Anti-IL-1 Treatment in Children Diabetic Keto-Acidosis (DKA) at Diagnosis of Type 1 Diabetes
- Registration Number
- NCT01477476
- Lead Sponsor
- University of Colorado, Denver
- 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.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
-
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.
-
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Comparator 7 subjects will receive the placebo comparator. Active Treatment Anakinra 14 subjects with receive active treatment with Anakinra.
- Primary Outcome Measures
Name Time Method Frequency of Adverse Events 24 hours Type and number of Adverse Events related to anti-IL-1 treatment (anakinra) during the initial 24 hour period of DKA treatment.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (2)
University of Colorado, Anschutz Medical Campus
🇺🇸Aurora, Colorado, United States
Childrens Hospital Colorado
🇺🇸Aurora, Colorado, United States