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

Phase 4

Completed

• Conditions: Type 1 Diabetes
• Interventions: Drug: rituximab

• Registration Number: NCT01280682
• Lead Sponsor: Yang Tao

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.

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Study Start: 2010-07
• Study First Submitted: 2010-07-29
• Study First Submitted QC: 2011-01-19
• Study First Posted: 2011-01-21
• Results First Submitted: 2012-10-16
• Primary Completion: 2016-12
• Study Completion: 2018-12
• Status Verified: 2023-03
• Results First Submitted QC: 2023-03-09
• Last Update Submitted: 2023-03-09
• Results First Posted: 2023-12-11
• Last Update Posted: 2023-12-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 120

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
rituximab	rituximab	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

Primary Outcome Measures

Name	Time	Method
Change of 3-hour Mean Area Under the Curve (AUC) of C-peptide	6 months after participants completed the injection	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.

Secondary Outcome Measures

Name	Time	Method
Change of Fasting C-peptide	6 months after participants completed the injection	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.
Change of Peak C-peptide	6 months after participants completed the injection	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.
HbA1c Levels	6 months after participants completed the injection	Glycated hemoglobin (HbA1c) levels (%)

Trial Locations

Locations (1)

First Affiliated Hospital, Nanjing Medical University; 🇨🇳 Nanjing, Jiangsu, China