NeSST2: The Development of a Noninvasive Short Synacthen Test

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.

Inclusion criteria

Stage 1b+c:

• Healthy, male volunteers aged between 18-64 with none of the exclusion criteria listed below.

Stage 2:

• Healthy children of either sex, aged between 2 and 15 years (up to their 16th birthday) with none of the exclusion criteria listed below.

Stage 3:

• Healthy children of both sexes, aged between 0-18 years without exclusion criteria 1,2,3,5,6,7,8,9,10,11,12,14 listed below.

Stage 4:

• Asthmatic children of both sexes, aged between 6 months and 15 years, prescribed regular inhaled corticosteroids and without exclusion criteria 1,5,9,10,11,12, and 14 listed below.

Exclusion criteria

• Past or present history of an endocrinopathy (all stages)
• Past or present history of asthma (stages 1b+c,2,3)
• Past or present history of allergic rhinitis (stages 1b+c,2,3)
• Past or present history of peptic ulcer disease/GI bleed/significant dyspepsia (stages 1b+c,2)
• Past history of intra-cranial or renal/adrenal pathology (all stages)
• Presently on any medication (stages 1b+c,2,3)
• Presently, or within the last 3 months, been prescribed any type of corticosteroid (oral, inhaled, nasal, rectal, intravenous, intramuscular, intra-articular, intra-ocular, topical) (stages 1b+c,2,3)
• Ever been prescribed a prolonged course of oral corticosteroids (more than 1 month) (stages 1b+c,2,3)
• Previous adverse reaction (including mild hypersensitivity) to ACTH or Synacthen (all stages)
• Previous severe allergic reaction or anaphylaxis (all stages)
• Coryzal symptoms within the last week (and will be asked to report any new symptoms occurring within 24 hours of the test) (all stages)
• Current smoker (all stages)
• Body Mass Index less than 18.5 or more than 30kg/m2 (stages 1b+c) outside 3rd to 97th centiles for ages and sex (stage 2)
• Currently pregnant (stages 2,3,4)
• Currently anaemic (stages 1b+c,2)