Protective Effects of Saxagliptin (And Vitamin D3) on β Cell Function in Adult-onset Latent Autoimmune Diabetes
- Conditions
- Diabetes Mellitus, Type 1
- Interventions
- Registration Number
- NCT02407899
- Lead Sponsor
- Second Xiangya Hospital of Central South University
- Brief Summary
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) .
- Detailed Description
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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 300
- 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; 3. Age between 18-70 years old; 4. Diabetes duration <4 year; 5. Outpatient or inpatient.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Metformin (and insulin) + saxagliptin Insulin 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. Metformin(insulin)+saxagliptin +vitamin D3 Insulin 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. Metformin (and insulin) Insulin Patients who have diagnosed LADA are assigned to receive Metformin 1.5g/d(and insulin at individual dose) for 104-week. Metformin (and insulin) + saxagliptin 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. Metformin (and insulin) + saxagliptin Metformin 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. Metformin(insulin)+saxagliptin +vitamin D3 Saxagliptin 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. Metformin(insulin)+saxagliptin +vitamin D3 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. Metformin(insulin)+saxagliptin +vitamin D3 Metformin 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. Metformin (and insulin) Metformin Patients who have diagnosed LADA are assigned to receive Metformin 1.5g/d(and insulin at individual dose) for 104-week.
- Primary Outcome Measures
Name Time Method Absolute changes from baseline in Fasting C-peptide levels at week 104. 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.
- Secondary Outcome Measures
Name Time Method 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 To evaluate the efficacy of saxagliptin (add on vitamin D) plus metformin (and insulin) on indicators of beta cell function compared with LADA patients treated with metformin (and insulin). By measure 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.
Absolute changes from baseline in fasting C-peptide levels and at week 26, 52 and 78. From baseline to 26, 52, 78 week To evaluate the efficacy of saxagliptin (add on vitamin D) plus metformin (and insulin) on indicators of beta cell function compared with LADA patients treated with metformin (and insulin). By measure absolute changes from baseline in fasting C-peptide levels and at week 26, 52 and 78.
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 To evaluate the efficacy of saxagliptin (add on vitamin D) plus metformin (and insulin) on indicators of beta cell function compared with LADA patients treated with metformin (and insulin). By measure the proportion of subjects with increased (decreased, unchanged) fasting or post-stimulus C peptide level compared with baseline after 104 weeks of treatment.
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 To evaluate the efficacy of saxagliptin (add on vitamin D) plus metformin (and insulin) on indicators of beta cell function compared with LADA patients treated with metformin (and insulin). By measure the increased percentage of C peptide pre-and post mixed-meal tolerance test (Delta C peptide) after 104 weeks of treatment
Changes of HbA1c levels from baseline and at week 26, 52, 78 and 104. 26, 52, 78, 104 week To evaluate the efficacy of saxagliptin (add on vitamin D) plus metformin (and insulin) on glycemic control compared with LADA patients treated with metformin (and insulin). By measure Changes of HbA1c levels from baseline and at week 26, 52, 78 and 104.
The proportion of subjects responding to glucose therapy (i.e. HbA1c<7%) after 104 weeks of treatment. 104 week To evaluate the efficacy of saxagliptin (add on vitamin D) plus metformin (and insulin) on glycemic control compared with LADA patients treated with metformin (and insulin). By measure the proportion of subjects responding to glucose therapy (i.e. HbA1c\<7%) after 104 weeks of treatment.
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 To evaluate the efficacy of saxagliptin (add on vitamin D) plus metformin (and insulin) on glycemic control /insulin-sparing compared with LADA patients treated with metformin (and insulin). By measure Changes of average daily insulin dose (U/kg/d) from baseline and at week 26, 52, 78 and 104.
Changes of GADA titers from baseline and at week 52 and 104. From baseline to 52, 104 week To evaluate the efficacy of saxagliptin (add on vitamin D) plus metformin (and insulin) on glycemic control /insulin-sparing/changes of autoantibody titer compared with LADA patients treated with metformin (and insulin). By measure changes of GADA titers from baseline and at week 52 and 104.
