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

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ClinicalTrials.gov Identifier: NCT02407899

Recruitment Status : Recruiting

First Posted : April 3, 2015

Last Update Posted : August 13, 2019

See Contacts and Locations

Sponsor:

Collaborators:

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

Information provided by (Responsible Party):

Zhiguang Zhou, Second Xiangya Hospital of Central South University

Study Description

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) .

Condition or disease	Intervention/treatment	Phase
Diabetes Mellitus, Type 1	Drug: Saxagliptin Drug: Vitamin D3 Drug: Insulin Drug: Metformin	Phase 4

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).

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	300 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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 Start Date :	March 2015
Estimated Primary Completion Date :	December 2020
Estimated Study Completion Date :	June 2021

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Type 1 diabetes

MedlinePlus related topics: Vitamin D

Drug Information available for: Cholecalciferol Metformin Metformin hydrochloride Vitamin D Insulin Insulin human Saxagliptin

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	Drug: Saxagliptin Take saxagliptin tablet 5mg p.o. qd. for 104 weeks after randomization. Other Names: Onglyza Dipeptidyl peptidase 4 (DPP-4) inhibitor 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. Other Name: Recombinant Human Insulin, Insulin analogue. 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. Other Name: Metformin Hydrochloride tablet
Experimental: 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.	Drug: Saxagliptin Take saxagliptin tablet 5mg p.o. qd. for 104 weeks after randomization. Other Names: Onglyza Dipeptidyl peptidase 4 (DPP-4) inhibitor Drug: Vitamin D3 Take vitamin D drops 2000 IU p.o. qd. for 104 weeks after randomization. Other Name: Cholecalciferol 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. Other Name: Recombinant Human Insulin, Insulin analogue. 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. Other Name: Metformin Hydrochloride tablet
Active Comparator: Metformin (and insulin) Patients who have diagnosed LADA are assigned to receive Metformin 1.5g/d(and insulin at individual dose) for 104-week.	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. Other Name: Recombinant Human Insulin, Insulin analogue. 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. Other Name: Metformin Hydrochloride tablet

Outcome Measures

Primary Outcome Measures :

Absolute changes from baseline in Fasting C-peptide levels at week 104. [ Time Frame: 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 Outcome Measures :

Absolute changes from baseline in fasting C-peptide levels and at week 26, 52 and 78. [ Time Frame: 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.
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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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.
The proportion of subjects responding to glucose therapy (i.e. HbA1c<7%) after 104 weeks of treatment. [ Time Frame: 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.
Changes of average daily insulin dose (U/kg/d) from baseline and at week 26, 52, 78 and 104 [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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.

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 70 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02407899

Contacts

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Contact: Zhiguang Zhou, MD/PhD	86-731-85292154	zhouzg@hotmail.com

