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

April 18, 2021 updated by: Zhiguang Zhou, Second Xiangya Hospital of Central South University

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)

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) .

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
300

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 Names:
  • 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 Names:
  • 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: 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 Names:
  • 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 Names:
  • Metformin Hydrochloride tablet
Drug: Vitamin D3
Take vitamin D drops 2000 IU p.o. qd. for 104 weeks after randomization.
Other Names:
  • Cholecalciferol
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 Names:
  • 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 Names:
  • Metformin Hydrochloride tablet

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
From baseline to 104 week

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
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.
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.
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.
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.
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.
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
From baseline to 104 week
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.
26, 52, 78, 104 week
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.
104 week
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.
From baseline to 26, 52, 78, 104 week
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.
From baseline to 52, 104 week
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.
From baseline to 26, 52, 78, 104 week

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Second Xiangya Hospital of Central South University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
The First Affiliated Hospital with Nanjing Medical University
Beijing Hospital
The First Affiliated Hospital of Henan University of Science and Technology
First Affiliated Hospital of Chongqing Medical University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2015

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 30, 2020

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 31, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 31, 2015

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 3, 2015

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 20, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 18, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NCRCMD LADA SAX 2015

Drug and device information, study documents

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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