A Phase 2 interventional study of nasal Tetracosactide and IV tetracosactide in Adrenal Suppression, sponsored by Sheffield Children's NHS Foundation Trust. Recruiting at 1 site in United Kingdom. Open to male participants aged 6 Months to 60 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-12-03.
Sponsored by Sheffield Children's NHS Foundation Trust · Phase 2, Interventional, and Diagnostic
Recently there has been concern about the effect of inhaled steroids, routinely used in the treatment of asthma, on the body's ability to produce its natural stress hormone cortisol. Failure of adequate cortisol production in times of stress e.g. illness, can result in serious illness or death. Patients receiving longterm steroid treatment may have reduced levels of cortisol and not be able to produce adequate amounts in times of need, a process called adrenal suppression. Initially it was thought that the absorption of inhaled steroids into the bloodstream would be too low to cause adrenal suppression however high profile deaths followed by a national survey revealed a number of fatal or near fatal cases of adrenal suppression. The vast majority of these were in children. Since then doctors have been encouraged to ensure that children on high doses of inhaled steroids carry a steroid alert card and that the ability of their adrenal glands to produce adequate amounts of cortisol is checked. However it is unknown what dose of inhaled steroids puts one at risk, whether age or gender affects one's risk and when to check the function of the adrenal gland.
The Short Synacthen Test (SST) investigates the ability of the body's adrenal glands to produce cortisol. Presently the SST requires intravenous (i.v) cannulation through which Synacthen is injected to stimulate the adrenal glands and multiple blood samples are collected to assess the response in terms of cortisol production. It is invasive, time consuming and unpleasant for the child. Our project aims to produce a noninvasive alternative to the current SST, with Synacthen given nasally and using saliva to measure the subsequent production of cortisol. A noninvasive test will allow us to establish the first normal ranges for children and determine which children with asthma are at risk of adrenal suppression.
The success of the nasal administration of a novel formulation of Synacthen to adults was the first step in a work-stream, which aims to develop the clinical applicability of the non-invasive SST in addition to using it as an important research tool. The invasive nature of the current diagnostic test makes large cohort research impracticable. Having gained proof of concept with the initial study we will now go on to gained detailed pharmacokinetic information in adults with the IV comparator of the 250 mcg test in addition to the data already gained for the 1 mcg test. We will test two doses of nasal Synacthen. We will do intra-individual variation work also.
The next stage will then to be to perform pharmacokinetic validation of the nasal Synacthen plus chitosan dose in twenty children in order to establish that the chosen dose, peak cortisol response, bioavailability and pharmacokinetics are similar in the paediatric population. This will require 40 visits to our Childrens' Clinical Research Facility.
In order to obtain the quality of pharmacokinetic data required for commercial regulatory approvals an improved Synacthen assay is required. This work is ongoing in collaboration with ACTH assay experts at the University of Manchester.
Sheffield Children's NHS Foundation Trust is the lead sponsor of 51 studies on the registry; 9 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Stage 1b+c:
Stage 2:
Stage 3:
Stage 4:
Exclusion Criteria:
250 mcg IV synacthen
Drug: nasal Tetracosactide
Nasal Synacthen
Drug: IV tetracosactide
Bioavailability of nasal synacthen compared to IV comparator
Also known as: cosyntropin, Synacthen
Bioavailability of nasal synacthen compared to IV comparator
Also known as: cosyntropin, synacthen
Peak plasma cortisol concentration (Cmax)
Peak plasma cortisol following synacthen
Time frame: 6 months
Time of peak plasma cortisol concentration (Tmax)
Time of Cmax
Time frame: 6 months
Bioavailability of nasal Synacthen (compared to IV Synacthen)
Proportion of synacthen measurable in blood following administration (IV or nasal) and so is able to have an active effect.
Time frame: 6 months
Area under the curve for plasma Synacthen (nasal compared to IV)
Total exposure to synacthen
Time frame: 6 months
Area under the curve for plasma cortisol (nasal compared to IV)
Total exposure to plasma cortisol following synacthen
Time frame: 6 months
Tolerability and acceptability of nasal Synacthen test
Questionnaire answers to questions on tolerability and acceptability of nasal Synacthen test. Safety data
Time frame: Course of the study (2.5 years)
Correlation of plasma cortisol with salivary cortisol
relationship of peak plasma cortisol and peak salivary cortisol
Time frame: 6 months
Plan to share: No
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Sheffield Children's NHS Foundation Trust