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

Study Overview
=================
Brief 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.

Detailed Description
-----------------
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.

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

Conditions
-----------------
Type I Diabetes

Intervention / Treatment
-----------------
* Drug: Anakinra
* Other: Placebo Comparator


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 8 Years
Maximum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active Treatment<br>14 subjects with receive active treatment with Anakinra. | Drug: Anakinra<br>* Anakinra treatment will be given I.V. as a bolus of 2 mg/kg infused intravenously over 30 minutes followed by infusion of 2 mg/kg/hour for 4 hours.<br>* Other names: anti Interleukin 1 receptor antibodies;|
| Placebo Comparator: Placebo<br>7 subjects will receive the placebo comparator. | Other: Placebo Comparator<br>* A placebo will be given to 7 subjects.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Adverse Events | Type and number of Adverse Events related to anti-IL-1 treatment (anakinra) during the initial 24 hour period of DKA treatment. | 24 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
DKA, Diabetes, Type I Diabetes