Clinical trial NCT02407899: Protective Effects of Saxagliptin (And Vitamin D3) on β Cell Function in Adult-onset Latent Autoimmune Diabetes
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 1
Keywords: LADA
saxagliptin
vitamin D3
C-Peptide
Lead sponsor: Second Xiangya Hospital of Central South University
Sponsor class: OTHER
Collaborators: name: Beijing Hospital
name: The First Affiliated Hospital with Nanjing Medical University
name: First Affiliated Hospital of Chongqing Medical University
name: The First Affiliated Hospital of Henan University of Science and Technology
First posted: 2015-04-03
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Absolute changes from baseline in Fasting C-peptide levels at week 104.
timeFrame: From baseline to 104 week
Secondary outcomes:
measure: Absolute changes from baseline in fasting C-peptide levels and at week 26, 52 and 78.
timeFrame: From baseline to 26, 52, 78 week
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.
timeFrame: From baseline to 26, 52, 78, 104 week
measure: The proportion of subjects with increased (decreased, unchanged) fasting or post-stimulus C peptide level compared with baseline after 104 weeks of treatment.
timeFrame: From baseline to 104 week
measure: The increased percentage of C peptide pre-and post mixed-meal tolerance test (Delta C peptide) after 104 weeks of treatment.
timeFrame: From baseline to 104 week
measure: Changes of HbA1c levels from baseline and at week 26, 52, 78 and 104.
timeFrame: 26, 52, 78, 104 week
measure: The proportion of subjects responding to glucose therapy (i.e. HbA1c<7%) after 104 weeks of treatment.
timeFrame: 104 week
measure: Changes of average daily insulin dose (U/kg/d) from baseline and at week 26, 52, 78 and 104
timeFrame: From baseline to 26, 52, 78, 104 week
measure: Changes of GADA titers from baseline and at week 52 and 104.
timeFrame: From baseline to 52, 104 week
measure: Absolute changes of body weight and BMI level from baseline and at week 26, 52, 78 and 104.
timeFrame: From baseline to 26, 52, 78, 104 week
Other outcomes:
Locations:
city: Peking
country: China
facility: Peking University People's Hospital
state: Beijing
city: Peking
country: China
facility: Beijing Hospital of the Ministry of Health
state: Beijing
city: Chongqing
country: China
facility: The First Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Quanzhou
country: China
facility: Quanzhou First Hospital, Fujian
state: Fujian
city: Fujian
country: China
facility: The First Affiliated Hospital of Fujian Medical University
state: Fuzhou
city: Lanzhou
country: China
facility: Gansu Provincial Hospital
state: Gansu
city: Dongguan
country: China
facility: Dongguan People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong General Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Guangzhou First People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Nanning
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Haikou
country: China
facility: Hainan General Hospital
state: Hainan
city: Tangshan
country: China
facility: Tangshan Gongren Hospital063000
state: Hebei
city: Tangshan
country: China
facility: Tangshan Gongren Hospital
state: Hebei
city: Harbin
country: China
facility: Harbin Medical University
state: Heilongjiang
city: Luoyang
country: China
facility: The First Affiliated Hospital of Henan University of Science and Technology
state: Henan
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
state: Henan
city: Changde
country: China
facility: The First People's Hospital of Changde
state: Hunan
city: Changsha
country: China
facility: Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University
state: Hunan
city: Hengyang
country: China
facility: The First Affiliated Hospital of South China University
state: Hunan
city: Hengyang
country: China
facility: The Second Hospital University of South China
state: Hunan
city: Huaihua
country: China
facility: The First People's Hospital of Huaihua
state: Hunan
city: Yueyang
country: China
facility: The First People's Hospital of Yueyang
state: Hunan
city: Hohhot
country: China
facility: The Affiliated Hospital of Inner Mongolia Medical University
state: Inner Mongolia
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Yangzhou
country: China
facility: The Northern Jiangsu People's Hospital
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Nanchang
country: China
facility: The Third Affiliated Hospital of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: The Second Hospital of Jilin University
state: Jilin
city: Changchun
country: China
facility: Jilin Province People's Hospital
state: Jilin
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
state: Shandong
city: Shanghai
country: China
facility: Shanghai Xuhui District Central Hospital
state: Shanghai
city: Changzhi
country: China
facility: Heping Hospital of Changzhi Medical College
state: Shanxi
city: Changzhi
country: China
facility: Affiliated Heji Hospital of Changzhi Medical College
state: Shanxi
city: Xi'an
country: China
facility: The First Affiliated Hospital of The Fourth Military Medical University
state: Shanxi
city: Kunming
country: China
facility: First People's Hospital of Yunnan Province
state: Yunnan
city: Hangzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University School of Medicine
state: Zhejiang
city: Wenzhou
country: China
facility: The Second Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
Study officials:
affiliation: Second Xiangya Hospital of Central South University
name: Zhiguang Zhou, MD/PhD
role: PRINCIPAL_INVESTIGATOR
References: