anti-il-1 treatment in children diabetic keto-acidosis (dka) at diagnosis of type 1 diabetes

Conditions: Type I Diabetes

Summary: this is a randomized, double-blind, placebo-controlled phase 2 study. specific aim is to evaluate feasibility and safety of anti-il-1 (interleukin 1) treatment in the course of standard therapy for diabetic ketoacidosis in children and its effect on intracranial pressure.

anakinra is a fully human il-1ra (interleukin 1 receptor agonist) licensed in 2001 by fda for the treatment of rheumatoid arthritis. it competitively binds to the il-1 receptor, thus blocking il-1 signaling. it is a short-acting agent that requires daily subcutaneous administration at 1-2 mg/kg, maximum 100 mg/dose. it has been effective in lowering hba1c (glycated haemoglobin) in t2d (type 2 diabetes) and a randomized trial of anakinra in recent onset t1d (type 1 diabetes) is underway in europe. overall, anakinra has been used in adults and children with a good safety record, for more than 10 years. infrequent side effects include infections, neutropenia, nausea, diarrhea, cardiopulmonary arrest, influenza-like symptoms, and production of anti-anakinra antibodies. study design: a double-blinded placebo-controlled rct (randomized controlled trial) with 2:1 allocation (14 active treatment vs. 7 placebo). anakinra treatment will be given as a bolus of 2 mg/kg infused intravenously over 30 minutes followed by infusion of 2 mg/kg/hour for 4 hours immediately after confirmation of the diagnosis of dka (diabetic keto-acidosis) and when laboratory safety parameters are available (cbc (complete blood count) and pregnancy test) and after a consent is obtained. primary outcomes: safety and tolerability of anti-il-1 treatment (anakinra) during the initial 24 hr period of dka treatment. secondary outcomes: optic nerve sheath diameter (cut-off to define cerebral edema: 4.5 mm); changes in cytokines levels during the treatment with anakinra.

Eligibility criteria:
inclusion criteria: * age 8-18 years at diagnosis of type 1 diabetes * diabetic ketoacidosis with: * plasma glucose concentration \>300 mg/dl, * venous ph \<7.30 or * serum bicarbonate concentration \<15 mmol/l, and * ketones in urine or serum * hematology: * wbc \>3000 x 109/l; * platelets \>100,000 x 109/l; * hemoglobin \>10.0 g/dl * negative blood pregnancy test in females. exclusion criteria: * children with underlying disorders, including: * active autoimmune or immune deficiency disorder other than type 1 diabetes, * malignancy, * organ transplant, * any condition requiring chronic corticosteroid use * previous immunotherapy to prevent type 1 diabetes * current or prior infection with hiv, hepatitis b or hepatitis c assessed by history * patients who present with dka concomitant with alcohol or drug use, * head trauma, * meningitis or other conditions which might affect neurological function * renal failure * any condition, medical or otherwise that would, in the opinion of the investigator, prevent complete participation in the study, or that would pose a significant hazard to the subject's participation * patients with a history of known hypersensitivity to: * e coli-derived proteins, * anakinra, or * any components of the investigational drug product

Keywords: dka diabetes type i diabetes