Pharmacokinetics of Intramuscular Adrenaline in Food--Allergic Teenagers
Condition: Anaphylaxis
MeSH terms: Anaphylaxis
Intervention: Epipen 0.3mg; Emerade 300mcg; Emerade 500mcg
Intervention description: Epipen 0.3mg auto-injector; Emerade 300mcg auto-injector; Emerade 500mcg auto-injector
Intervention MeSH terms: Epinephrine; Racepinephrine; Epinephryl borate
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 13 Years
Maximum age: 18 Years
Healthy volunteers: No

Summary:

      Food allergy affects up to 2% of adults and 8% of children in the United Kingdom (UK), and is
      a major public health issue. It is the commonest cause of life-threatening allergic reactions
      (anaphylaxis), which can be fatal. Adrenaline (epinephrine) auto-injector (AAI) devices are
      the first-line treatment for anaphylaxis, yet in a UK survey, over 80% of 245 teenagers
      experiencing anaphylaxis did not use their AAI. Delays in, or lack of adrenaline
      (epinephrine) administration during anaphylaxis are risk factors for fatal anaphylaxis.

      In 2010, a coroner's investigation into the death of a food-allergic teenager in the UK
      raised several questions around AAI safety and efficacy, since the teenager died despite
      administering her auto-injector device. This prompted a review by the Medicines and
      Healthcare products Regulatory Agency (MHRA) in 2014 into the clinical and quality
      considerations of AAIs. Two recommendations which came from the review was that companies
      'should be encouraged to develop a 0.5mg [dose] AAI.' In the UK currently only Emerade, one
      of the three companies selling AAIs, manufactures a 0.5mg (500mcg) version. Emerade also has
      a longer needle length (23mm) compared to other AAIs (typically 15mm).

      The investigators plan to formally assess the pharmacokinetics (PK) and pharmacodynamics (PD)
      of self-injection with intramuscular adrenaline (epinephrine) in teenagers at risk of
      anaphylaxis due to food allergy, and have been prescribed AAI.

        1. The investigators will compare self-injection with 300mcg vs 500mcg in teenagers of body
           weight >40kg. In a 40kg person, an adrenaline dose of 300mcg results in an effective
           UNDER-dosing of 30% by body weight.

        2. The investigators will also assess the impact of needle length on injection, by
           comparing two different devices, both of which deliver 300mcg, but one via a 15mm needle
           and the other with a 23mm needle.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age 13 - 18 years inclusive

          -  Body mass >40kg

          -  Prescription of AAI due to physician diagnosis of Immunoglobulin E-mediated food
             allergy.

          -  Written informed consent from parent/guardian together with patient assent, for
             participants under 16 years of age. For young people age 16+ years, consent will be
             obtained from the participant themselves.

        Exclusion Criteria:

          -  Known cardiac comorbidity (including hypertension, structural or electrophysiological
             diagnoses) or prescribed a medicine to control cardiovascular disease/hypertension.

          -  Known endocrine or renal disease

          -  Poorly controlled asthma requiring daily rescue treatment with a bronchodilator.

          -  Pregnancy

          -  Unwilling or unable to comply with study requirements