Locations

Show 39 study locations

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China, Beijing
Peking University People's Hospital	Recruiting
Peking, Beijing, China, 100044
Beijing Hospital of the Ministry of Health	Recruiting
Peking, Beijing, China, 100730
China, Chongqing
The First Affiliated Hospital of Chongqing Medical University	Recruiting
Chongqing, Chongqing, China, 400042
China, Fujian
Quanzhou First Hospital, Fujian	Recruiting
Quanzhou, Fujian, China, 350005
China, Fuzhou
The First Affiliated Hospital of Fujian Medical University	Recruiting
Fujian, Fuzhou, China, 350005
China, Gansu
Gansu Provincial Hospital	Recruiting
Lanzhou, Gansu, China, 730000
China, Guangdong
Dongguan People's Hospital	Recruiting
Dongguan, Guangdong, China, 523059
Guangdong General Hospital	Recruiting
Guangzhou, Guangdong, China, 510080
Guangzhou First People's Hospital	Recruiting
Guangzhou, Guangdong, China, 510120
The First Affiliated Hospital of Guangzhou Medical University	Recruiting
Guangzhou, Guangdong, China, 510120
China, Guangxi
The First Affiliated Hospital of Guangxi Medical University	Recruiting
Nanning, Guangxi, China, 530021
China, Hainan
Hainan General Hospital	Recruiting
Haikou, Hainan, China, 570311
China, Hebei
Tangshan Gongren Hospital063000	Recruiting
Tangshan, Hebei, China, 063000
Tangshan Gongren Hospital	Recruiting
Tangshan, Hebei, China, 063000
China, Heilongjiang
Harbin Medical University	Recruiting
Harbin, Heilongjiang, China, 150081
China, Henan
The First Affiliated Hospital of Henan University of Science and Technology	Recruiting
Luoyang, Henan, China, 471023
Henan Provincial People's Hospital	Recruiting
Zhengzhou, Henan, China, 450003
China, Hunan
The First People's Hospital of Changde	Recruiting
Changde, Hunan, China, 415003
Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University	Recruiting
Changsha, Hunan, China, 410011
Contact: Zhiguang Zhou, MD/PhD 86-731-85292154 zhouzg@hotmail.com
The First Affiliated Hospital of South China University	Recruiting
Hengyang, Hunan, China, 421001
The Second Hospital University of South China	Recruiting
Hengyang, Hunan, China, 421001
The First People's Hospital of Huaihua	Recruiting
Huaihua, Hunan, China, 418000
The First People's Hospital of Yueyang	Recruiting
Yueyang, Hunan, China, 414000
China, Inner Mongolia
The Affiliated Hospital of Inner Mongolia Medical University	Recruiting
Hohhot, Inner Mongolia, China, 010050
China, Jiangsu
Jiangsu Province Hospital	Recruiting
Nanjing, Jiangsu, China, 210029
The Northern Jiangsu People's Hospital	Recruiting
Yangzhou, Jiangsu, China, 225001
China, Jiangxi
The First Affiliated Hospital of Nanchang University	Recruiting
Nanchang, Jiangxi, China, 330006
The Third Affiliated Hospital of Nanchang University	Recruiting
Nanchang, Jiangxi, China, 330008
China, Jilin
The Second Hospital of Jilin University	Recruiting
Changchun, Jilin, China, 130000
Jilin Province People's Hospital	Recruiting
Changchun, Jilin, China, 130021
China, Liaoning
The First Hospital of China Medical University	Recruiting
Shenyang, Liaoning, China, 110122
China, Shandong
The Affiliated Hospital of Qingdao University	Recruiting
Qingdao, Shandong, China, 266000
China, Shanghai
Shanghai Xuhui District Central Hospital	Recruiting
Shanghai, Shanghai, China, 200031
China, Shanxi
Heping Hospital of Changzhi Medical College	Recruiting
Changzhi, Shanxi, China, 046000
Affiliated Heji Hospital of Changzhi Medical College	Recruiting
Changzhi, Shanxi, China, 140400
The First Affiliated Hospital of The Fourth Military Medical University	Recruiting
Xi'an, Shanxi, China, 710032
China, Yunnan
First People's Hospital of Yunnan Province	Recruiting
Kunming, Yunnan, China, 650032
China, Zhejiang
The Second Affiliated Hospital of Zhejiang University School of Medicine	Recruiting
Hangzhou, Zhejiang, China, 310009
The Second Affiliated Hospital of Wenzhou Medical University	Recruiting
Wenzhou, Zhejiang, China, 325000

Sponsors and Collaborators

Second Xiangya Hospital of Central South University

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

Investigators

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Principal Investigator:	Zhiguang Zhou, MD/PhD	Second Xiangya Hospital of Central South University

More Information

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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, Second Xiangya Hospital of Central South University
ClinicalTrials.gov Identifier:	NCT02407899
Other Study ID Numbers:	NCRCMD LADA SAX 2015
First Posted:	April 3, 2015 Key Record Dates
Last Update Posted:	August 13, 2019
Last Verified:	August 2019

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Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by Zhiguang Zhou, Second Xiangya Hospital of Central South University:


LADA saxagliptin vitamin D3 C-Peptide

Additional relevant MeSH terms:

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Diabetes Mellitus Diabetes Mellitus, Type 1 Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Autoimmune Diseases Immune System Diseases Vitamin D Cholecalciferol Insulin Insulin, Globin Zinc Metformin Saxagliptin Dipeptidyl-Peptidase IV Inhibitors	Hypoglycemic Agents Physiological Effects of Drugs Vitamins Micronutrients Nutrients Growth Substances Bone Density Conservation Agents Calcium-Regulating Hormones and Agents Incretins Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action

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