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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 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: July 2, 2014
Last verified: July 2014
  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 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 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Childrens Hospital Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Arleta Rewers, MD, PhD    303-724-2576      
University of Colorado, Anschutz Medical Campus Recruiting
Aurora, Colorado, United States, 80045
Contact: Arleta Rewers, MD, PhD    303-724-2576    arleta.rewers@childrenscolorado.org   
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
Galea J, Ogungbenro K, Hulme S et al. Intravenous anakinra can achieve experimentally effective concentrations in the central nervous system within a therapeutic time window: results of a dose-ranging study. J Cereb Blood Flow Metab. 2010.

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: July 2, 2014
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
Autoimmune Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases

ClinicalTrials.gov processed this record on November 25, 2014