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

This study has been terminated.
(funding loss and only one subject enrolled)
Sponsor:
ClinicalTrials.gov Identifier:
NCT01477476
First Posted: November 22, 2011
Last Update Posted: July 2, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
University of Colorado, Denver
  Purpose
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
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.

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 ]
    Type and number of Adverse Events related to anti-IL-1 treatment (anakinra) during the initial 24 hour period of DKA treatment.


Enrollment: 1
Study Start Date: March 2012
Study Completion Date: April 22, 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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   8 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01477476


Locations
United States, Colorado
Childrens Hospital Colorado
Aurora, Colorado, United States, 80045
University of Colorado, Anschutz Medical Campus
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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
DKA TREATMENT PROTOCOL Barbara Davis Center for Childhood Diabetes, University of Colorado & The Children's Hospital Denver. http://www.ucdenver.edu/academics/colleges/medicalschool/centers/BarbaraDavis/Pages/contact.aspx . 2010.

Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT01477476     History of Changes
Other Study ID Numbers: 11-0814
P30DK057516 ( U.S. NIH Grant/Contract )
First Submitted: November 18, 2011
First Posted: November 22, 2011
Last Update Posted: July 2, 2017
Last Verified: June 2017

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

Additional relevant MeSH terms:
Diabetes Mellitus
Acidosis
Diabetes Mellitus, Type 1
Diabetic Ketoacidosis
Ketosis
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Acid-Base Imbalance
Autoimmune Diseases
Immune System Diseases
Diabetes Complications
Interleukin 1 Receptor Antagonist Protein
Antirheumatic Agents