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

Sponsor

Nanjing Medical University (Other)

Overall Status

Unknown status

CT.gov ID

NCT01280682

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 1	Drug: rituximab	Phase 4

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jul 1, 2010

Anticipated Primary Completion Date :

Dec 1, 2012

Anticipated Study Completion Date :

Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: rituximab	Drug: rituximab anti-CD20 monoclonal antibody 125mg/m^2 day1 day8 day15 day22 repeat after six months (only day1 and day8)

Arm

Intervention/Treatment

Experimental: rituximab

Drug: rituximab

anti-CD20 monoclonal antibody 125mg/m^2 day1 day8 day15 day22 repeat after six months (only day1 and day8)

Outcome Measures

Primary Outcome Measures

CD19+ cells [1 week later]
number of CD19+ cells

Secondary Outcome Measures

C-peptide level [6 monthes later]
C-peptide level during the first 2 hours of a mixed meal tolerance test
glycated hemoglobin level [6 monthes later]
insulin dose [6 monthes later]
insulin dose(u/Kg)

Eligibility Criteria

Criteria

Ages Eligible for Study:

8 Years to 45 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Confirmed diagnosis of type 1 diabetes
The age of subjects between 8 and 45 years old
Course of disease within 1 year
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)]
Stimulated peak 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