The Effects of Insulin Detemir and Gliclazide-MR Treatments on Endothelial Functions in Patients With Type 2 Diabetes

This study has been completed.
Sponsor:
Collaborators:
Hacettepe University
Tubitak
Information provided by (Responsible Party):
Ugur Unluturk, Ankara University
ClinicalTrials.gov Identifier:
NCT01420692
First received: October 28, 2010
Last updated: August 13, 2012
Last verified: August 2012
  Purpose

The main purpose of this study is to analyze the effects of the addition of sulfonylurea (gliclazide MR) or ,alternatively, basal insulin (insulin detemir) to life-style modification and metformin treatment as a second step treatment in type 2 diabetes mellitus on endothelial cell functions. The second goal is to identify the effects of these treatment alternatives on body-mass index, the changes in body fat mass, insulin resistance and on the insulin secretion capacity of beta cells. The third aim of this study is to determine the success rates of these treatment alternatives on glycemic control at 6 months follow-up.


Condition Intervention
Type 2 Diabetes Mellitus
Drug: Gliclazide MR
Drug: Insulin Detemir

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Effects of Insulin Detemir and Gliclazide-MR Treatments in Addition to Life-style Modification and Metformin Therapy on Endothelial Functions in Patients With Type 2 Diabetes : An Open-labelled Randomized Prospective Study

Resource links provided by NLM:


Further study details as provided by Ankara University:

Primary Outcome Measures:
  • The evaluation of the changes in Flow-Mediated Dilatation (FMD) at 12th and 24th weeks compared to the baseline level, as a Measure of Endothelial Function [ Time Frame: The basal, 12th and 24th week after reaching the target glycemic levels ] [ Designated as safety issue: No ]
    As soon as type 2 DM patients which were randomly recruited either to the Gliclazide MR arm or the Insulin Detemir arm reach to target glycemic levels (0. week), flow-mediated dilatation test, which is a basal tests showing endothelial function will be performed. This basal test will be reapeated in each study subject, 12 weeks and 24 weeks after reaching the target glycemic levels.

  • The Changes in the Peripheral Blood Levels of TNF-α, IL-6, MCP-1, sICAM-1, sVCAM-1, vWF, E-selectin, P-selectin, Endothelin-1, PAI-1, tPA and HMW Adiponectin at 12th and 24th weeks compared to the baseline level, as Measures of Inflam. and Coagulation [ Time Frame: The basal, 12th and 24th week after reaching the target glycemic levels ] [ Designated as safety issue: No ]
    As soon as type 2 DM patients which were randomly recruited either to the Gliclazide MR arm or the Insulin Detemir arm reach to target glycemic levels (0. week), basal tests showing endothelial function as well as inflammatory and coagulation status such as flow-mediated dilatation and peripheral blood TNF-α, IL-6, MCP-1, sICAM-1, sVCAM-1, vWF, E-selectin, P-selectin, endothelin-1, PAI-1, tPA and HMW adiponectin levels will be performed. These basal tests will be reapeated in each study subject, 12 weeks and 24 weeks after reaching the target glycemic levels.


Secondary Outcome Measures:
  • Calculation of Body-mass Index, Body Fat Mass, Level of Insulin Resistance and the Insulin Secretion Capacity of Pancreatic Beta Islet Cells as Measures to Identify the Effects of Gliclazide and Insulin Detemir Treatments on Diabetes Progression [ Time Frame: The basal, 12th and 24th week after reaching the target glycemic levels ] [ Designated as safety issue: No ]
    As soon as type 2 DM patients which were randomly recruited either to the Gliclazide MR arm or the Insulin Detemir arm reach to target glycemic levels (0. week), mixed-meal test and body-fat mass determination using bioimpedence analysis will be performed. These tests will be reapeated in each study subject, 12 weeks and 24 weeks after reaching the target glycemic levels.


Enrollment: 64
Study Start Date: June 2010
Study Completion Date: June 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Gliclazide MR Drug: Gliclazide MR
Doses between 30 mg to 120 mg/day p.o. Gliclazide MR will be arranged according to the target glycemic levels.
Other Name: Diamicron MR
Active Comparator: Insulin Detemir
Early initiation of insulin detemir in contrast to Gliclazide MR treatment
Drug: Insulin Detemir
Early initiation of s.c. insulin detemir in contrast to Gliclazide MR. Insulin detemir treatment will be exchanged to Gliclazide MR after 12 weeks.
Other Name: Levemir Flexpen

Detailed Description:

The lack of enough number of randomized and controlled studies in the treatment of type 2 diabetes is the most important obstacle in recommending a single-drug or a combination treatment to the other.

