Clinical trial NCT01420692: The Effects of Insulin Detemir and Gliclazide-MR Treatments on Endothelial Functions in Patients With Type 2 Diabetes
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 2 Diabetes Mellitus
Keywords: Tip 2 DM
Endothelium
Gliclazide
Insulin detemir
Lead sponsor: Ankara University
Sponsor class: OTHER
Collaborators: name: Hacettepe University
name: The Scientific and Technological Research Council of Turkey
First posted: 2011-08-22
Enrollment: 64
Sex: ALL
Minimum age (years): 20
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: 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
timeFrame: The basal, 12th and 24th week after reaching the target glycemic levels
measure: 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
timeFrame: The basal, 12th and 24th week after reaching the target glycemic levels
Secondary outcomes:
measure: 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
timeFrame: The basal, 12th and 24th week after reaching the target glycemic levels
Other outcomes:
Locations:
city: Ankara
country: Turkey
facility: Ankara University Medical Faculty Dept. of Endocrinology and Metabolism
Study officials:
affiliation: Ankara University Medical Faculty Dept. of Endocrinology and Metabolism
name: Ugur Unluturk, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hacettepe University Instute of Oncology Dept. of Basic Oncology
name: Altug S Kesikli, MD. PhD.
role: PRINCIPAL_INVESTIGATOR
References: