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Type I DiabetesPhase 2NCT01477476

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

A Phase 2 study testing Anakinra in people with Type I Diabetes, run by University of Colorado, Denver at 2 sites in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 8 to 18 years
Conditions the study is for
Type I Diabetes
What is being tested?
Anakinra
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
2 sitesUnited States
Study dates
Mar 2012to 22 Apr 2016
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 8 to 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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
Show all 11Show fewer
  • Hematology:
  • WBC >3000 x 109/L;
  • platelets >100,000 x 109/L;
  • hemoglobin >10.0 g/dL
  • Negative blood pregnancy test in females.

Who cannot join

  • 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
Show all 16Show fewer
  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites
  • Childrens Hospital Colorado

    Aurora, Colorado, 80045

  • University of Colorado, Anschutz Medical Campus

    Aurora, Colorado, 80045

Other trials in United States

About this study

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

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.

Read the 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.

Conditions
Type I Diabetes
Being tested
Anakinra, Placebo Comparator
Keywords
DKA, Diabetes, Type I Diabetes
Medical subject headings
Diabetes Mellitus, Type 1, Diabetes Mellitus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AnakinraDrug

    Also called anti Interleukin 1 receptor antibodies

    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.

  • Placebo ComparatorOther

    A placebo will be given to 7 subjects.

Study groups in NCT01477476
Study groupRoleWhat they receive
Active TreatmentActive comparator14 subjects with receive active treatment with Anakinra.
Receives: Drug: Anakinra
PlaceboPlacebo comparator7 subjects will receive the placebo comparator.
Receives: Other: Placebo Comparator

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Frequency of Adverse Events

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

    Measured: 24 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Nov 2011 (estimated)
  2. Study startMar 2012
  3. Primary completionMar 2016
  4. Study completion22 Apr 2016

Why it stopped: funding loss, no data was ever collected

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01477476
Sponsor's protocol ID
11-0814
Other IDs
P30DK057516
Status last verified
Apr 2019
First submitted
18 Nov 2011
Last updated
18 Apr 2019
Results posted
No
Data monitoring committee
Yes

Publications

  • Rewers A, Chase HP, Mackenzie T, Walravens P, Roback M, Rewers M, Hamman RF, Klingensmith G. Predictors of acute complications in children with type 1 diabetes. JAMA. 2002 May 15;287(19):2511-8. doi: 10.1001/jama.287.19.2511.

    PubMed 12020331
  • Rewers A, Klingensmith G, Davis C, Petitti DB, Pihoker C, Rodriguez B, Schwartz ID, Imperatore G, Williams D, Dolan LM, Dabelea D. Presence of diabetic ketoacidosis at diagnosis of diabetes mellitus in youth: the Search for Diabetes in Youth Study. Pediatrics. 2008 May;121(5):e1258-66. doi: 10.1542/peds.2007-1105.

    PubMed 18450868
  • Maniatis AK, Goehrig SH, Gao D, Rewers A, Walravens P, Klingensmith GJ. Increased incidence and severity of diabetic ketoacidosis among uninsured children with newly diagnosed type 1 diabetes mellitus. Pediatr Diabetes. 2005 Jun;6(2):79-83. doi: 10.1111/j.1399-543X.2005.00096.x.

    PubMed 15963034
  • Muir AB, Quisling RG, Yang MC, Rosenbloom AL. Cerebral edema in childhood diabetic ketoacidosis: natural history, radiographic findings, and early identification. Diabetes Care. 2004 Jul;27(7):1541-6. doi: 10.2337/diacare.27.7.1541.

    PubMed 15220225
  • Glaser NS, Wootton-Gorges SL, Buonocore MH, Marcin JP, Rewers A, Strain J, DiCarlo J, Neely EK, Barnes P, Kuppermann N. Frequency of sub-clinical cerebral edema in children with diabetic ketoacidosis. Pediatr Diabetes. 2006 Apr;7(2):75-80. doi: 10.1111/j.1399-543X.2006.00156.x.

