A Randomized Controlled, Open-label, Multi-center Study With 104-week Saxagliptin or (and) Vitamin D3 Assessing Protective Effects on Beta Cell Function in Latent Autoimmune Diabetes in Adults (LADA) Treated With Metformin (and Insulin)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 300
- 试验地点
- 39
- 主要终点
- Absolute changes from baseline in Fasting C-peptide levels at week 104.
研究概览
简要总结
The main purpose of this study is to evaluate whether saxagliptin or (and vitamin D3) with metformin (and insulin) therapy can better protect islet β cell function than metformin(and insulin) .
详细描述
LADA is actually a form of type 1 diabetes, which is caused by autoimmune damage of islet β cells and triggered by environmental factors based on genetic susceptibility. LADA shows some characteristics of type 2 diabetes at its onset, which develops slowly and latent, and easily be misdiagnosed as type 2 diabetes due to slowly β cell function deterioration. This is a multi-center, open- label, 1:1:1 randomized controlled trial to investigate the protective effects of saxagliptin and vitamin D3 in LADA patients. The study comprises the 0-6weeks of screening period and the 104-week intervention period. After obtaining the informed consent，the screening will find out the eligible patients according to the inclusion/exclusion criteria, then the patients will be randomized to the 104-week intervention period. Subjects will be randomized into one of the three groups(arms) through central dynamic randomization: metformin (and insulin), metformin(and insulin) +saxagliptin, metformin(and insulin) +saxagliptin+vitamin D3. Our previous randomized- controlled pilot study showed that dipeptidyl peptidase 4 (DPP-4) inhibitors could significantly improve islet β-cell function in patients with LADA. The main purpose of this study: To evaluate whether saxagliptin (and vitamin D3) with metformin (and insulin) therapy can better protect islet β cell function than metformin (and insulin).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Volunteer to participate in the study with informed consent;
- •The LADA patients to be included in this study are defined as:
- •(1) Meet the 1999 WHO Diagnostic Criteria for Diabetes Mellitus; (2) Age at diagnosis of DM ≧ 18 years old; (3) Glutamic acid decarboxylase antibody (GADA) positive; (4) Serum fasting C-peptide ≥ 100 pmol/L or 2-hour postprandial C-peptide≥ 200 pmol/L;
- •Age between 18-70 years old;
- •Diabetes duration <4 year;
- •Outpatient or inpatient.
排除标准
- •Pregnancy, breastfeeding or planned pregnancy within two years;
- •Gestational diabetes mellitus or other specific types of diabetes;
- •Allergic to saxagliptin, vitamin D3 and their excipient;
- •Treatment with any anti-diabetic medication other than insulin in the last 8 weeks prior to randomization;
- •Use of systemic corticosteroids therapy (oral, intravenous) continuously for more than 7 days over the past 6 months;
- •Treatment with cytochrome P450 3A4/5 (CYP450 3A4/5) inhibitor;
- •Alanine aminotransferase (ALT) or aspartate transaminase(AST) more than 3 times of the normal upper limit, total bilirubin (TBIL) more than 2 times of the normal upper limit;
- •Creatinine levels ≧ 1.5 mg/dL(132μmol/L) for males and ≧ 1.4 mg/dL (123μmol/L) for females or creatinine clearance ≦ 50 mL/min;
- •History of malignant tumors;
- •History of mental disorders;
- •History of alcohol abuse or illegal drug abuse;
- •Serious systemic disease which the investigators think would not be suitable for the study.
研究组 & 干预措施
Metformin (and insulin) + saxagliptin
Patients who have diagnosed LADA are assigned to receive Saxagliptin tablets 5mg/d and Metformin 1.5g/d (and insulin at individual dose) for 104-week.
干预措施: Saxagliptin (Drug)
Metformin (and insulin) + saxagliptin
Patients who have diagnosed LADA are assigned to receive Saxagliptin tablets 5mg/d and Metformin 1.5g/d (and insulin at individual dose) for 104-week.
