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Feasibility of Once/Daily Administered GLP/1 Receptoragonist (Lixisenatide) in Combination With Basal Insulin (LixiBIT)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2014 by Medical University of Vienna
Sponsor:
Information provided by (Responsible Party):
Prof. Dr. Michael Krebs, Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT02168491
First received: June 12, 2014
Last updated: November 15, 2014
Last verified: November 2014
  Purpose

Premixed insulin-based therapy is a standard insulin treatment strategy in Austria. The widespread use of premixed insulin is explained by high acceptance by health care professionals and patients due to one single product and flexible number of injections (1-3 daily) which covers the demand in controlling fasting and postprandial glucose excursions of most patients with diabetes. However, the use of pre-mixed insulin frequently leads to a high insulin demand and consequently weight gain and an increased risk of hypoglycemia. Hence, achieve good metabolic control in these patients remains a major challenge.

For those patients, the approach to treatment intensification without facing the typical risks of insulin treatment (hypoglycemia and weight increase) is of major importance. One, so far not exploited option may be the BIT-strategy: Basal insulin in combination with incretin-based therapy.

Pathophysiologically basal insulin inhibits glucose production in the liver, decreases hepatic insulin resistance and improves the function of beta cells in the postprandial state by discharge of fasting insulin secretion. During further diabetes progression steadily increasing HbA1c levels - despite good fasting blood glucose control - indicate the need for additional intervention of meal-related glucose excursions. In this stage of type-2 diabetes basal insulin can be combined with prandial (short-acting) insulin or prandial GLP-1 receptor agonists. However, regarding important safety parameters: risks of hypoglycemia and weight gain in the long-term treatment GLP-1 receptor agonists are beneficial.

Lixisenatide is a novel GLP-1 receptor agonist with a pronounced postprandial (PPG) effect which fits with basal insulin mode of action primarily focused on fasting blood glucose reduction.

Therefore 10 patients (both gender) under treatment with premixed insulin (2-3 times daily) and HbA1c>7% will be switched to basal insulin glargine (Lantus, once daily) and GLP-1 receptor agonist Lixisenatide (Lyxumia, once daily). The investigators hypothesize that switching from a therapy based on premixed insulin to a simple, once daily administered combination of basal insulin plus a GLP-1 receptor agonist in patients with type-2 diabetes not achieving therapeutic target (HbA1c>7%) is clinically feasable in an out patient setting


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Lixisenatide
Drug: Insulin glargine
Phase 3

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Feasibility of Once-daily Administered GLP-1 Receptoragonist (Lixisenatide) in Combination With Basal Insulin in Patients With Type-2 Diabetes Mellitus Not Achieving Therapeutic Targets With Premixed Insulin

Resource links provided by NLM:


Further study details as provided by Medical University of Vienna:

Primary Outcome Measures:
  • Change in HbA1c from baseline to end [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    HbA1c, fasting plasma glucose, anthropometric parameters (height, weight, waist circumference), blood pressure and heart rate will be measured at baseline and 2, 4, 8 and 12 weeks.


Secondary Outcome Measures:
  • Change in fasting plasma glucose (FPG, mean over 2 weeks) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

    Patients will be instructed to record all insulin injections and a complete 7-point-blood glucose profile (fasting, 2h after breakfast, before lunch, 2h after lunch, before dinner, 2h after dinner, late before going to bed) during a one-week prestudy run-in period to confirm compliance and document current metabolic control and doses of premixed insulin.

    Patients will be asked to record not only glucose profiles (at least 4 measurements per day) but also the occurrence of hypoglycemic symptoms or other adverse effects daily throughout the study.

    During the last week of the study patients will be asked to again record a complete 7-point-blood glucose profile (fasting, 2h after breakfast, before lunch, 2h after lunch, before dinner, 2h after dinner, late before going to bed) and drug injections to confirm compliance and document metabolic control.


