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

NCT ID: NCT02407899

Last Updated: 2021-04-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-31
• Study Completion Date: 2020-12-31

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).

Conditions

Diabetes Mellitus, Type 1

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Saxagliptin

Intervention Type: DRUG

Take saxagliptin tablet 5mg p.o. qd. for 104 weeks after randomization.

Insulin

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Saxagliptin

Intervention Type: DRUG

Take saxagliptin tablet 5mg p.o. qd. for 104 weeks after randomization.

Vitamin D3

Intervention Type: DRUG

Take vitamin D drops 2000 IU p.o. qd. for 104 weeks after randomization.

Insulin

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Metformin (and insulin)

Patients who have diagnosed LADA are assigned to receive Metformin 1.5g/d(and insulin at individual dose) for 104-week.

Group Type: ACTIVE_COMPARATOR

Insulin

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Interventions

Saxagliptin

Take saxagliptin tablet 5mg p.o. qd. for 104 weeks after randomization.

Intervention Type: DRUG

Vitamin D3

Take vitamin D drops 2000 IU p.o. qd. for 104 weeks after randomization.

Intervention Type: DRUG

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Other Intervention Names

Onglyza; Dipeptidyl peptidase 4 (DPP-4) inhibitor; Cholecalciferol; Recombinant Human Insulin, Insulin analogue.; Metformin Hydrochloride tablet

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing Hospital

OTHER_GOV

Sponsor Role: collaborator

The First Affiliated Hospital with Nanjing Medical University

OTHER

Sponsor Role: collaborator

First Affiliated Hospital of Chongqing Medical University

OTHER

Sponsor Role: collaborator

The First Affiliated Hospital of Henan University of Science and Technology

OTHER

Sponsor Role: collaborator

Second Xiangya Hospital of Central South University

OTHER

Sponsor Role: lead

Responsible Party

Zhiguang Zhou

Director, Department of Endocrinology, Institute of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Second Xiangya Hospital, Central South University

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zhiguang Zhou, MD/PhD

Role: PRINCIPAL_INVESTIGATOR

Second Xiangya Hospital of Central South University

Locations

Peking University People's Hospital

Beijing, Beijing Municipality, China

Beijing Hospital of the Ministry of Health

Beijing, Beijing Municipality, China

The First Affiliated Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, China

Quanzhou First Hospital, Fujian

Quanzhou, Fujian, China

The First Affiliated Hospital of Fujian Medical University

Fujian, Fuzhou, China

Gansu Provincial Hospital

Lanzhou, Gansu, China

Dongguan People's Hospital

Dongguan, Guangdong, 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

The First Affiliated Hospital of Guangxi Medical University

Nanning, Guangxi, China

Hainan General Hospital

Haikou, Hainan, China

Tangshan Gongren Hospital063000

Tangshan, Hebei, China

Tangshan Gongren Hospital

Tangshan, Hebei, China

Harbin Medical University

Harbin, Heilongjiang, China

The First Affiliated Hospital of Henan University of Science and Technology

Luoyang, Henan, China

Henan Provincial People's Hospital

Zhengzhou, Henan, 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

The First Affiliated Hospital of South China University

Hengyang, Hunan, China

The Second Hospital University of South China

Hengyang, Hunan, China

The First People's Hospital of Huaihua

Huaihua, Hunan, China

The First People's Hospital of Yueyang

Yueyang, Hunan, China

The Affiliated Hospital of Inner Mongolia Medical University

Hohhot, Inner Mongolia, China

Jiangsu Province Hospital

Nanjing, Jiangsu, China

The Northern Jiangsu People's Hospital

Yangzhou, Jiangsu, China

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

The Third Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

The Second Hospital of Jilin University

Changchun, Jilin, China

Jilin Province People's Hospital

Changchun, Jilin, China

The First Hospital of China Medical University

Shenyang, Liaoning, China

The Affiliated Hospital of Qingdao University

Qingdao, Shandong, China

Shanghai Xuhui District Central Hospital

Shanghai, Shanghai Municipality, China

Heping Hospital of Changzhi Medical College

Changzhi, Shanxi, 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

First People's Hospital of Yunnan Province

Kunming, Yunnan, 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

Countries

China

References

Yan X, Li X, Liu B, Huang J, Xiang Y, Hu Y, Tang X, Zhang Z, Huang G, Xie Z, Zhou H, Liu Z, Wang X, Leslie RD, Zhou Z. Combination therapy with saxagliptin and vitamin D for the preservation of beta-cell function in adult-onset type 1 diabetes: a multi-center, randomized, controlled trial. Signal Transduct Target Ther. 2023 Apr 20;8(1):158. doi: 10.1038/s41392-023-01369-9.

Reference Type: DERIVED

PMID: 37076476 (View on PubMed)

Other Identifiers

NCRCMD LADA SAX 2015

Identifier Type: -

Identifier Source: org_study_id