Therapy of type 1 diabetes with T regulatory cells and anti-CD20 monoclonal antibody

Phase 1

Completed

• Conditions: Type 1 diabetes; Nutritional, Metabolic, Endocrine; Type 1 diabetes mellitus

• Registration Number: ISRCTN37116985
• Lead Sponsor: Gdansk Medical University

Brief Summary

2022 Abstract results in https://doi.org/10.1111/dom.14723 (added 21/04/2022)

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Completion: 2019-12-31
• Study Start: 2021-01-22
• Last Update Posted: 16 May 2022

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

1. 8 to 16 years of age
2. BMI in the range of 25-75 percentiles (according to OLAF)
3. Fasting plasma C-peptide more than 0.7 ng/ml and in a stimulation test the increase is =100%
4. The presence of anti-islet autoantibody (ICA, IAA, GAD) - high titer one of the antibodies (=4 times the norm, not applicable ICA) or low titer of two or three antibodies (2-4 times the norm)
5. Ability to provide written informed consent by parents (and patients if above 16 years old)
6. Involvement of the patients and parents in the intensive diabetes management defined as self-monitoring of glucose values no less than three times per day and by the administration of insulin
7. Appropriate venous access for blood drawing

Exclusion Criteria

1. No agreement for participation in the study and no informed consent signed
2. Other than autoimmune type 1 diabetes
3. Age below 8 and above 16 years
4. IgA deficiency or other genetic defect present
5. BMI <25 or >75 percentiles for a particular age
6. Hypersensitivity to anti-CD20 or other components of the preparation
7. Presence or history of active infection including hepatitis B, hepatitis C, HIV, tuberculosis (TB) or syphilis. Subjects with laboratory evidence of active infection are excluded even in the absence of clinical evidence of active infection
8. Presence of active EBV virus infection (positive IgM)
9. Presence or history of active systemic fungal infection
10. Any history of malignancy
11. Anemia, lymphopenia, neutropenia or thrombocytopenia below the lower limits of the reference range during the 6 weeks before study
12. Known hypercoagulative state
13. Medical treatment requiring chronic use of drugs other than insulin longer than 3 months
14. Treatment with any anti-diabetic medication other than insulin within 4 weeks of enrolment
15. Diabetic retinopathy
16. Arterial hypertension
17. Presence or history of macroalbuminuria
18. For female subjects older than 15 years positive pregnancy test, unwillingness to use effective contraceptive measures for the duration of the study and 4 months after discontinuation, when appropriate
19. For male subjects: intent to procreate during the duration of the study or within 4 months after discontinuation when appropriate
20. Excessive anxiety of the patient or parents related to the procedures
21. Any medical condition that, in the opinion of the investigator, will interfere with safe participation in the trial
22. For parents and children older than 15 years: known active alcohol or substance abuse

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br> 1. Number of adverse effects assessed from histories taken from patients, obtained during physical examination and laboratory tests at 2 years (week 104) after the first dose of Tregs<br> 2. C-peptide level measured as fasted, post-MMTT stimulation and after glucagon test from peripheral blood at 2 years after the first dose of Tregs<br> 3. Daily insulin dose per kg of body weight (DDI) assessed using patient records at 2 years after the first dose of Tregs<br> 4. Number of treated patients in remission (the number of patients with daily insulin dose lower than 0.5U/kg/day and HbA1c lower than 6.5%) at 1 and 2 years after the first dose of Tregs<br>