Protective Effects of Saxagliptin (And Vitamin D3) on β Cell Function in Adult-onset Latent Autoimmune Diabetes

Diabetes Mellitus, Type 1 Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02407899
• Other study ID #: NCRCMD LADA SAX 2015
• Status: Completed
• Phase: Phase 4
• Start date: March 2015
• Est. completion date: December 31, 2020

Study information

• Verified date: April 2021
• Source: Second Xiangya Hospital of Central South University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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) .

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 information / eligibility

• Status: Completed
• Enrollment: 300
• Est. completion date: December 31, 2020
• Est. primary completion date: December 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1

Intervention

Drug:
• Saxagliptin
Take saxagliptin tablet 5mg p.o. qd. for 104 weeks after randomization.
• Vitamin D3
Take vitamin D drops 2000 IU p.o. qd. for 104 weeks after randomization.
• Insulin
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.
• Metformin
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.

Locations

Country	Name	City	State
China	Jilin Province People's Hospital	Changchun	Jilin
China	The Second Hospital of Jilin University	Changchun	Jilin
China	The First People's Hospital of Changde	Changde	Hunan
China	Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University	Changsha	Hunan
China	Affiliated Heji Hospital of Changzhi Medical College	Changzhi	Shanxi
China	Heping Hospital of Changzhi Medical College	Changzhi	Shanxi
China	The First Affiliated Hospital of Chongqing Medical University	Chongqing	Chongqing
China	Dongguan People's Hospital	Dongguan	Guangdong
China	The First Affiliated Hospital of Fujian Medical University	Fujian	Fuzhou
China	Guangdong General Hospital	Guangzhou	Guangdong
China	Guangzhou First People's Hospital	Guangzhou	Guangdong
China	The First Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong
China	Hainan General Hospital	Haikou	Hainan
China	The Second Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Harbin Medical University	Harbin	Heilongjiang
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	First People's Hospital of Yunnan Province	Kunming	Yunnan
China	Gansu Provincial Hospital	Lanzhou	Gansu
China	The First Affiliated Hospital of Henan University of Science and Technology	Luoyang	Henan
China	The First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	The Third Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	Jiangsu Province Hospital	Nanjing	Jiangsu
China	The First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi
China	Beijing Hospital of the Ministry of Health	Peking	Beijing
China	Peking University People's Hospital	Peking	Beijing
China	The Affiliated Hospital of Qingdao University	Qingdao	Shandong
China	Quanzhou First Hospital, Fujian	Quanzhou	Fujian
China	Shanghai Xuhui District Central Hospital	Shanghai	Shanghai
China	The First Hospital of China Medical University	Shenyang	Liaoning
China	Tangshan Gongren Hospital	Tangshan	Hebei
China	Tangshan Gongren Hospital063000	Tangshan	Hebei
China	The Second Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang
China	The First Affiliated Hospital of The Fourth Military Medical University	Xi'an	Shanxi
China	The Northern Jiangsu People's Hospital	Yangzhou	Jiangsu
China	The First People's Hospital of Yueyang	Yueyang	Hunan
China	Henan Provincial People's Hospital	Zhengzhou	Henan

Sponsors (5)

Lead Sponsor	Collaborator
Second Xiangya Hospital of Central South University	Beijing Hospital, First Affiliated Hospital of Chongqing Medical University, The First Affiliated Hospital of Henan University of Science and Technology, The First Affiliated Hospital with Nanjing Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Absolute changes from baseline in Fasting C-peptide levels at week 104.	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.; 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.	From baseline to 104 week
Secondary	Absolute changes from baseline in fasting C-peptide levels and at week 26, 52 and 78.	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.	From baseline to 26, 52, 78 week
Secondary	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.	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.	From baseline to 26, 52, 78, 104 week
Secondary	The proportion of subjects with increased (decreased, unchanged) fasting or post-stimulus C peptide level compared with baseline after 104 weeks of treatment.	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.	From baseline to 104 week
Secondary	The increased percentage of C peptide pre-and post mixed-meal tolerance test (Delta C peptide) after 104 weeks of treatment.	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	From baseline to 104 week
Secondary	Changes of HbA1c levels from baseline and at week 26, 52, 78 and 104.	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.	26, 52, 78, 104 week
Secondary	The proportion of subjects responding to glucose therapy (i.e. HbA1c<7%) after 104 weeks of treatment.	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.	104 week
Secondary	Changes of average daily insulin dose (U/kg/d) from baseline and at week 26, 52, 78 and 104	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.	From baseline to 26, 52, 78, 104 week
Secondary	Changes of GADA titers from baseline and at week 52 and 104.	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.	From baseline to 52, 104 week
Secondary	Absolute changes of body weight and BMI level from baseline and at week 26, 52, 78 and 104.	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.	From baseline to 26, 52, 78, 104 week