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Trial record 80 of 330 for:    C-peptide | "Diabetes Mellitus, Insulin-Dependent"

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
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

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).

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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


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




Primary Outcome Measures :
  1. 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 :
  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.



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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:

  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.

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

  Show 39 Study Locations
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

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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     History of Changes
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, Type 1
Diabetes Mellitus
Latent Autoimmune Diabetes in Adults
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin
Insulin, Globin Zinc
Metformin
Saxagliptin
Vitamins
Vitamin D
Ergocalciferols
Cholecalciferol
Dipeptidyl-Peptidase IV Inhibitors
Hypoglycemic Agents
Physiological Effects of Drugs
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