Clinical trial NCT00417729: Effects of Acarbose Versus Glibenclamide on MAGE and Oxidative Stress in Patients With Type 2 DM
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetes Mellitus
Keywords: Diabetes
Acarobse
Metformin
oxidative stress
Mean amplitude Glycemic Excursion
Meal test
Lead sponsor: Taichung Veterans General Hospital
Sponsor class: OTHER
Collaborators: name: Taipei Veterans General Hospital, Taiwan
name: Changhua Christian Hospital
First posted: 2007-01-04
Enrollment: 51
Sex: ALL
Minimum age (years): 30
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Mean Amplitude Glycemic Excursion
timeFrame: before randomisation and end of study
measure: Oxidative stress
timeFrame: before randomisation and end of study
Secondary outcomes:
measure: HbA1c
timeFrame: before randomisation and end of study
measure: fasting glucose
timeFrame: before randomisation and end of study
measure: Insulin response
timeFrame: before randomisation and end of study
measure: Fasting lipids
timeFrame: before randomisation and end of study
measure: hsCRP
timeFrame: before randomisation and end of study
measure: oxLDL
timeFrame: before randomisation and end of study
measure: Adiponectin
timeFrame: before randomisation and end of study
Other outcomes:
Locations:
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
Study officials:
affiliation: Taichung Veterans General Hospital
name: Wayne H Sheu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chen PH, Tsai YT, Wang JS, Lin SD, Lee WJ, Su SL, Lee IT, Tu ST, Tseng YH, Sheu WH, Lin SY. Post-meal beta-cell function predicts the efficacy of glycemic control in patients with type 2 diabetes inadequately controlled by metformin monotherapy after addition of glibenclamide or acarbose. Diabetol Metab Syndr. 2014 May 31;6:68. doi: 10.1186/1758-5996-6-68. eCollection 2014.
citation: 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.