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

Sponsor

University of Colorado, Denver (Other)

Overall Status

Withdrawn

CT.gov ID

NCT01477476

Collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)

Enrollment

Locations

Arms

49.7

Actual Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Type I Diabetes	Drug: Anakinra Other: Placebo Comparator	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 1, 2012

Actual Primary Completion Date :

Mar 1, 2016

Actual Study Completion Date :

Apr 22, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Active Treatment 14 subjects with receive active treatment with Anakinra.	Drug: Anakinra 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. Other Names: anti Interleukin 1 receptor antibodies
Placebo Comparator: Placebo 7 subjects will receive the placebo comparator.	Other: Placebo Comparator A placebo will be given to 7 subjects.

Arm

Intervention/Treatment

Active Comparator: Active Treatment

14 subjects with receive active treatment with Anakinra.

Drug: Anakinra

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.

Other Names:

anti Interleukin 1 receptor antibodies

Placebo Comparator: Placebo

7 subjects will receive the placebo comparator.

Other: Placebo Comparator

A placebo will be given to 7 subjects.

Outcome Measures

Primary Outcome Measures

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

8 Years to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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