Anti-IL-1 Treatment in Children Diabetic Keto-Acidosis (DKA) at Diagnosis of Type 1 Diabetes
Anti-IL-1 Treatment in Children Diabetic Keto-Acidosis (DKA) at Diagnosis of Type 1 Diabetes
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.
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