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

Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00417729
• Other study ID #: IRB951004/C06211
• Status: Completed
• Phase: Phase 4
• First received: January 1, 2007
• Last updated: May 11, 2010
• Start date: January 2007
• Est. completion date: January 2009

Study information

• Verified date: May 2010
• Source: Taichung Veterans General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Taiwan: Department of Health
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: January 2009
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 70 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus

Intervention

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.

Locations

Country	Name	City	State
Taiwan	Taichung Veterans General Hospital	Taichung

Sponsors (3)

Lead Sponsor	Collaborator
Taichung Veterans General Hospital	Changhua Christian Hospital, Taipei Veterans General Hospital, Taiwan

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Amplitude Glycemic Excursion	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.	before randomisation and end of study	No
Primary	Oxidative stress	Spot urine was collected for measurement of 8-iso PGF2 alpha excretion rate.	before randomisation and end of study	No
Secondary	HbA1c	Glycated hemoglobin for evaluation of efficacy of glycemic control.	before randomisation and end of study	No
Secondary	fasting glucose	after an overnight fasting	before randomisation and end of study	No
Secondary	Insulin response	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.	before randomisation and end of study	No
Secondary	Fasting lipids	after an overnight fasting	before randomisation and end of study	No
Secondary	hsCRP	high-sensitivity C-reactive protein	before randomisation and end of study	No
Secondary	oxLDL	oxidized low-density lipoprotein	before randomisation and end of study	No
Secondary	Adiponectin	Total and high-molecular weight adiponectin	before randomisation and end of study	No