Clinical and Biological Responses to Repeated Administration of Low-dose Interleukin-2 in Patients With Type 1 Diabetes and a Residual Insulin Secretion
Type 1 diabetes (T1D) is caused by the destruction of insulin-producing cells by effector T cells (Teffs), due to a deficiency of regulatory T cells (Tregs). Ciclosporin effectively blocks the Teffs and controls diabetes, but cannot be considered as a long-term treatment. Low-dose interleukin-2 (ld IL-2) activates and expands Tregs in humans. Hence, Ld IL-2 in patients in whom the autoimmune process was blocked early by a short treatment (2 months) of cyclosporine should restore immune homeostasis and maintain some insulin production over the long term.
• • Age at inclusion between ≥ 16 years old (Tanner 5 pubertal stage) and ≤ 45 years old
‣ Type 1 diabetes according to ADA criteria, with at least 1 positive autoantibody among the following: anti-islet, anti-GAD, anti-IA2, anti-ZnT8 and anti-insulin.
⁃ Diagnosis ≤ 3 months
⁃ No acid ketosis
⁃ No weight loss \> 10% OR with fasting C-peptide ≥ 0.1 nmol/L (after a period of ≥ 15 days following the initiation of insulin therapy
⁃ Absence of clinically significant biological abnormalities on hematological, biochemical, hepatic, renal and thyroid tests.
⁃ No documented history of heart disease, no family history of sudden death, AND normal ECG.
⁃ Effective contraception in men and women of childbearing potential \> 2 weeks prior to first administration of the investigational drug and throughout the treatment period (if sexually active). Specifically for women of childbearing age and sexually active, they must use an effective contraceptive method (Pearl Index \< 1). The following methods are acceptable: oral hormonal contraceptives, injectable, or implanted (with the exception of oral minipills: i.e. low doses of gestagens which are not acceptable (lynestrenol and norestisteron), intrauterine contraceptives (e.g. progestin-release systems)),
⁃ Free, informed and written consent, signed by the patient and the investigator, prior to any examination required by the trial.
∙ If the patient is a minor, the signatures of both parents and of the child will be collected (or the legal representative if only one parent is alive).