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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

This study is currently recruiting participants.
Verified April 2012 by ikfe-CRO GmbH
Sponsor:
Collaborators:
ikfe-CRO GmbH
Boehringer Ingelheim Pharmaceuticals
Information provided by (Responsible Party):
Marcus Borchert, ikfe-CRO GmbH
ClinicalTrials.gov Identifier:
NCT01547104
First received: February 21, 2012
Last updated: April 10, 2012
Last verified: April 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus Type 2
 Drug: Linagliptin
Drug: Glimepiride
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by ikfe-CRO GmbH:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Postprandial Proinsulin/Insulin Ratio [ Time Frame: after 12 weeks treatment ] [ Designated as safety issue: No ]
  • Fasting intact Proinsulin levels [ Time Frame: after 12 weeks treatment ] [ Designated as safety issue: No ]
  • Fasting Proinsulin/Insulin Ratio [ Time Frame: after 12 weeks treatment ] [ Designated as safety issue: No ]
  • Fasting Blood Glucose [ Time Frame: after 12 weeks treatment ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Fasting Lipids [ Time Frame: after 12 weeks treatment ] [ Designated as safety issue: No ]
  • Postprandial Lipids [ Time Frame: after 12 weeks treatment ] [ Designated as safety issue: No ]
  • Fasting Erythrocyte Flexibility [ Time Frame: after 12 weeks treatment ] [ Designated as safety issue: No ]
  • Postprandial Erythrocyte Flexibility [ Time Frame: after 12 weeks treatment ] [ Designated as safety issue: No ]
  • Fasting GLP-1 levels [ Time Frame: after 12 weeks treatment ] [ Designated as safety issue: No ]
  • Postprandial GLP-1 levels [ Time Frame: after 12 weeks treatment ] [ Designated as safety issue: No ]
  • Fasting cGMP [ Time Frame: after 12 weeks treatment ] [ Designated as safety issue: No ]
  • Postprandial cGMP [ Time Frame: after 12 weeks treatment ] [ Designated as safety issue: No ]
  • Fasting Calcitonin [ Time Frame: after 12 weeks treatment ] [ Designated as safety issue: No ]
  • Fasting PAI-1 levels [ Time Frame: after 12 weeks treatment ] [ Designated as safety issue: No ]
  • Postprandial PAI-1 levels [ Time Frame: after 12 weeks treatment ] [ Designated as safety issue: No ]
  • Fasting ADMA levels [ Time Frame: after 12 weeks treatment ] [ Designated as safety issue: No ]
  • Postprandial ADMA levels [ Time Frame: after 12 weeks treatment ] [ Designated as safety issue: No ]
  • Fasting Malonyldialdehyd [ Time Frame: after 12 weeks treatment ] [ Designated as safety issue: No ]
  • fasting oxidatively modified nucleosides 8-oxodG and 8-oxoGuo [ Time Frame: after 12 weeks treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Hypoglycemic events [ Time Frame: after 12 weeks treatment ] [ Designated as safety issue: Yes ]
  • Body Weight [ Time Frame: after 12 weeks treatment ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 40
Study Start Date: April 2012
Estimated Study Completion Date: October 2012
Estimated Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Glimepiride-ratiopharm
Glimepiride (1-4mg) as add on therapy
 Drug: Glimepiride
Glimepiride 1-4mg (individually dosed) as add on therapy to an existing metformin therapy
Other Name: Glimepirid-ratiopharm
Experimental: Trajenta
Linagliptin 5 mg as add on therapy
 Drug: Linagliptin
Linagliptin dosed 5 mg as add on therapy to an existing metformin therapy

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.

  Eligibility

Ages Eligible for Study:   45 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01547104

Contacts
Contact: Thomas Forst, MD, PhD + 49 6131 57636 ext 16 ThomasF@ikfe.de
Contact: Claudia Forkel + 49 6131 32790 ext 32 C.Forkel@ikfe-cro.de

Locations
Germany
ikfe GmbH Recruiting
Mainz, Rhineland-Palatinate, Germany, 55116
Contact: Thomas Forst, MD, PhD     + 49 6131 57636 ext 16     ThomasF@ikfe.de    
Contact: Daniela Sachsenheimer, MD     + 49 6131 57636 ext 46     DanielaS@ikfe.de    
Sub-Investigator: Daniela Sachsenheimer, MD            
Sub-Investigator: Stephanie Helleberg, MD            
Sub-Investigator: Stefan Diessel            
Sub-Investigator: Michael Mitry, MD            
Sponsors and Collaborators
Marcus Borchert
ikfe-CRO GmbH
Boehringer Ingelheim Pharmaceuticals
Investigators
Principal Investigator: Thomas Forst, MD, PhD Ikfe GmbH
  More Information

No publications provided

Responsible Party: Marcus Borchert, Prof. Dr. Thomas Forst, ikfe-CRO GmbH
ClinicalTrials.gov Identifier: NCT01547104     History of Changes
Other Study ID Numbers: ikfe-Lina-002, 2012-000179-17
Study First Received: February 21, 2012
Last Updated: April 10, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Glimepiride
BI 1356
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
 Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 16, 2013