Type 1 DiabetesPhase 4NCT01280682
Immune Intervention With Rituximab to Preserve Beta Cell Function in Early Onset Type 1 Diabetes
A Phase 4 study testing rituximab in people with Type 1 Diabetes, run by Yang Tao at 1 site in China.
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. Read more about this study
- Who is it for?
- Ages 8 to 70 years
- Conditions the study is for
- Type 1 Diabetes
- What is being tested?
- rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteChina
- Study dates
- Jul 2010to Dec 2018
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
China1 site
First Affiliated Hospital, Nanjing Medical University
Nanjing, Jiangsu, 210029
About this study
Official title: 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.
Read the 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.
- Conditions
- Type 1 Diabetes
- Being tested
- rituximab
- Keywords
- type 1 diabetes, age, course of disease, autoantibodies, C-peptide levels
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rituximabDrug
Also called anti-CD20 monoclonal antibody
anti-CD20 monoclonal antibody 125mg/m^2 day1 day8 day15 day22 repeat after six months (only day1 and day8)
| Study group | Role | What they receive |
|---|---|---|
| rituximab | Experimental | 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 Receives: Drug: rituximab |
| parallel control | No intervention | patients who had newly diagnosed type 1 diabetes only use insulin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months after participants completed the injection
Secondary outcomes (3)
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.
Measured: 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.
Measured: 6 months after participants completed the injection
HbA1c Levels
Glycated hemoglobin (HbA1c) levels (%)
Measured: 6 months after participants completed the injection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jan 2011 (estimated)
- Study startJul 2010
- Primary completionDec 2016
- Study completionDec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Type 1 DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yang Tao
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Yang Tao, Nanjing Medical University
- Investigators
- Tao Yang, MD/PhD, Principal investigator, First Affiliated Hospital, Nanjing Medical University, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01280682
- Sponsor's protocol ID
- 2010-SR-021
- Status last verified
- Mar 2023
- First submitted
- 29 Jul 2010
- Last updated
- 11 Dec 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Ajmal N, Bogart MC, Khan P, Max-Harry IM, Healy AM, Nunemaker CS. Identifying Promising Immunomodulators for Type 1 Diabetes (T1D) and Islet Transplantation. J Diabetes Res. 2024 Dec 20;2024:5151171. doi: 10.1155/jdr/5151171. eCollection 2024.
PubMed 39735417Su Z, Ma C, Zhao R, Jiang Y, Cai Y, Yong G, Yang T, Xu X. Heterogeneity of circulating CXCR5-PD-1hiTph cells in patients of type 2 and type 1 diabetes in Chinese population. Acta Diabetol. 2023 Jun;60(6):767-776. doi: 10.1007/s00592-023-02055-6. Epub 2023 Mar 6.
PubMed 36879107
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immune Intervention With Anti-CD20 Monoclonal Antibody to Preserve Beta Cell Function in Early Onset Type 1 Diabetes
- ClinicalTrials.gov ID
- NCT01280682
- Acronym / sponsor ID
- 2010-SR-021
- Conditions
- Type 1 Diabetes
- Keywords
- type 1 diabetes, age, course of disease, autoantibodies, C-peptide levels
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- Yang TaoUniversity, hospital or other
- Study start
- Jul 2010 (actual)
- Primary completion
- Dec 2016 (actual)
- Study completion
- Dec 2018 (actual)
- First posted
- 21 Jan 2011 (estimated)
- Results
- Posted 11 Dec 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| rituximab | Experimental | Drug: rituximabpatients 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 |
| parallel control | No intervention | –patients who had newly diagnosed type 1 diabetes only use insulin |
Who may qualify
- Ages
- 8 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rituximabAlso: anti-CD20 monoclonal antibodyanti-CD20 monoclonal antibody 125mg/m^2 day1 day8 day15 day22 repeat after six months (only day1 and day8) | Drug | rituximab |
Primary outcome
Change of 3-hour Mean Area Under the Curve (AUC) of C-peptide
Time frame: 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.
3 secondary outcomes
Change of Fasting C-peptide
Time frame: 6 months after participants completed the injection
Change of Peak C-peptide
Time frame: 6 months after participants completed the injection
HbA1c Levels
Time frame: 6 months after participants completed the injection
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39735417Ajmal N, Bogart MC, Khan P, Max-Harry IM, Healy AM, Nunemaker CS. Identifying Promising Immunomodulators for Type 1 Diabetes (T1D) and Islet Transplantation. J Diabetes Res. 2024 Dec 20;2024:5151171. doi: 10.1155/jdr/5151171. eCollection 2024.
- Derived from this study: PubMed 36879107Su Z, Ma C, Zhao R, Jiang Y, Cai Y, Yong G, Yang T, Xu X. Heterogeneity of circulating CXCR5-PD-1hiTph cells in patients of type 2 and type 1 diabetes in Chinese population. Acta Diabetol. 2023 Jun;60(6):767-776. doi: 10.1007/s00592-023-02055-6. Epub 2023 Mar 6.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tao Yang, MD/PhD principal investigator
First Affiliated Hospital, Nanjing Medical University, China
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing rituximab in people with Type 1 Diabetes, run by Yang Tao at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of 3-hour Mean Area Under the Curve (AUC) of C-peptide (time frame: 6 months after participants completed the injection). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01280682, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Dec 2023.