干预措施: Insulin (Drug)
Metformin (and insulin) + saxagliptin
Patients who have diagnosed LADA are assigned to receive Saxagliptin tablets 5mg/d and Metformin 1.5g/d (and insulin at individual dose) for 104-week.
干预措施: Metformin (Drug)
Metformin(insulin)+saxagliptin +vitamin D3
Patients who have diagnosed LADA are assigned to receive Saxagliptin tablets 5 mg/d, vitamin D drop 2000IU/d, Metformin 1.5g/d (and insulin at individual dose) for 104-week.
干预措施: Saxagliptin (Drug)
Metformin(insulin)+saxagliptin +vitamin D3
Patients who have diagnosed LADA are assigned to receive Saxagliptin tablets 5 mg/d, vitamin D drop 2000IU/d, Metformin 1.5g/d (and insulin at individual dose) for 104-week.
干预措施: Vitamin D3 (Drug)
Metformin(insulin)+saxagliptin +vitamin D3
Patients who have diagnosed LADA are assigned to receive Saxagliptin tablets 5 mg/d, vitamin D drop 2000IU/d, Metformin 1.5g/d (and insulin at individual dose) for 104-week.
干预措施: Insulin (Drug)
Metformin(insulin)+saxagliptin +vitamin D3
Patients who have diagnosed LADA are assigned to receive Saxagliptin tablets 5 mg/d, vitamin D drop 2000IU/d, Metformin 1.5g/d (and insulin at individual dose) for 104-week.
干预措施: Metformin (Drug)
Metformin (and insulin)
Patients who have diagnosed LADA are assigned to receive Metformin 1.5g/d(and insulin at individual dose) for 104-week.
干预措施: Insulin (Drug)
Metformin (and insulin)
Patients who have diagnosed LADA are assigned to receive Metformin 1.5g/d(and insulin at individual dose) for 104-week.
干预措施: Metformin (Drug)
结局指标
主要结局
Absolute changes from baseline in Fasting C-peptide levels at week 104.
时间窗: From baseline to 104 week
1. To evaluate the efficacy of saxagliptin plus metformin (and insulin) on beta cell function in LADA patients compared with metformin (and insulin) treatment. By measure absolute changes from baseline in Fasting C-peptide levels at week 104. 2. To evaluate the efficacy of saxagliptin (add on vitamin D) plus metformin (and insulin) on beta cell function in LADA patients compared with metformin (and insulin) treatment.By measure absolute changes from baseline in Fasting C-peptide levels at week 104.
次要结局
- Absolute changes from baseline in C peptide at 60-min and 120-min (AUC) during a mixed-meal tolerance test and at week 26, 52, 78 and 104.(From baseline to 26, 52, 78, 104 week)
- Absolute changes from baseline in fasting C-peptide levels and at week 26, 52 and 78.(From baseline to 26, 52, 78 week)
- The proportion of subjects with increased (decreased, unchanged) fasting or post-stimulus C peptide level compared with baseline after 104 weeks of treatment.(From baseline to 104 week)
- The increased percentage of C peptide pre-and post mixed-meal tolerance test (Delta C peptide) after 104 weeks of treatment.(From baseline to 104 week)
- Changes of HbA1c levels from baseline and at week 26, 52, 78 and 104.(26, 52, 78, 104 week)
- The proportion of subjects responding to glucose therapy (i.e. HbA1c<7%) after 104 weeks of treatment.(104 week)
- Changes of average daily insulin dose (U/kg/d) from baseline and at week 26, 52, 78 and 104(From baseline to 26, 52, 78, 104 week)
- Changes of GADA titers from baseline and at week 52 and 104.(From baseline to 52, 104 week)
- Absolute changes of body weight and BMI level from baseline and at week 26, 52, 78 and 104.(From baseline to 26, 52, 78, 104 week)
研究者
Zhiguang Zhou
Director, Department of Endocrinology, Institute of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Second Xiangya Hospital, Central South University
Second Xiangya Hospital of Central South University