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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

Tracking Information
First Submitted Date  ICMJE November 12, 2014
First Posted Date  ICMJE December 4, 2014
Last Update Posted Date July 6, 2016
Study Start Date  ICMJE November 2014
Estimated Primary Completion Date March 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 1, 2014)
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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 1, 2014)
  • 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 ]
  • 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 ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Effect of Saxagliptin on Glucose Fluctuation and Immune Regulation in Patients With Type 1 Diabetes
Official Title  ICMJE The Effect of Saxagliptin on Glucose Fluctuation and Immune Regulation in Patients With Type 1 Diabetes
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Type 1 Diabetes
Intervention  ICMJE
  • 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.
Study Arms  ICMJE
  • Experimental: insulin+Saxagliptin
    Patients who have diagnosed type 1 diabetes are assigned to receive Saxagliptin tablets 5 mg and insulin for 24-week.
    Interventions:
    • Drug: Saxagliptin
    • Drug: Insulin
  • Active Comparator: insulin
    Patients who have diagnosed type 1 diabetes only use insulin.
    Intervention: Drug: Insulin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: December 1, 2014)
184
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2017
Estimated Primary Completion Date March 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years to 65 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02307695
Other Study ID Numbers  ICMJE 2014-SR-123
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Yang Tao, Nanjing Medical University
Study Sponsor  ICMJE Nanjing Medical University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Tao Yang, MD/PhD First Affiliated Hospital, Nanjing Medical University, China
PRS Account Nanjing Medical University
Verification Date July 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP