CClinicalTrials.gg
RecruitingNCT03514589NeSST2Updated Dec 3, 2024

NeSST2: The Development of a Noninvasive Short Synacthen Test

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

From the registry’s dates

  • Primary completion was expected by Dec 2025, 10 months ago, but the record still lists the study as recruiting.
  • Registered 3 years 2 months after the study started (first participant enrolled Oct 2012, registered Dec 2015).
  • Started Oct 2012; still recruiting 13 years 11 months later.
Phase
Phase 2
Study type
Interventional
Enrollment
12
Allocation
Randomized
Ages
6 Months to 60 Years
Sex
Male
01

Study summary

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.

Read the detailed description

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.

02

Conditions studied

  • Adrenal Suppression
03

In context

Lead sponsor

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.

04

Who can participate

Ages eligible
6 Months to 60 Years
Sexes eligible
Male
Accepts healthy volunteers
Yes

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

Exclusion Criteria:

  1. Past or present history of an endocrinopathy (all stages)
  2. Past or present history of asthma (stages 1b+c,2,3)
  3. Past or present history of allergic rhinitis (stages 1b+c,2,3)
  4. Past or present history of peptic ulcer disease/GI bleed/significant dyspepsia (stages 1b+c,2)
  5. Past history of intra-cranial or renal/adrenal pathology (all stages)
  6. Presently on any medication (stages 1b+c,2,3)
  7. 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)
  8. Ever been prescribed a prolonged course of oral corticosteroids (more than 1 month) (stages 1b+c,2,3)
  9. Previous adverse reaction (including mild hypersensitivity) to ACTH or Synacthen (all stages)
  10. Previous severe allergic reaction or anaphylaxis (all stages)
  11. Coryzal symptoms within the last week (and will be asked to report any new symptoms occurring within 24 hours of the test) (all stages)
  12. Current smoker (all stages)
  13. 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)
  14. Currently pregnant (stages 2,3,4)
  15. Currently anaemic (stages 1b+c,2)
05

Study design

Phase
Phase 2
Primary purpose
Diagnostic
Allocation
Randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
12 participants (estimated)

Study arms

  • Active comparator
    Arm 1

    250 mcg IV synacthen

    Drug: nasal Tetracosactide

  • Experimental
    Arm 2

    Nasal Synacthen

    Drug: IV tetracosactide

Interventions

  • Drugnasal Tetracosactide

    Bioavailability of nasal synacthen compared to IV comparator

    Also known as: cosyntropin, Synacthen

  • DrugIV tetracosactide

    Bioavailability of nasal synacthen compared to IV comparator

    Also known as: cosyntropin, synacthen

06

What researchers measure

Primary outcomes

  1. Peak plasma cortisol concentration (Cmax)

    Peak plasma cortisol following synacthen

    Time frame: 6 months

  2. Time of peak plasma cortisol concentration (Tmax)

    Time of Cmax

    Time frame: 6 months

  3. 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

  4. Area under the curve for plasma Synacthen (nasal compared to IV)

    Total exposure to synacthen

    Time frame: 6 months

  5. Area under the curve for plasma cortisol (nasal compared to IV)

    Total exposure to plasma cortisol following synacthen

    Time frame: 6 months

Secondary outcomes

  1. 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)

  2. Correlation of plasma cortisol with salivary cortisol

    relationship of peak plasma cortisol and peak salivary cortisol

    Time frame: 6 months

07

Study locations

1 of 1 sites recruiting
08

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Dec 3, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT03514589
Lead sponsor
Sheffield Children's NHS Foundation Trust
Responsible party
Sponsor
First posted
May 2, 2018
Start date
Oct 12, 2012
Primary completion
Dec 1, 2025 (estimated)
Completion
Dec 1, 2025 (estimated)
Last update
Dec 3, 2024

Study contacts

Meena Balasubramanian
Contact
meena.balasubramanian@nhs.net
Gillian Gatenby
Contact
gillian.gatenby@nhs.net
Charlotte Elder
principal investigator · Investigator

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Interested in this study?

Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.

Contact study team

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion