Protective Effects of Saxagliptin (And Vitamin D3) on β Cell Function in Adult-onset Latent Autoimmune Diabetes
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)
1 other identifier
interventional
300
1 country
39
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) .
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4
Started Mar 2015
Longer than P75 for phase_4
39 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 1, 2015
CompletedFirst Submitted
Initial submission to the registry
March 31, 2015
CompletedFirst Posted
Study publicly available on registry
April 3, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 30, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
December 31, 2020
CompletedApril 20, 2021
April 1, 2021
5.8 years
March 31, 2015
April 18, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Absolute changes from baseline in Fasting C-peptide levels at week 104.
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.
From baseline to 104 week
Secondary Outcomes (9)
Absolute changes from baseline in fasting C-peptide levels and at week 26, 52 and 78.
From baseline to 26, 52, 78 week
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
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
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
Changes of HbA1c levels from baseline and at week 26, 52, 78 and 104.
26, 52, 78, 104 week
- +4 more secondary outcomes
Study Arms (3)
Metformin (and insulin) + saxagliptin
EXPERIMENTALPatients 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
EXPERIMENTALPatients 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)
ACTIVE COMPARATORPatients who have diagnosed LADA are assigned to receive Metformin 1.5g/d(and insulin at individual dose) for 104-week.
Interventions
Take saxagliptin tablet 5mg p.o. qd. for 104 weeks after randomization.
Take vitamin D drops 2000 IU p.o. qd. for 104 weeks after randomization.
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.
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.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Second Xiangya Hospital of Central South Universitylead
- Beijing Hospitalcollaborator
- The First Affiliated Hospital with Nanjing Medical Universitycollaborator
- First Affiliated Hospital of Chongqing Medical Universitycollaborator
- The First Affiliated Hospital of Henan University of Science and Technologycollaborator
Study Sites (39)
Peking University People's Hospital
Beijing, Beijing Municipality, 100044, China
Beijing Hospital of the Ministry of Health
Beijing, Beijing Municipality, 100730, China
The First Affiliated Hospital of Chongqing Medical University
Chongqing, Chongqing Municipality, 400042, China
Quanzhou First Hospital, Fujian
Quanzhou, Fujian, 350005, China
The First Affiliated Hospital of Fujian Medical University
Fujian, Fuzhou, 350005, China
Gansu Provincial Hospital
Lanzhou, Gansu, 730000, China
Dongguan People's Hospital
Dongguan, Guangdong, 523059, China
Guangdong General Hospital
Guangzhou, Guangdong, 510080, China
Guangzhou First People's Hospital
Guangzhou, Guangdong, 510120, China
The First Affiliated Hospital of Guangzhou Medical University
Guangzhou, Guangdong, 510120, China
The First Affiliated Hospital of Guangxi Medical University
Nanning, Guangxi, 530021, China
Hainan General Hospital
Haikou, Hainan, 570311, China
Tangshan Gongren Hospital063000
Tangshan, Hebei, 063000, China
Tangshan Gongren Hospital
Tangshan, Hebei, 063000, China
Harbin Medical University
Harbin, Heilongjiang, 150081, China
The First Affiliated Hospital of Henan University of Science and Technology
Luoyang, Henan, 471023, China
Henan Provincial People's Hospital
Zhengzhou, Henan, 450003, China
The First People's Hospital of Changde
Changde, Hunan, 415003, China
Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University
Changsha, Hunan, 410011, China
The First Affiliated Hospital of South China University
Hengyang, Hunan, 421001, China
The Second Hospital University of South China
Hengyang, Hunan, 421001, China
The First People's Hospital of Huaihua
Huaihua, Hunan, 418000, China
The First People's Hospital of Yueyang
Yueyang, Hunan, 414000, China
The Affiliated Hospital of Inner Mongolia Medical University
Hohhot, Inner Mongolia, 010050, China
Jiangsu Province Hospital
Nanjing, Jiangsu, 210029, China
The Northern Jiangsu People's Hospital
Yangzhou, Jiangsu, 225001, China
The First Affiliated Hospital of Nanchang University
Nanchang, Jiangxi, 330006, China
The Third Affiliated Hospital of Nanchang University
Nanchang, Jiangxi, 330008, China
The Second Hospital of Jilin University
Changchun, Jilin, 130000, China
Jilin Province People's Hospital
Changchun, Jilin, 130021, China
The First Hospital of China Medical University
Shenyang, Liaoning, 110122, China
The Affiliated Hospital of Qingdao University
Qingdao, Shandong, 266000, China
Shanghai Xuhui District Central Hospital
Shanghai, Shanghai Municipality, 200031, China
Heping Hospital of Changzhi Medical College
Changzhi, Shanxi, 046000, China
Affiliated Heji Hospital of Changzhi Medical College
Changzhi, Shanxi, 140400, China
The First Affiliated Hospital of The Fourth Military Medical University
Xi’an, Shanxi, 710032, China
First People's Hospital of Yunnan Province
Kunming, Yunnan, 650032, China
The Second Affiliated Hospital of Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310009, China
The Second Affiliated Hospital of Wenzhou Medical University
Wenzhou, Zhejiang, 325000, China
Related Publications (1)
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.
PMID: 37076476DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Zhiguang Zhou, MD/PhD
Second Xiangya Hospital of Central South University
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Director, Department of Endocrinology, Institute of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Second Xiangya Hospital, Central South University
Study Record Dates
First Submitted
March 31, 2015
First Posted
April 3, 2015
Study Start
March 1, 2015
Primary Completion
December 30, 2020
Study Completion
December 31, 2020
Last Updated
April 20, 2021
Record last verified: 2021-04