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

Yang Tao

Status and phase: Completed; Phase 4

Conditions: Type 1 Diabetes

Treatments: Drug: rituximab

Study type: Interventional

Funder types: Other

Identifiers

NCT01280682

2010-SR-021

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 120 patients

Sex: All

Ages: 8 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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120 participants in 2 patient groups

rituximab

Experimental group

Description:

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

Treatment:

Drug: rituximab

parallel control

No Intervention group

Description:

patients who had newly diagnosed type 1 diabetes only use insulin