  • Change in body weight from baseline to end of study [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    HbA1c, fasting plasma glucose, anthropometric parameters (height, weight, waist circumference), blood pressure and heart rate will be measured at baseline and 2, 4, 8 and 12 weeks.


Estimated Enrollment: 10
Study Start Date: November 2014
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intervention group
10 type 2 diabetic patients will be included to perform in this study and will be switched from premixed insulin to insulin glargine and lixisenatide
Drug: Lixisenatide
Patients will be switched to basal insulin glargine (Lantus, once daily in the morning) and GLP-1 receptor agonist Lixisenatide (Lyxumia, once daily in the morning before breakfast; days 1-14 10 µg thereafter 20 µg). The (mean) daily dose of premixed insulin will be calculated based on the records of the run in period. The initial dose of insulin glargine will be adjusted at about 60% of the daily insulin dose of premixed insulin. This is based on the observed reduction of required insulin dose described in recent literature upon initiation with a GLP-1 agonist.
Other Name: Lyxumia
Drug: Insulin glargine
Patients will be switched to basal insulin glargine (Lantus, once daily in the morning) and GLP-1 receptor agonist Lixisenatide (Lyxumia, once daily in the morning before breakfast; days 1-14 10 µg thereafter 20 µg). The (mean) daily dose of premixed insulin will be calculated based on the records of the run in period. The initial dose of insulin glargine will be adjusted at about 60% of the daily insulin dose of premixed insulin. This is based on the observed reduction of required insulin dose described in recent literature upon initiation with a GLP-1 agonist.
Other Name: Lantus

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18 - 70a
  • Subjects understand study related activities and give written informed concent
  • HbA1c between 7 - 10 % under treatment with premixed insulin (2-3 injections)

Exclusion Criteria:

  • Females of child-bearing age
  • History of hypoglycemia unawareness
  • Gastrointestinal disease associated with prolonged nausea and vomiting
  • Impaired liver function (transaminase >2x than normal)
  • Impaired kidney function (creatinin > 1,2 mg/dl)
  • Known intolerance against GLP-1 receptor agonists
  • History of pancreatitis or pancreas tumor
  • Malignancies, autoimmune diseases
  • Severe dyslipidemia (serum triglycerides > 400 mg/dl, cholesterol > 300 mg/dl)
  • Psychiatric disorder
  • Oral glucose lowering medication except for metformin
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02168491

Contacts
Contact: Peter Wolf, MD 00431404004311 peter.wolf@meduniwien.ac.at
Contact: Michael Krebs, MD, Prof 00431404004311 michael.krebs@meduniwien.ac.at

Locations
Austria
Medical University Of Vienna, Department of Internal Medicine III Recruiting
Vienna, Austria, 1090
Contact: Peter Wolf, MD    00431404004311    peter.wolf@meduniwien.ac.at   
Contact: Michael Krebs, MD, Prof    00431404004311    michael.krebs@meduniwien.ac.at   
Principal Investigator: Michael Krebs, MD, Prof         
Sub-Investigator: Peter Wolf, MD         
Sub-Investigator: Yvonne Winhofer, MD, PhD         
Sub-Investigator: Anton Luger, MD, Prof         
Sub-Investigator: Bernhard Ludvik, MD, Prof         
Sponsors and Collaborators
Medical University of Vienna
Investigators
Principal Investigator: Michael Krebs, MD, Prof. Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
  More Information

No publications provided

Responsible Party: Prof. Dr. Michael Krebs, Prof. MD, Medical University of Vienna
ClinicalTrials.gov Identifier: NCT02168491     History of Changes
Other Study ID Numbers: LixiBIT_V3, 2013-005334-37
Study First Received: June 12, 2014
Last Updated: November 15, 2014
Health Authority: Austria: Austrian Agency for Health and Food Safety (AGES)

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Glargine
Insulin
Insulin, Globin Zinc
Insulin, Long-Acting
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 23, 2014