Type 1 Diabetes
Conditions
Keywords
type 1 diabetes, age, course of disease, autoantibodies, C-peptide levels
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.
Interventions
DRUGrituximab
anti-CD20 monoclonal antibody 125mg/m\^2 day1 day8 day15 day22 repeat after six months (only day1 and day8)
Sponsors
Yang Tao
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
8 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 (%) |
Countries
China
Participant flow
Recruitment details
patients who had newly diagnosed type 1 diabetes
Pre-assignment details
patients whose C-peptide were too low
Participants by arm
| Arm | Count |
|---|---|
| Rituximab patients who had newly diagnosed type 1 diabetes are assigned to receive infusions of rituximab besides insulin | 77 |
| Parallel Control patients who had newly diagnosed type 1 diabetes only used insulin | 30 |
| Total | 107 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 6 |
| Overall Study | Withdrawal by Subject | 0 | 7 |
Baseline characteristics
| Characteristic | Parallel Control | Rituximab | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 17 Participants | 51 Participants | 68 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 26 Participants | 39 Participants |
| Age, Continuous | 20.08 years STANDARD_DEVIATION 7.4 | 17.81 years STANDARD_DEVIATION 8.76 | 18.27 years STANDARD_DEVIATION 8.51 |
| Region of Enrollment China | 30 participants | 77 participants | 107 participants |
| Sex: Female, Male Female | 14 Participants | 32 Participants | 46 Participants |
| Sex: Female, Male Male | 16 Participants | 45 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 77 | 0 / 30 |
| other Total, other adverse events | 44 / 77 | 0 / 30 |
| serious Total, serious adverse events | 0 / 77 | 0 / 30 |
Outcome results
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.
Time frame: 6 months after participants completed the injection
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rituximab | Change of 3-hour Mean Area Under the Curve (AUC) of C-peptide | -0.01 pmol/L | Standard Error 0.03 |
| Parallel Control | Change of 3-hour Mean Area Under the Curve (AUC) of C-peptide | -0.35 pmol/L | Standard Error 0.05 |
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.
Time frame: 6 months after participants completed the injection
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rituximab | Change of Fasting C-peptide | -0.03 pmol/L | Standard Error 0.04 |
| Parallel Control | Change of Fasting C-peptide | -0.34 pmol/L | Standard Error 0.07 |
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.
Time frame: 6 months after participants completed the injection
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rituximab | Change of Peak C-peptide | -0.01 pmol/L | Standard Error 0.03 |
| Parallel Control | Change of Peak C-peptide | -0.29 pmol/L | Standard Error 0.06 |
Secondary
HbA1c Levels
Glycated hemoglobin (HbA1c) levels (%)
Time frame: 6 months after participants completed the injection
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Rituximab | HbA1c Levels | 6.84 percentage of hemoglobin |
| Parallel Control | HbA1c Levels | 9.35 percentage of hemoglobin |