Clinical trial NCT03366298: Pharmacokinetics of Intramuscular Adrenaline in Food--Allergic Teenagers
Official title: Pharmacokinetics of Intramuscular Adrenaline in Food--Allergic Teenagers: Does Dose Matter?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Anaphylaxis
Lead sponsor: Imperial College London
Sponsor class: OTHER
First posted: 2017-12-08
Enrollment: 12
Sex: ALL
Minimum age (years): 13
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Plasma Catecholamine Levels (Maximum Concentration, Cmax)
timeFrame: 3 hours
measure: Plasma Catecholamine Levels (Time to Maximum Concentration, Tmax)
timeFrame: 3 hours
measure: Plasma Catecholamine Levels (Maximum Concentration, Area-under-curve (AUC))
timeFrame: At at the following timepoints following injection: 5, 10, 15, 20, 30, 45, 60, 80, 100, 120 and 180 minutes
Secondary outcomes:
measure: Change in Heart Rate Following Self-injection of Adrenaline (300mcg, 500mcg) on Separate Occasions.
timeFrame: 3 hours
measure: Change in Blood Pressure Following Self-injection of Adrenaline (300mcg, 500mcg) on Separate Occasions.
timeFrame: 3 hours
measure: Change in Stroke Volume Following Self-injection of Adrenaline (300mcg, 500mcg) on Separate Occasions.
timeFrame: 3 hours
measure: Impact of Needle Length on Pharmacokinetics (Plasma Catecholamine Levels: Cmax)
timeFrame: 3 hours
measure: Impact of Needle Length on Pharmacokinetics (Plasma Catecholamine Levels: Tmax)
timeFrame: 3 hours
measure: Impact of Needle Length on Pharmacokinetics (Plasma Catecholamine Levels: AUC)
timeFrame: 3 hours
measure: Impact of Needle Length on Pharmacodynamics (Cardiovascular Parameters: Heart Rate)
timeFrame: 3 hours
measure: Impact of Needle Length on Pharmacodynamics (Cardiovascular Parameters: Blood Pressure)
timeFrame: 3 hours
measure: Impact of Needle Length on Pharmacodynamics (Cardiovascular Parameters: Stroke Volume)
timeFrame: 3 hours
measure: Adverse Events Following Self-administration of Adrenaline Via Autoinjector Device
timeFrame: 1 day
measure: Change in Health-related Quality of Life (HRQL) as Measured Using FAQLQ
timeFrame: 1 month
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Imperial College London / Imperial College Healthcare NHS Trust
Study officials:
affiliation: Imperial College London
name: Paul J Turner, FRACP PhD
role: PRINCIPAL_INVESTIGATOR
References: