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Trial record 3 of 3271 for:    Type 1 Diabetes

The Effect of Saxagliptin on Glucose Fluctuation and Immune Regulation in Patients With Type 1 Diabetes

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ClinicalTrials.gov Identifier: NCT02307695
Recruitment Status : Unknown
Verified July 2016 by Yang Tao, Nanjing Medical University.
Recruitment status was:  Recruiting
First Posted : December 4, 2014
Last Update Posted : July 6, 2016
Sponsor:
Information provided by (Responsible Party):
Yang Tao, Nanjing Medical University

Brief Summary:
To investigate whether saxagliptin could reduce the fluctuation of glycemia and improve the glycemic control in those type 1 diabetes through mechanisms of suppressing glucagon secretion, improving beta cell function, and re-regulating of the T cell immune system.

Condition or disease Intervention/treatment Phase
Type 1 Diabetes Drug: Saxagliptin Drug: Insulin Phase 4

Detailed Description:

Type 1 diabetes mellitus (T1DM) is characterized by immune mediated beta-cell destruction. Due to the imbalance between glucagon and insulin, long-term T1DM patients experience frequent hypoglycaemia and high glucose variability despite of multiple daily injections of insulin.

Dipeptidyl peptidase 4 (DPP-4) inhibitors are a new class of anti-diabetic agents and are widely used in clinical practice to improve glycemic control and protect β-cell function in patients with type 2 diabetes mellitus(T2DM). Saxagliptin, a DPP-4 inhibitor, improves glycemic control in patients with T2DM by increasing endogenous active, intact glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide in response to food, which augments insulin secretion and decreases glucagon release. This mechanism can lead to the reduction of glucose variation. In some pilot studies, incretin-based therapy in patients with T1DM can improve glucose control and reduce hypoglycemia, the mechanism probably is that it regulates glucagon level. In type 1 diabetic mouse models, DPP-4 inhibitors preserves beta-cell mass and stimulating beta-cell replication.

Interestingly, DPP-4 is also known as cluster of differentiation antigen 26(CD26).It is expressed on the membrane of many types of lymphocyte, e.g. T, B and natural killer(NK)cells, and is involved in their cellular functions. CD26 plays a key role in many aspects in lymphocyte function beyond its DPP-4 enzymatic activity.These observations make it a promising therapeutic target.

Recently, the attention of saxagliptin has been mainly focused on type 2 diabetes, data in type 1 diabetes is rare. We are going to carry out this phase 4 study to testify our hypothesis that saxagliptin could reduce the fluctuation of glycemia and improve the glycemic control in those type 1 diabetes through mechanisms of suppressing glucagon secretion, improving beta cell function, and re-regulating of the T cell immune system.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 184 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Effect of Saxagliptin on Glucose Fluctuation and Immune Regulation in Patients With Type 1 Diabetes
Study Start Date : November 2014
Estimated Primary Completion Date : March 2017
Estimated Study Completion Date : March 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1

Arm Intervention/treatment
Experimental: insulin+Saxagliptin
Patients who have diagnosed type 1 diabetes are assigned to receive Saxagliptin tablets 5 mg and insulin for 24-week.
Drug: Saxagliptin
saxagliptin 5 mg p.o. qd, 24 week
Other Names:
  • Onglyza
  • DPP-IV inhibitor

Drug: Insulin
Patients will be treated according to routine clinical practice at the discretion of the treating physician.

Active Comparator: insulin
Patients who have diagnosed type 1 diabetes only use insulin.
Drug: Insulin
Patients will be treated according to routine clinical practice at the discretion of the treating physician.




