Type 1 diabetes Nutritional, Metabolic, Endocrine Type 1 diabetes mellitus
Conditions
Interventions
Randomization:
The patient receives a sequential number (1 to 45) and is randomized to one of the groups prior to blood collection for expansion according to a predefined bloc of numbe
Sponsors
Gdansk Medical University
Poltreg S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
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
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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 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 3. Daily insulin dose per kg of body weight (DDI) assessed using patient records at 2 years after the first dose of Tregs 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 | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. The following four secondary safety endpoints are documented as AEs of special interest (AESI) and related treatment-emergent AEs (TEAEs), where appropriate, throughout 24 months follow-up: 1.1. Assessment of the occurrence and severity of side effects directly related to Tregs (hypersensitivity reactions, injection-site thromboembolic events) and blood sampling (>2 g/dl drop in hemoglobin levels) 1.2. Assessment of the occurrence and severity of effects directly related to anti-CD20 antibody rituximab administration (hypersensitivity reactions) 1.3. Assessment of the occurrence and severity of side effects associated with administration of Tregs or anti-CD20 rituximab antibodies, primarily immunosuppressive effects: occurrence of infections of any etiology and de novo tumors detected 1.4. Any serious AE (SAE) in two or more patients with a confirmed association with the administration of therapy 2. The efficacy is documented as: 2.1. C-peptide level measured as fasted level from peripheral blood at weeks 2, 5, 12, 26, 39, 52, 65, 78, 92, and 104 2.2. C-peptide level measured post MMTT stimulation and after glucagon test from peripheral blood at weeks 12, 26, 52, 78, and 104 2.3. Exogenous insulin dose per kg of body weight assessed using patient records at weeks 2, 3, 4, 5, 12, 14, 26, 39, 52, 65, 78, 92, and 104 2.4. The proportion of insulin-independent patients (DDI = 0 UI/kg body weight [b.w.]) assessed using patient records at weeks 52 and 104 2.5. The proportion of patients in remission (DDI =0.5 UI/kg b.w. and HbA1c lower than 6.5%) assessed using patient records and laboratory tests at weeks 52 and 104 2.6. HbA1c level (%) measured using patient records and laboratory tests at week 2, 5, 12, 26, 39, 52, 65, 78, 92, and 104 2.7. Glycemic control (fasting average of | — |
Countries
Poland
Outcome results
None listed