Diabetes Mellitus, Type 1
Conditions
Keywords
LADA, saxagliptin, vitamin D3, C-Peptide
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).
Interventions
DRUGSaxagliptin
Take saxagliptin tablet 5mg p.o. qd. for 104 weeks after randomization.
DRUGVitamin D3
Take vitamin D drops 2000 IU p.o. qd. for 104 weeks after randomization.
DRUGInsulin
For optimal control of patients' glucose, researchers can initiate insulin therapy at any time in this trial, choose any brands of insulin after discussion with the patient.
DRUGMetformin
Take Metformin tablet 1.5g p.o. per day for 104 weeks (adjust the dose between 1-1.7g per day according to subject's specific situation) before or after randomization.
Sponsors
Beijing Hospital
The First Affiliated Hospital with Nanjing Medical University
First Affiliated Hospital of Chongqing Medical University
The First Affiliated Hospital of Henan University of Science and Technology
Second Xiangya Hospital of Central South University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Volunteer to participate in the study with informed consent; 2. 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.
Exclusion criteria
1. Pregnancy, breastfeeding or planned pregnancy within two years; 2. Gestational diabetes mellitus or other specific types of diabetes; 3. Allergic to saxagliptin, vitamin D3 and their excipient; 4. Treatment with any anti-diabetic medication other than insulin in the last 8 weeks prior to randomization; 5. Use of systemic corticosteroids therapy (oral, intravenous) continuously for more than 7 days over the past 6 months; 6. Treatment with cytochrome P450 3A4/5 (CYP450 3A4/5) inhibitor; 7. 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; 8. 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; 9. History of malignant tumors; 10. History of mental disorders; 11. History of alcohol abuse or illegal drug abuse; 12. Serious systemic disease which the investigators think would not be suitable for the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
China
Outcome results
None listed