Primary Outcome Measures :
  1. Change of Mean amplitude of glycemic excursions (MAGE) from baseline in patients with type 1 diabetes treated with saxagliptin plus insulin or insulin alone by continuous glucose monitoring system (CGMS) [ Time Frame: 24 week ]

Secondary Outcome Measures :
  1. Change of C-peptide area under the curve (AUC C-peptide) or fasting C-peptide from baseline in patients with type 1 diabetes treated with saxagliptin plus insulin or insulin alone by 3-hour mixed meal tolerance test(MMTT) [ Time Frame: 24 week ]
  2. Change of Haemoglobin A1c (HbA1c) from baseline in patients with type 1 diabetes treated with saxagliptin plus insulin or insulin alone [ Time Frame: 24 week ]
  3. Change of insulin dosage (U/kg/d) from baseline in patients with type 1 diabetes treated with saxagliptin plus insulin or insulin alone [ Time Frame: 24 week ]


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Ages Eligible for Study:   12 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Provision of informed consent prior to any study specific procedures;
  2. Diagnosed with type 1 diabetes;
  3. Men or women who are 12 to 65 years of age at time of consenting upon Visit 1.;
  4. Positivity for at least one of the four islet autoantibodies(IA-2A、IAA、GADA、ZnT8A);
  5. 6.5% ≤ HbA1c ≤10.0%.

Exclusion Criteria:

  1. type 2 diabetes;
  2. Evidence of chronic or acute complications of diabetes which is unstable and requires hospitalization;
  3. Evidence of disease stress;
  4. History of administration of any antihyperglycemic therapy (other than insulin) during the 12 weeks prior to Visit 1;
  5. Have a history of, or currently have, acute or chronic pancreatitis;
  6. Immunocompromised individuals such as patients that have undergone organ transplantation or patients diagnosed with HIV or patients with agranulocytosis;
  7. Evidence of chronic or acute infection;
  8. Active liver disease and/or significant abnormal liver function defined as Aspartate transaminase(AST) ≥3x Upper Limit of Normal(ULN) and/or Alanine aminotransferase (ALT) ≥3x Upper Limit of Normal(ULN);
  9. History of unstable or rapidly progressing renal disease, creatinine clearance(CrCl) ≤50ml/min;
  10. Congestive heart failure defined as New York Heart Association (NYHA) class III or IV and/or left ventricular ejection fraction of ≤ 40%;
  11. Rheumatoid arthritis or other autoimmune disease(except AITD);
  12. Hypersensitivity to saxagliptin;
  13. History of drug allergy or allergic disease
  14. History of alcohol abuse, illegal drug abuse, mental disease or other disease which is not eligible for the study
  15. Pregnant or breastfeeding patients;
  16. Patients with any diseases which in the judgement of the investigator would compromise the patient's safety or successful participation in the clinical study
  17. Any condition where, in the opinion of the investigator, participation in this study may pose a significant risk to the patient or could render the patient unable to successfully complete the study
  18. Any disease or condition which the investigator feels would interfere with the trial;
  19. Treatment with other immunosuppressive agent such as systemic glucocorticoids other than replacement therapy. Inhaled, local injected and topical use of glucocorticoids is allowed during the last 90 days prior to Visit 1;
  20. Participation in a clinical study during the last 90 days prior to Visit 1;
  21. Patients who are participating in other clinical study;
  22. Treatment with strong cytochrome P450 3A4/5 (CYP3A4/5) inhibitors or other contraindications to therapy as outlined in the saxagliptin package insert;
  23. History of haemoglobinopathies (sickle cell anaemia or thalassemias, sideroblastic anaemia).

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): NCT02307695


Contacts
Contact: Tao Yang, MD/PhD 86-25-83718836 ext 6466 yangt@njmu.edu.cn

Locations
China, Jiangsu
First Affiliated Hospital, Nanjing Medical University Recruiting
Nanjing, Jiangsu, China, 210029
Contact: Tao Yang, PhD    86-25-83718836 ext 6466    yangt@njmu.edu.cn   
Principal Investigator: Tao Yang, PhD         
Sponsors and Collaborators
Nanjing Medical University
Investigators
Principal Investigator: Tao Yang, MD/PhD First Affiliated Hospital, Nanjing Medical University, China

Responsible Party: Yang Tao, Department of Endocrinology & Metabolism, Nanjing Medical University
ClinicalTrials.gov Identifier: NCT02307695     History of Changes
Other Study ID Numbers: 2014-SR-123
First Posted: December 4, 2014    Key Record Dates
Last Update Posted: July 6, 2016
Last Verified: July 2016

Keywords provided by Yang Tao, Nanjing Medical University:
Saxagliptin
Type 1 Diabetes
Glycemic variability
C-Peptide

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin, Globin Zinc
Saxagliptin
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action