Treatment of Presymptomatic (Stage 1) Type 1 Diabetes Pediatric Patients With Treg Cell Preparations and Anti-CD20 Antibody

Exclusion Criteria

• •12. Refusal to participate in the trial or lack of a signed informed consent form
• •13. Suspicion or diagnosis for a type of diabetes other than type 1 diabetes mellitus
• •14. Age under 6 or above 16
• •15. IgA deficiency or history of other diagnosed immunodeficiency (max. 7 infections/year allowed, and the prognosis should indicate that the patient will remain in the study throughout its duration)
• •16. C-peptide levels \< 1.0 ng/ml fasting and in post-stimulation tests increase \< 100%
• •17. Glucose levels in venous blood ≥ 100mg% fasting
• •18. Glucose levels in venous blood after 1 and 2 hours in OGTT ≥ 200mg%
• •19. Glycated hemoglobin level (HbA1c) in venous blood ≥ 5,7%
• •20. BMI \< 25 or \> 75th percentile for a given age or weight of less than 20 kg
• •21. History of hypersensitivity to anti-CD20 or other components of the preparation
• •22. History of hypersensitivity to penicillin and/or streptomycin
• •23. Past or active infection with HBV, HCV, HIV, HTLV I/II, mycobacterium tuberculosis, syphilis. Laboratory evidence of infection without the need for clinical signs and symptoms is sufficient for diagnosis.
• •24. Active infection with the EBV or CMV virus (positive IgM)
• •25. Any fungal, parasitic, viral, or bacterial infection
• •26. History of past or active cancer
• •27. Anemia, lymphopenia, neutropenia, or thrombocytopenia defined as a blood cell count below the lower limit of normal for age found within the last 6 weeks prior to trial inclusion
• •28. Elevated thrombotic activity/history of thrombosis episode
• •29. Any disease prior to inclusion in the trial currently requiring medication for more than 3 months in history
• •30. Diagnosed autoimmune disease other than type 1 diabetes mellitus, including a history of Hashimoto's disease and coeliac disease
• •31. Taking anti-diabetic medication (including insulin) in the last 4 weeks prior to trial inclusion
• •32. History of retinopathy
• •33. History of hypertension
• •34. Current or history of albuminuria
• •35. For women in childbearing potential/menstruating women: pregnancy (from medical interview) or unwillingness to exercise sexual restraint or use effective forms of contraception for the duration of the trial and up to 4 months after completion, if applicable.
• •The following contraceptive methods are acceptable: bilateral fallopian tube closure, sterilization in men, appropriate use of hormonal contraception that inhibits ovulation, hormone-releasing IUDs, and copper IUDs, male or female condoms with spermicide; and cap, uterine disc, or sponge with spermicide.
• •36. Breastfeeding
• •37. For males over 15 years of age: expressed intention to have offspring or donate sperm during the trial or within 4 months after the end of the trial, if applicable
• •38. Excessive anxiety of the participant or his/her legal representatives regarding the procedures used in the trial
• •39. Any medical problem that, in the opinion of the investigator, may adversely affect the participant's health if included in the trial
• •40. Legal representatives and/or children over the age of 15 with an identified alcohol and/or psychoactive substance addiction
• •41. History of disease of unknown etiology
• •42. History of Creutzfeldt-Jacob disease
• •43. History of progressive dementia or degenerative neurological disease, including of unknown origin
• •44. History of taking hormones derived from the human pituitary gland (e.g., growth hormone)
• •45. Treatment with immunosuppressants
• •46. History of corneal, scleral, and dural transplant or undocumented neurosurgery
• •47. History of occurrence of risk factors related to the participant's travel, where there is a possibility of exposure to regional infectious diseases
• •48. Physical signs that indicate the risk of an infectious disease
• •49. History of xenogeneic transplant