    PubMed 16629712
  • Edge JA, Hawkins MM, Winter DL, Dunger DB. The risk and outcome of cerebral oedema developing during diabetic ketoacidosis. Arch Dis Child. 2001 Jul;85(1):16-22. doi: 10.1136/adc.85.1.16.

    PubMed 11420189
  • Edge JA. Cerebral oedema during treatment of diabetic ketoacidosis: are we any nearer finding a cause? Diabetes Metab Res Rev. 2000 Sep-Oct;16(5):316-24. doi: 10.1002/1520-7560(2000)9999:99993.0.co;2-r.

    PubMed 11025556
  • Glaser N, Barnett P, McCaslin I, Nelson D, Trainor J, Louie J, Kaufman F, Quayle K, Roback M, Malley R, Kuppermann N; Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics. Risk factors for cerebral edema in children with diabetic ketoacidosis. The Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics. N Engl J Med. 2001 Jan 25;344(4):264-9. doi: 10.1056/NEJM200101253440404.

    PubMed 11172153
  • Wolfsdorf J, Glaser N, Sperling MA; American Diabetes Association. Diabetic ketoacidosis in infants, children, and adolescents: A consensus statement from the American Diabetes Association. Diabetes Care. 2006 May;29(5):1150-9. doi: 10.2337/diacare.2951150. No abstract available.

    PubMed 16644656
  • Blamire AM, Anthony DC, Rajagopalan B, Sibson NR, Perry VH, Styles P. Interleukin-1beta -induced changes in blood-brain barrier permeability, apparent diffusion coefficient, and cerebral blood volume in the rat brain: a magnetic resonance study. J Neurosci. 2000 Nov 1;20(21):8153-9. doi: 10.1523/JNEUROSCI.20-21-08153.2000.

    PubMed 11050138
  • Hoffman WH, Burek CL, Waller JL, Fisher LE, Khichi M, Mellick LB. Cytokine response to diabetic ketoacidosis and its treatment. Clin Immunol. 2003 Sep;108(3):175-81. doi: 10.1016/s1521-6616(03)00144-x.

    PubMed 14499240
  • Glaser N. Cerebral injury and cerebral edema in children with diabetic ketoacidosis: could cerebral ischemia and reperfusion injury be involved? Pediatr Diabetes. 2009 Dec;10(8):534-41. doi: 10.1111/j.1399-5448.2009.00511.x. Epub 2009 Oct 10. No abstract available.

    PubMed 19821944
  • Mulcahy NJ, Ross J, Rothwell NJ, Loddick SA. Delayed administration of interleukin-1 receptor antagonist protects against transient cerebral ischaemia in the rat. Br J Pharmacol. 2003 Oct;140(3):471-6. doi: 10.1038/sj.bjp.0705462. Epub 2003 Aug 26.

    PubMed 12970087
  • Banwell V, Sena ES, Macleod MR. Systematic review and stratified meta-analysis of the efficacy of interleukin-1 receptor antagonist in animal models of stroke. J Stroke Cerebrovasc Dis. 2009 Jul-Aug;18(4):269-76. doi: 10.1016/j.jstrokecerebrovasdis.2008.11.009.

    PubMed 19560680
  • Clark SR, McMahon CJ, Gueorguieva I, Rowland M, Scarth S, Georgiou R, Tyrrell PJ, Hopkins SJ, Rothwell NJ. Interleukin-1 receptor antagonist penetrates human brain at experimentally therapeutic concentrations. J Cereb Blood Flow Metab. 2008 Feb;28(2):387-94. doi: 10.1038/sj.jcbfm.9600537. Epub 2007 Aug 8.

    PubMed 17684519

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Anakinra in people with Type I Diabetes, run by University of Colorado, Denver at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 18 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Frequency of Adverse Events (time frame: 24 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01477476, which also lists 42 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2019.

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