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

Type 1 Diabetes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01280682
• Other study ID #: 2010-SR-021
• Status: Completed
• Phase: Phase 4
• Start date: July 2010
• Est. completion date: December 2018

Study information

• Verified date: March 2023
• Source: Nanjing Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: December 2018
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes

Intervention

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

Locations

Country	Name	City	State
China	First Affiliated Hospital, Nanjing Medical University	Nanjing	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Yang Tao

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	HbA1c Levels	Glycated hemoglobin (HbA1c) levels (%)	6 months after participants completed the injection