The pleomorphic effects of the treatment choices other than the control of hyperglycemia in type 2 diabetes are equally important. There is yet a lack of the comparison of different treatment alternatives found in the treatment algorithms of American Diabetes Association (ADA) both in terms of the effects on hyperglycemia control as well as other pleomorphic effects. Some of these pleomorphic effects are the change in body-mass index, insulin resistance, insulin secretion capacity and the effects on endothelial functions and coagulation status.

This study is mainly prepared to analyze the effects of the addition of sulfonylurea (gliclazide MR) or alternatively basal insulin (insulin detemir) to life-style modification and metformin treatment as a second step treatment in type 2 diabetes mellitus treatment algorithm on endothelial cell functions. The second goal is to identify the effects of these treatment alternatives on body-mass index, the changes in body fat mass, insulin resistance and on the insulin secretion capacity of beta cells. The third aim of this study is to determine the success rates of these treatment alternatives on glycemic control at 6 months follow-up. This study in this sense is expected to shed the light on the decision of best treatment option as well as an essential contribution to the lacking literature in the field.

To reach these aims, 20-65 year-old patients applying to the endocrinology and the metabolism outpatient unit, having type 2 diabetes diagnoses with unregulated blood glucose levels after first step treatment (life-style modification and metformin) will be recruited and randomized either to the Gliclazide MR arm or the Insulin Detemir arm. As soon as patients in each arm reach to the target glycemic levels (0. week), basal tests showing endothelial function as well as inflammatory and coagulation status such as flow-mediated dilatation (FMD)and investigation of the peripheral blood levels of TNF-α, IL-6, MCP-1, sICAM-1, sVCAM-1, vWF, E-selectin, P-selectin, endothelin-1, PAI-1, tPA and HMW adiponectin will be performed. To investigate the insulin resistance and the changes in insulin secretory capacity of beta cells, mixed meal test will be performed and data obtained about glucose as well as insulin levels during mixed meal test will be evaluated. To identify the changes in body-fat mass, bioimpedance analyses will also be performed. All these basal tests will be repeated in each study subject, 12 weeks and 24 weeks after reaching the target glycemic levels. Patients randomized to insulin detemir arm in the beginning will only have gliclazide MR treatment after the 12.week tests are performed. The effects of continuous gliclazide MR treatment or early insulin detemir followed by gliclazide MR treatment on endothelial cell functions, inflammation and coagulation, insulin resistance, insulin secretory capacity of beta cells and body-fat mass will be evaluated by comparing the 0. week with 12. and 24. week values within each arm as well as 24. week values between arms.

  Eligibility

Ages Eligible for Study:   20 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Type 2 diabetic patients using at least 1000 mg/day metformin at least for 3 months
  2. 7<A1C ≤ 11
  3. Patients without any previous use of oral antidiabetics other than metformin or insulin
  4. Between 20 to 65 years old male or female patients

Exclusion Criteria:

  1. Active hepatic disease
  2. Serum creatinin 1,5 mg/dl or more for males, 1,4 or more for females
  3. Proliferative Diabetic Retinopathy
  4. Coronary Artery Disease
  5. Patients with any kind of diagnosed malignancy
  6. Pregnancy and Lactation
  7. Fasting C-peptide levels lower than 2.0 ng/ml
  8. Smoking or drug abuse
  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: NCT01420692

Locations
Turkey
Ankara University Medical Faculty Dept. of Endocrinology and Metabolism
Ankara, Turkey, 06100
Sponsors and Collaborators
Ankara University
Hacettepe University
Tubitak
Investigators
Principal Investigator: Ugur Unluturk, MD Ankara University Medical Faculty Dept. of Endocrinology and Metabolism
Principal Investigator: Altug S Kesikli, MD. PhD. Hacettepe University Instute of Oncology Dept. of Basic Oncology
  More Information

Additional Information:
No publications provided

Responsible Party: Ugur Unluturk, Medical Doctor, Endocrinology and Metabolism, Ankara University
ClinicalTrials.gov Identifier: NCT01420692     History of Changes
Other Study ID Numbers: 110S119
Study First Received: October 28, 2010
Last Updated: August 13, 2012
Health Authority: Turkey: Tubitak

Keywords provided by Ankara University:
Tip 2 DM
Endothelium
Gliclazide
Insulin detemir

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

ClinicalTrials.gov processed this record on September 18, 2014