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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2016 by University of Colorado, Denver
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
University of Colorado, Denver Identifier:
First received: November 18, 2011
Last updated: April 20, 2016
Last verified: April 2016
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 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 Diabetic Keto-Acidosis (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:
  • Frequency of Adverse Events [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
    Type and number of Adverse Events related to anti-IL-1 treatment (anakinra) during the initial 24 hour period of DKA treatment.

Estimated Enrollment: 21
Study Start Date: March 2012
Estimated Study Completion Date: December 2016
Primary Completion Date: March 2016 (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.

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.


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

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
  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 identifier: NCT01477476

Contact: Arleta Rewers, MD, Phd 303-725-2576

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   
Sponsors and Collaborators
University of Colorado, Denver
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Principal Investigator: Arleta Rewers, MD, Phd University of Colorado, Denver
  More Information

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
DKA TREATMENT PROTOCOL Barbara Davis Center for Childhood Diabetes, University of Colorado & The Children's Hospital Denver. . 2010.

Responsible Party: University of Colorado, Denver Identifier: NCT01477476     History of Changes
Other Study ID Numbers: 11-0814  P30DK057516 
Study First Received: November 18, 2011
Last Updated: April 20, 2016
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Diabetic Ketoacidosis
Acid-Base Imbalance
Autoimmune Diseases
Diabetes Complications
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases processed this record on April 27, 2016