Effects of Acarbose Versus Glibenclamide on MAGE and Oxidative Stress in Patients With Type 2 DM

This study has been completed.
Sponsor:
Collaborators:
Taipei Veterans General Hospital, Taiwan
Changhua Christian Hospital
Information provided by:
Taichung Veterans General Hospital
ClinicalTrials.gov Identifier:
NCT00417729
First received: January 1, 2007
Last updated: May 11, 2010
Last verified: May 2010

January 1, 2007
May 11, 2010
January 2007
January 2009   (final data collection date for primary outcome measure)
  • Mean Amplitude Glycemic Excursion [ Time Frame: before randomisation and end of study ] [ Designated as safety issue: No ]
    A Medtronic MiniMed Continuous Glucose Monitoring System (Northridge, CA) was used for continuous glucose measurements on an ambulatory basis for 72 consecutive hours and MAGE calculated from the dataset.
  • Oxidative stress [ Time Frame: before randomisation and end of study ] [ Designated as safety issue: No ]
    Spot urine was collected for measurement of 8-iso PGF2 alpha excretion rate.
  • Mean Amplitude Glycemic Excursion
  • Oxidative stress
Complete list of historical versions of study NCT00417729 on ClinicalTrials.gov Archive Site
  • HbA1c [ Time Frame: before randomisation and end of study ] [ Designated as safety issue: No ]
    Glycated hemoglobin for evaluation of efficacy of glycemic control.
  • fasting glucose [ Time Frame: before randomisation and end of study ] [ Designated as safety issue: No ]
    after an overnight fasting
  • Insulin response [ Time Frame: before randomisation and end of study ] [ Designated as safety issue: No ]
    Evaluation by meal tolerance test. Patients were asked to consume 1.5 cans of Ensure Liquid (266 kcal/can, caloric contribution: 64% carbohydrate, 14% fat, and 22% protein) after a 10-h overnight fasting. Blood samples were drawn at 0, 10, 20, 30, 60, 90, 120, and 180 minute relative to the meal ingestion for the measurements of glucose and insulin.
  • Fasting lipids [ Time Frame: before randomisation and end of study ] [ Designated as safety issue: No ]
    after an overnight fasting
  • hsCRP [ Time Frame: before randomisation and end of study ] [ Designated as safety issue: No ]
    high-sensitivity C-reactive protein
  • oxLDL [ Time Frame: before randomisation and end of study ] [ Designated as safety issue: No ]
    oxidized low-density lipoprotein
  • Adiponectin [ Time Frame: before randomisation and end of study ] [ Designated as safety issue: No ]
    Total and high-molecular weight adiponectin
  • HbA1c
  • fasting glucose,
  • Insulin response,
  • Fasting lipids,
  • Inflammatory molecules (ICAM, V-CAM, hsCRP),
  • oxLDL,
  • adiponectin,
  • urinary albumin excretion rate,
  • urinary 8-iso PGF2 alpha
Not Provided
Not Provided
 
Effects of Acarbose Versus Glibenclamide on MAGE and Oxidative Stress in Patients With Type 2 DM
Phase 4 Study Evaluation of the Effects of Acarbose Versus Glibenclamide on Mean Amplitude of Glycemic Excursions and Oxidative Stress in Patients With Type 2 Diabetes Insufficiently Controlled by Metformin

To compare effect of acarbose versus glibenclamide treatment on mean amplitude of glyclemic excursion and oxidative stress in diabetes individuals who failed to control their glucose by metformin therapy alone

This is a randomised and open-label study conducted in 2 medical centers in central part of Taiwan. Type 2 diabetic outpatients were eligible if they were aged 30-70 years, were on mono- or dual oral antidiabetic drugs for at least 3 months, and had a glycated hemoglobin (HbA1c) value between 7.0% and 11.0%. Patients who were treated with insulin or drugs that promote weight loss, had impaired renal (serum creatinine concentration greater than 132.6 μmol/l) or liver (AST or ALT 2.5 times upper limit of normal range) function, had a history of hemoglobinopathy or chronic anemia, or women of child-bearing potential without adequate contraception were excluded. All patients provided their informed consent before they were enrolled in this study.

