMP
Time Frame
after 12 weeks treatment
Title
Postprandial cGMP
Time Frame
after 12 weeks treatment
Title
Fasting Calcitonin
Time Frame
after 12 weeks treatment
Title
Fasting PAI-1 levels
Time Frame
after 12 weeks treatment
Title
Postprandial PAI-1 levels
Time Frame
after 12 weeks treatment
Title
Fasting ADMA levels
Time Frame
after 12 weeks treatment
Title
Postprandial ADMA levels
Time Frame
after 12 weeks treatment
Title
Fasting Malonyldialdehyd
Time Frame
after 12 weeks treatment
Title
fasting oxidatively modified nucleosides 8-oxodG and 8-oxoGuo
Time Frame
after 12 weeks treatment
Secondary Outcome Measure Information:
Title
Hypoglycemic events
Time Frame
after 12 weeks treatment
Title
Body Weight
Time Frame
after 12 weeks treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diabetes mellitus type 2 HbA1c > 6.5% - ≤ 8.5% HbA1c > 7.0% - ≤ 8.5% for those patients with a significant cardiovascular history Treatment with metformin at a maximum tolerated dose Age 45 - 75 years (inclusively) Patient consents that his/her family physician/diabetologist will be informed of trial participation. Exclusion Criteria: Pretreatment with PPAR gamma agonists within the last three months History of type 1 diabetes Uncontrolled hypertension (systolic blood pressure >160 mmHg and/or diastolic blood pressure >90 mmHg) Acute infections Medical history of hypersensitivity to the study drugs or to drugs with similar chemical structures History of severe or multiple allergies Treatment with any other investigational drug within 3 months before trial entry. Progressive fatal disease History of drug or alcohol abuse in the past 2 years State after kidney transplantation Serum potassium > 5.5 mmol/L Pregnancy or breast feeding Sexually active woman of childbearing age not practicing a highly effective method of birth control as defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, hormonal IUDs, sexual abstinence or vasectomized partner. Acute myocardial infarction, open heart surgery or cerebral event (stroke/TIA) within the previous 30 days Any elective surgery during study participation Have had more than one unexplained episode of severe hypoglycemia (defined as requiring assistance of another person due to disabling hypoglycemia) within 6 months prior to screening visit History of pancreatitis History of dehydration, pre-coma diabeticum or diabetic ketoacidosis Acute or scheduled investigation with iodine containing radiopaque material Uncontrolled unstable angina pectoris History of pericarditis, myocarditis, endocarditis Recent pulmonary embolism Hemodynamic relevant aortic stenosis Aortic aneurysm Regular use of NSAID's (no acute use of NSAID within 48 hours before V2,V4,V5) Lack of compliance or other similar reason that, according to investigator, precludes satisfactory participation in the study History of 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 hematological disease as judged by the investigator Lactose intolerance Intake of Coumarin or coumarin derived compounds such as phenprocoumon (Marcumar) or warfarin (Coumadin, Warfant)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Thomas Forst, MD, PhD
Phone
+ 49 6131 57636
Ext
16
Email
ThomasF@ikfe.de
First Name & Middle Initial & Last Name or Official Title & Degree
Claudia Forkel
Phone
+ 49 6131 32790
Ext
32
Email
C.Forkel@ikfe-cro.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas Forst, MD, PhD
Organizational Affiliation
Ikfe GmbH
Official's Role
Principal Investigator
Facility Information:
Facility Name
ikfe GmbH
City
Mainz
State/Province
Rhineland-Palatinate
ZIP/Postal Code
55116
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thomas Forst, MD, PhD
Phone
+ 49 6131 57636
Ext
16
Email
ThomasF@ikfe.de
First Name & Middle Initial & Last Name & Degree
Daniela Sachsenheimer, MD
Phone
+ 49 6131 57636
Ext
46
Email
DanielaS@ikfe.de
First Name & Middle Initial & Last Name & Degree
Daniela Sachsenheimer, MD
First Name & Middle Initial & Last Name & Degree
Stephanie Helleberg, MD
First Name & Middle Initial & Last Name & Degree
Stefan Diessel
First Name & Middle Initial & Last Name & Degree
Michael Mitry, MD

12. IPD Sharing Statement

Learn more about this trial

Effect of Linagliptin in Comparison With Glimepiride as Add on to Metformin on Postprandial Beta Cell Function, Postprandial Metabolism and Oxidative Stress in Patients With Type 2 Diabetes Mellitus

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