A Study for Sufficient Acarbose Decreased Glucose Excursion in Type 2 Diabetic Patients

• Conditions: Type 2 Diabetes Mellitus; Poor Glycemic Control

• Registration Number: NCT03805191
• Lead Sponsor: Qilu Hospital of Shandong University

Brief Summary

This is a multicentre observational study to investigate the improvement in glucose fluctuation of sufficient acarbose therapy on type 2 diabetes patient with high blood glucose fluctuation

Detailed Description

Acarbose competitively inhibits the a-glycosidase on the surface of epithelial cells from the duodenum and small intestine, delays the metabolism and assimilation of carbohydrates, and thus effectively decreases postprandial blood glucose(PBG) as well as the risk of hypoglycemia before the next meal.Acarbose is now used as the preferred drug for some patients with prediabetes and newly diagnosed type 2 diabetes millitus(T2DM).This study aims to investigate the glycemic excursions with different courses and glycated hemoglobin A1c(HbA1c) levels after treated three months with acarbose.To minimize gastrointestinal side effects，starting dosage of acarbose of 50 mg is given orally three times daily for 10 days(with the first bite) of each main meal. Glycemic excursions are evaluated using the mean amplitude of glycemic excursions (MAGE), the postprandial glycemic excursions (PPGE) and the largest amplitude of glycemic excursions (LAGE).Freestyle Libre flash glucose monitoring system (FGMS，Abbott Laboratories,USA) was administered in this study. According to the standard Freestyle Libre Pro operating guidelines, the FGMS is installed in all participants to monitor glucose levels of interstitial fluid for 14 consecutive days. The glucose sensor is inserted into the subcutaneous tissue of upper arm at 8:00-9:00 in the morning.Glucose concentrations at 7 preset times per day (before meals, 2-h after meals and at bedtime) were determined with VivaChek Ino Smart（VivaChek Laboratories, Inc., USA) every two weeks.Four days before using acarbose and five weeks after using acarbose, FGMS was using to monitor the continuous glucose.MAGE was calculated for each subject by taking the arithmetic mean of FGM values increased or decreased (from nadirs to peaks or vice versa) when both ascending and descending segments exceeded the value of one standard deviation (SD) of the FGM values for 24-h period.The primary endpoint of the study is the extent of change in MAGE.Secondary endpoints are changes in PPGE,LAGE and HbA1c. Gene polymorphism is detected for enrolled patient with poor acarbose effect.

Study Timeline

• Study Start: 2019-01-01
• Study First Submitted: 2019-01-10
• Study First Submitted QC: 2019-01-13
• Study First Posted: 2019-01-15
• Status Verified: 2019-04
• Last Update Submitted: 2019-04-11
• Last Update Posted: 2019-04-12
• Primary Completion: 2020-11-30
• Study Completion: 2022-12-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 900

Inclusion Criteria

1. All enrolled patients sign the informed consent. sign the informed consent form.
2. Clinical diagnosis of T2DM(1999 WHO).
3. No acarbose in nearly 3 months.
4. 7% < HbA1c ≤10% .
5. PPGE >2.2mmol/L and LAGE >4.4mmol/L.
6. MAGE > 3.9 mmol/L.
7. The previous therapy remain the same.
8. Contraception is needed for women of child-bearing age until 28 days after the end.

Exclusion Criteria

1. Women of childbearing potential unable or unwilling to use acceptable birth control, or women who are pregnant or breastfeeding.

2. Replacement or chronic systemic corticosteroid therapy. Cytochrome P450 3A4 enzyme inducer or inhibitor therapy.Antiviral therapy for immunodeficiency disease.

3. History of gastrointestinal disease or surgery including Roemheld Syndrome, severe hernia, intestinal obstruction, intestinal ulcer, gastroenterostomy, enterectomy, bariatric surgery or lap-band procedure.

4. Known immunocompromised status, including but not limited to, individuals who had undergone organ transplantation or acquired immunodeficiency syndrome (AIDS).

5. History of hemoglobinopathy .

6. Any subject who was currently abusing alcohol or other drugs or had done so within the last 12 months.

7. There are contraindications listed in the acarbose instructions.

8. History of acute or chronic pancreatitis, or current acute or chronic pancreatitis.

9. Type 1 diabetees mellitus.

10. History of diabetic ketoacidosis or hyperosmolar nonketosis coma in recent 1 month.

11. Patients with clinically apparent hepatobiliary disease, including but not limited to chronic active hepatitis and/or severe hepatic insufficiency. Alanine Aminotransferase(ALT) or Aspartate Aminotransferase(AST) > 3x upper limit of normal (ULN), or serum total bilirubin (TB) >34.2 μmol/L (>2 mg/dL).

12. Patients with following renal disease history or renal disease related features:

    1. History of unstable or rapidly progressing renal disease;
    2. Patients with moderate /severe renal impairment or end-stage renal disease (eGFR< 60 mL/min/1.73 m2);
    3. Urinary albumin: creatinine ratio >1800 mg/g;
    4. Serum creatinine (Cr) ≥133 μmol/L (≥1.50 mg/dL) for male subjects; Serum Cr≥124 μmol/L (≥1.40 mg/dL) for female subjects;
    5. Conditions of congenital renal glycosuria.

13. Any of the following cardiovascular diseases within 6 months of the enrollment visit:

    1. Myocardial infarction;
    2. Cardiac surgery or revascularization (coronary artery bypass graft/percutaneous transluminal coronary angioplasty);
    3. Unstable angina;
    4. Congestive heart failure New York Heart Association Class III or IV;
    5. Transient ischemic attack or significant cerebrovascular disease.

14. Any subject , in the judgment of the investigator, was at risk that might affect the interpretation of efficacy or safety data or the conduct ion of the study，including laboratory and physical examination or ECG.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The extent of change in MAGE	8 weeks	Mean absolute glucose excursions (MAGE) was calculated to assess intraday glucose variability. The difference between the consecutive peaks and nadirs exceeding one standard deviation (SD) of the daily mean blood glucose (MBG) level was expressed as absolute glucose excursion (AGE). MAGE was an arithmetic mean of all absolute AGEs.The average MAGE of the last three days of the eighth week are compared with the baseline（The average MAGE of the three days before using acarbose).The extent of change in MAGE is numerical value to to assess glucose variability.

Secondary Outcome Measures

Name	Time	Method
The control rate of HbA1c	12 weeks	When HbA1c\<7% was considered as the criteria, the control rate of HbA1c after 12 weeks.
The extent of change in PPGE,LAGE	8 weeks	Postprandial glucose excursion (PPGE) is calculated as the peak value of glucose after meals minus the glucose level at the beginning of each meal to evaluate the influence of meals on glucose fluctuation.Largest amplitude of glycemic excursions (LAGE) is calculated as the maximum minus the minimum blood glucose levels measured in one day.The average PPGE、LAGE of the last three days of the eighth week compared with the baseline（The average PPGE、LAGE of the three days before using acarbose）.

Trial Locations

Locations (1)

Qilu Hospital of Shandong University; 🇨🇳 Jinan, China