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 To evaluate the efficacy of saxagliptin (add on vitamin D) plus metformin (and insulin) on body weight/BMI level compared with LADA patients treated with metformin (and insulin). By measure Changes of BMI from baseline and at week 26, 52, 78 and 104.
Trial Locations
- Locations (39)
Gansu Provincial Hospital
🇨🇳Lanzhou, Gansu, China
Guangdong General Hospital
🇨🇳Guangzhou, Guangdong, China
Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University
🇨🇳Changsha, Hunan, China
Guangzhou First People's Hospital
🇨🇳Guangzhou, Guangdong, China
The First Affiliated Hospital of Henan University of Science and Technology
🇨🇳Luoyang, Henan, China
The First People's Hospital of Yueyang
🇨🇳Yueyang, Hunan, China
The Third Affiliated Hospital of Nanchang University
🇨🇳Nanchang, Jiangxi, China
Jiangsu Province Hospital
🇨🇳Nanjing, Jiangsu, China
The First Hospital of China Medical University
🇨🇳Shenyang, Liaoning, China
The Affiliated Hospital of Qingdao University
🇨🇳Qingdao, Shandong, China
The First Affiliated Hospital of Fujian Medical University
🇨🇳Fujian, Fuzhou, China
Dongguan People's Hospital
🇨🇳Dongguan, Guangdong, China
Hainan General Hospital
🇨🇳Haikou, Hainan, China
The First Affiliated Hospital of Guangxi Medical University
🇨🇳Nanning, Guangxi, China
The First People's Hospital of Changde
🇨🇳Changde, Hunan, China
Jilin Province People's Hospital
🇨🇳Changchun, Jilin, China
Affiliated Heji Hospital of Changzhi Medical College
🇨🇳Changzhi, Shanxi, China
The First Affiliated Hospital of The Fourth Military Medical University
🇨🇳Xi'an, Shanxi, China
The First Affiliated Hospital of Chongqing Medical University
🇨🇳Chongqing, Chongqing, China
Quanzhou First Hospital, Fujian
🇨🇳Quanzhou, Fujian, China
Peking University People's Hospital
🇨🇳Peking, Beijing, China
Beijing Hospital of the Ministry of Health
🇨🇳Peking, Beijing, China
The First Affiliated Hospital of Guangzhou Medical University
🇨🇳Guangzhou, Guangdong, China
Tangshan Gongren Hospital063000
🇨🇳Tangshan, Hebei, China
Tangshan Gongren Hospital
🇨🇳Tangshan, Hebei, China
Harbin Medical University
🇨🇳Harbin, Heilongjiang, China
Henan Provincial People's Hospital
🇨🇳Zhengzhou, Henan, China
The First Affiliated Hospital of South China University
🇨🇳Hengyang, Hunan, China
The Second Hospital University of South China
🇨🇳Hengyang, Hunan, China
The Affiliated Hospital of Inner Mongolia Medical University
🇨🇳Hohhot, Inner Mongolia, China
The First People's Hospital of Huaihua
🇨🇳Huaihua, Hunan, China
The Northern Jiangsu People's Hospital
🇨🇳Yangzhou, Jiangsu, China
The Second Hospital of Jilin University
🇨🇳Changchun, Jilin, China
The First Affiliated Hospital of Nanchang University
🇨🇳Nanchang, Jiangxi, China
Heping Hospital of Changzhi Medical College
🇨🇳Changzhi, Shanxi, China
Shanghai Xuhui District Central Hospital
🇨🇳Shanghai, Shanghai, China
The Second Affiliated Hospital of Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
The Second Affiliated Hospital of Wenzhou Medical University
🇨🇳Wenzhou, Zhejiang, China
First People's Hospital of Yunnan Province
🇨🇳Kunming, Yunnan, China