After an 8-week period of metformin monotherapy (500 mg t.i.d.), all patients were randomised to add on either acarbose or glibenclamide. The doses of acarbose and glibenclamide were 50 mg t.i.d. and 2.5 mg t.i.d., respectively, for 4 weeks and force-titrated to 100 mg t.i.d. and 5 mg t.i.d., respectively, for the last 12 weeks. A complete 72 hours of glucose monitoring using a continuous glucose monitoring (CGM) system and meal tolerance test (MTT) after a 10-h overnight fasting were performed before randomisation and in the end of study. Morning urine samples were collected for measurement of 8-iso prostaglandin F2α (8-iso PGF2α), a commonly used parameter of oxidative stress (13-14). The primary objectives are the changes of MAGE obtained from CGM and urinary excretion rate of 8-iso PGF2α. The secondary objectives include changes of HbA1c, lipid profiles including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides, oxidized low-density lipoprotein (ox-LDL), high-sensitivity C-reactive protein (hs-CRP), total adiponectin, and high-molecular weight (HMW) adiponectin.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Diabetes Mellitus
Drug: Acarbose
After an 8-week period of metformin monotherapy (500 mg t.i.d.), all patients were randomised to add on either acarbose or glibenclamide. The doses of acarbose and glibenclamide were 50 mg t.i.d. and 2.5 mg t.i.d., respectively, for 4 weeks and force-titrated to 100 mg t.i.d. and 5 mg t.i.d., respectively, for the last 12 weeks.
Other Names:
  • acarbose
  • glibenclamide
Active Comparator: acarbose, glibenclamide
acarbose vs. glibenclamide (background metformin therapy)
Intervention: Drug: Acarbose
Wang JS, Lin SD, Lee WJ, Su SL, Lee IT, Tu ST, Tseng YH, Lin SY, Sheu WH. Effects of acarbose versus glibenclamide on glycemic excursion and oxidative stress in type 2 diabetic patients inadequately controlled by metformin: a 24-week, randomized, open-label, parallel-group comparison. Clin Ther. 2011 Dec;33(12):1932-42. doi: 10.1016/j.clinthera.2011.10.014. Epub 2011 Nov 10.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
51
January 2009
January 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients may be included in the clinical trial only if they meet all of the following criteria:

    1. Male or female outpatients;
    2. Age 30 - 70 years;
    3. Patients have failed to achieve glycemic control with diet, exercise and max. 2 OHA; Hemoglobin A1c level between 7.0 to 11.0 % at V1 and 7-11.5 % at V4.
    4. Diagnosis of diabetes mellitus is over a minimum 3-month period;
    5. All patients give written informed consent;
    6. For female patients of childbearing potential, the following criteria will be applied:
  • Using adequate contraception since last menses and will continue to use adequate contraception during the clinical trial.
  • Not lactating.
  • Negative pregnancy test (urine) within 7 days prior to the first dose of study medication. (Note: the inclusion criterion 6 does not apply to menopausal female).

Exclusion Criteria:

  • Patients will be excluded from the clinical trial for any of the following reasons:

    1. Patients with a serum creatinine concentration greater than 132.6 mmol/L (1.5 mg/dL) or liver function impairment (AST and ALT 2.5 times upper limit of normal range);
    2. Patients have laboratory test abnormality (biochemistry, hematology, or urinalysis), which in the investigator's opinion might confound the clinical trial. However, patients with hyperlipemia, elevated cholesterol or triglyceride levels, or lipid metabolism disorders are eligible;
    3. Use of chronic insulin therapy;
    4. Patients with medical conditions that could promote lactic acidosis, such as renal or hepatic disease, unstable angina, congestive heart failure (New York Heart Association Functional Classification III and IV), or chronic obstructive pulmonary disease, e.g. respiratory insufficiency, hypoxemic condition;
    5. Patients with a history of hypersensitivity to metformin hydrochloride, glibenclamide or acarbose;
    6. Patients receive an investigational drug within 30 days prior to admission to the clinical trial;
    7. Patients with significant alcohol, drug or medication abuse as judged by the investigator.
Both
30 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
Taiwan
 
NCT00417729
IRB951004/C06211
No
Wayne H-H Sheu, M.D., Ph.D., Taichung Veterans General Hospital, Taichung, Taiwan
Taichung Veterans General Hospital
  • Taipei Veterans General Hospital, Taiwan
  • Changhua Christian Hospital
Principal Investigator: Wayne H Sheu, MD, PhD Taichung Veterans General Hospital
Taichung Veterans General Hospital
May 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP