Anti-IL-1 Treatment in Children DKA at Diagnosis of Type 1 Diabetes

This study is currently recruiting participants.
Verified October 2012 by University of Colorado, Denver
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT01477476
First received: November 18, 2011
Last updated: October 1, 2012
Last verified: October 2012
  Purpose

This is a randomized, double-blind, placebo-controlled phase 2 study. Specific aim is to evaluate feasibility and safety of anti-IL-1 treatment in the course of standard therapy for diabetic ketoacidosis in children and its effect on intracranial pressure.


Condition Intervention Phase
Type I Diabetes
Drug: Anakinra
Other: Placebo Comparator
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Anti-IL-1 Treatment in Children DKA at Diagnosis of Type 1 Diabetes.

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • Anakinra [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
    Type and number of AE of anti-IL-1 treatment (anakinra) during the initial 24 h period of DKA treatment.


Estimated Enrollment: 21
Study Start Date: March 2012
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Active Treatment
14 subjects with recieve 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 Name: 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.
Other Name: Placebo Comparator

Detailed Description:

Anakinra is a fully human IL-1ra, 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 in T2D28,29 and a randomized trial of anakinra in recent onset T1D is underway in Europe 25. 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 with 2:1 allocation (14 active treatment vs. 7 placebo). 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 36,37) immediately after confirmation of the diagnosis of DKA and when laboratory safety parameters are available (CBC and pregnancy test) and after a consent is obtained. Primary outcomes: Safety and tolerability of anti-IL-1 treatment (anakinra) during the initial 24 h 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

Ages Eligible for Study:   8 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 8-18 years at diagnosis of type 1 diabetes
  • Diabetic ketoacidosis: 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01477476

Contacts
Contact: Arleta Rewers, MD, Phd 303-725-2576 arleta.rewers@childrenscolorado.org

Locations
United States, Colorado
University of Colorado, Anschutz Medical Campus Recruiting
Aurora, Colorado, United States, 80045
Contact: Arleta Rewers, MD, PhD    303-724-2576    arleta.rewers@childrenscolorado.org   
Childrens Hospital Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Arleta Rewers, MD, PhD    303-724-2576      
Sponsors and Collaborators
University of Colorado, Denver
Investigators
Principal Investigator: Arleta Rewers, MD, Phd University of Colorado, Denver
  More Information

Publications:
Donath, M. Y., Weder, C., and Brunner, A. XOMA 052, a potential disease modifying anti-ILbeta antibody, shows sustained HbA1c reductions 3 months after a single injection with no increases in safety parameters in subjects with type 2 diabetes. Diabetes 58[Suppl. 1], A30. 2009. Ref Type: Abstract
Rewers, A Klingensmith G Brown A Rewers M. Children presenting in DKA at diagnosis have higher HbA1cduring initial 8 years of type 1 diabetes independently of access to care and ethnicity. Pediatric Diabetes 8[Suppl. 7], 32. 2007. Ref Type: Abstract

Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT01477476     History of Changes
Other Study ID Numbers: 11-0814, P30DK057516
Study First Received: November 18, 2011
Last Updated: October 1, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Colorado, Denver:
DKA
Diabetes
Type I Diabetes

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Interleukin 1 Receptor Antagonist Protein
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 20, 2014