Clinical trial NCT01280682: Immune Intervention With Rituximab to Preserve Beta Cell Function in Early Onset Type 1 Diabetes
Official title: Immune Intervention With Anti-CD20 Monoclonal Antibody to Preserve Beta Cell Function in Early Onset Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 1 Diabetes
Keywords: type 1 diabetes
age
course of disease
autoantibodies
C-peptide levels
Lead sponsor: Nanjing Medical University
Sponsor class: OTHER
First posted: 2011-01-21
Enrollment: 120
Sex: ALL
Minimum age (years): 8
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change of 3-hour Mean Area Under the Curve (AUC) of C-peptide
timeFrame: 6 months after participants completed the injection
Secondary outcomes:
measure: Change of Fasting C-peptide
timeFrame: 6 months after participants completed the injection
measure: Change of Peak C-peptide
timeFrame: 6 months after participants completed the injection
measure: HbA1c Levels
timeFrame: 6 months after participants completed the injection
Other outcomes:
Locations:
city: Nanjing
country: China
facility: First Affiliated Hospital, Nanjing Medical University
state: Jiangsu
Study officials:
affiliation: First Affiliated Hospital, Nanjing Medical University, China
name: Tao Yang, MD/PhD
role: PRINCIPAL_INVESTIGATOR
References: