Immune Intervention With Rituximab to Preserve Beta Cell Function in Early Onset Type 1 Diabetes

Study Overview
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Brief Summary
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Transient elimination of B lymphocytes with anti-CD20 monoclonal antibody would decrease immune-mediated destruction of beta cells and result in preserved beta-cell function in patients with type 1 diabetes of recent onset.

Detailed Description
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Although the presence of autoantibodies is a diagnostic criterion, the immunopathogenesis of beta-cell destruction in type 1 diabetes is typically associated with T-lymphocyte autoimmunity. Many T-lymphocyte-mediated diseases include a B-lymphocyte component. B lymphocytes can play a crucial role as antigen-presenting cells, expressing high levels of class II major-histocompatibility-complex antigens and generating cryptic peptides to which T lymphocytes are not tolerant. B lymphocytes can be selectively depleted with the anti-CD20 monoclonal antibody. We will test the hypothesis that transient elimination of B lymphocytes with anti-CD20 monoclonal antibody would decrease immune-mediated destruction of beta cells and result in preserved beta-cell function in patients with type 1 diabetes of recent onset.

Official Title
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Immune Intervention With Anti-CD20 Monoclonal Antibody to Preserve Beta Cell Function in Early Onset Type 1 Diabetes

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Drug: rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of type 1 diabetes The age of subjects between 8 and 70 years old Course of disease within 12 months Presence of at least one type of detectable islet autoantibody [zinc transporter 8 antibody(ZnT8A),glutamic acid decarboxylase antibody(GADA),protein tyrosine phosphatase-2 antibody(IA-2A),insulin autoantibody(IAA)] Fasting C-peptide levels of at least 0.2 pmol/mL Exclusion Criteria: Confirmed diagnosis of type 2 diabetes Severe chronic or acute complications of diabetes Severe infection or damage to the immune response Presence of chronic latent infection in vivo Viral hepatitis B patients whose hepatitis B virus(HBV)DNA > log10^5 Liver and kidney dysfunction, alanine aminotransferase(ALT), aspartate aminotransferase(AST), and creatinine more than 2 times the upper limit of normal Hypotension, systolic blood pressure(SBP) ≤ 90mmHg, diastolic blood pressure(DBP) ≤ 60mmHg Patients with rheumatoid arthritis Allergic to any component of this drug Pregnancy, breast-feeding women Use of other immunosuppressive agents 3 months before selected

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rituximab<br>patients who had newly diagnosed type 1 diabetes are assigned to receive infusions of rituximab of 125mg/m^2 day1 day8 day15 day22 repeat after six months (only day1 and day8) besides insulin | Drug: rituximab<br>* anti-CD20 monoclonal antibody 125mg/m^2 day1 day8 day15 day22 repeat after six months (only day1 and day8)<br>* Other names: anti-CD20 monoclonal antibody;|
| No Intervention: parallel control<br>patients who had newly diagnosed type 1 diabetes only use insulin | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of 3-hour Mean Area Under the Curve (AUC) of C-peptide | Change of 3-hour mean area under the curve (AUC) of C-peptide at 6 months from baseline. AUC was calculated from C-peptide timing measurements during the 3-hour mixed meal tolerance test with the trapezoidal rule. The mean AUC for C-peptide is equal to the calculated AUC divided by the 3 h interval (i.e., AUC/180). All mean C-peptide AUC data were transformed as log (mean AUC) for analysis. | 6 months after participants completed the injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Fasting C-peptide | The change of fasting level of C-peptide during the 3-hour of a mixed meal tolerance test at 6 months from baseline. All fasting C-peptide data were transformed as log (fasting C-peptide) for analysis. | 6 months after participants completed the injection | 
| Change of Peak C-peptide | The change of peak level of C-peptide during the 3-hour of a mixed meal tolerance test at 6 months from baseline. All peak C-peptide data were transformed as log (peak C-peptide) for analysis. | 6 months after participants completed the injection | 
| HbA1c Levels | Glycated hemoglobin (HbA1c) levels (%) | 6 months after participants completed the injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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age, type 1 diabetes, course of disease, autoantibodies, C-peptide levels