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

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

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 Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Drug: rituximab

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 Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Tao Yang, MD/PhD; Phone Number: 6466 86-25-83718836; Email: yangt@njmu.edu.cn

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • First Affiliated Hospital, Nanjing Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 43 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: rituximab; anti-CD20 monoclonal antibody 125mg/m^2 day1 day8 day15 day22 repeat after six months (only day1 and day8); Other Names: anti-CD20 monoclonal antibody
No Intervention: parallel control; patients who had newly diagnosed type 1 diabetes only use insulin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
HbA1c Levels	Glycated hemoglobin (HbA1c) levels (%)	6 months after participants completed the injection

Collaborators and Investigators

• Sponsor: Yang Tao
• Investigators: Principal Investigator: Tao Yang, MD/PhD, First Affiliated Hospital, Nanjing Medical University, China

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2010
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: July 29, 2010
• First Submitted That Met QC Criteria: January 19, 2011
• First Posted (Estimated): January 21, 2011

Study Record Updates

• Last Update Posted (Estimated): December 11, 2023
• Last Update Submitted That Met QC Criteria: March 9, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: age; type 1 diabetes; autoantibodies; course of disease; C-peptide levels
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: 2010-SR-021