Adrenal SuppressionPhase 2NeSST2NCT03514589
NeSST2: The Development of a Noninvasive Short Synacthen Test
A Phase 2 study testing nasal Tetracosactide and IV tetracosactide in people with Adrenal Suppression, run by Sheffield Children's NHS Foundation Trust at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 months to 60 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Adrenal Suppression
- What is being tested?
- nasal Tetracosactide and IV tetracosactide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 12 Oct 2012to 1 Dec 2025
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 60 years
- Men only
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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)
Show all 15Show fewer
- 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)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Meena Balasubramanian contact
Gillian Gatenby contact
United Kingdom1 site, 1 recruiting
- Recruiting
Sheffield Children's NHS Foundation Trust
Sheffield, Sheffield (South Yorkshire District), S10 2TH
Meena Balasubramanian, meena.balasubramanian@nhs.net
Gillian Gatenby, gillian.gatenby@nhs.net
About this study
Official title: NeSST2: A Multi-stage Clinical Study to Develop a Non-invasive Short Synacthen Test (SST)
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.
- Conditions
- Adrenal Suppression
- Being tested
- nasal Tetracosactide, IV tetracosactide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
nasal TetracosactideDrug
Also called cosyntropin, Synacthen
Bioavailability of nasal synacthen compared to IV comparator
IV tetracosactideDrug
Also called cosyntropin, synacthen
Bioavailability of nasal synacthen compared to IV comparator
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Active comparator | 250 mcg IV synacthen Receives: Drug: nasal Tetracosactide |
| Arm 2 | Experimental | Nasal Synacthen Receives: Drug: IV tetracosactide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak plasma cortisol concentration (Cmax)
Peak plasma cortisol following synacthen
Measured: 6 months
Time of peak plasma cortisol concentration (Tmax)
Time of Cmax
Measured: 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.
Measured: 6 months
Area under the curve for plasma Synacthen (nasal compared to IV)
Total exposure to synacthen
Measured: 6 months
Area under the curve for plasma cortisol (nasal compared to IV)
Total exposure to plasma cortisol following synacthen
Measured: 6 months
Secondary outcomes (2)
Tolerability and acceptability of nasal Synacthen test
Questionnaire answers to questions on tolerability and acceptability of nasal Synacthen test. Safety data
Measured: Course of the study (2.5 years)
Correlation of plasma cortisol with salivary cortisol
relationship of peak plasma cortisol and peak salivary cortisol
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2018
- Study start12 Oct 2012
- Primary completion1 Dec 2025 (estimated)
- Study completion1 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Adrenal SuppressionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Single group
- Model description
- Current stage is stage 3 (Sept 2023), an open label study of nasal Synacthen in healthy children aged 0-18 to derived normative reference data. Previous stages: 1a: 12 healthy adult males, 4 arms (dose selection studying nasal synacthen 100 mcg + chitosan, 500 mcg and 500 mcg + chitosan against 1mcg IV Synacthen) 1b: 6 healthy adult males 1 arm (repeatability: two further 500 mcg + chitosan visits) 1c: 12 healthy adult males 3 arms (dose rangign study: 500 mcg + chitosan, 1mg + chitosan against 250 mcg IV Synacthen comparator) 2: Healthy children aged 2-15 (500 mcg + chitosan, against 145 mcg/m2 IV Synacthen comparator)
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sheffield Children's NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Charlotte Elder, Principal investigator, Investigator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03514589
- Sponsor's protocol ID
- SCH/12/043
- Acronym
- NeSST2
- Status last verified
- Dec 2024
- First submitted
- 21 Dec 2015
- Last updated
- 3 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NeSST2: A Multi-stage Clinical Study to Develop a Non-invasive Short Synacthen Test (SST)
- ClinicalTrials.gov ID
- NCT03514589
- Acronym / sponsor ID
- NeSST2 / SCH/12/043
- Conditions
- Adrenal Suppression
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Sheffield Children's NHS Foundation TrustUniversity, hospital or other
- Study start
- 12 Oct 2012 (actual)
- Primary completion
- 1 Dec 2025 (estimated)
- Study completion
- 1 Dec 2025 (estimated)
- First posted
- 2 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Current stage is stage 3 (Sept 2023), an open label study of nasal Synacthen in healthy children aged 0-18 to derived normative reference data. Previous stages: 1a: 12 healthy adult males, 4 arms (dose selection studying nasal synacthen 100 mcg + chitosan, 500 mcg and 500 mcg + chitosan against 1mcg IV Synacthen) 1b: 6 healthy adult males 1 arm (repeatability: two further 500 mcg + chitosan visits) 1c: 12 healthy adult males 3 arms (dose rangign study: 500 mcg + chitosan, 1mg + chitosan against 250 mcg IV Synacthen comparator) 2: Healthy children aged 2-15 (500 mcg + chitosan, against 145 mcg/m2 IV Synacthen comparator)
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Active comparator | Drug: nasal Tetracosactide250 mcg IV synacthen |
| Arm 2 | Experimental | Drug: IV tetracosactideNasal Synacthen |
Who may qualify
- Ages
- 6 months to 60 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- Healthy, male volunteers aged between 18-64 with none of the exclusion criteria listed below.
- Healthy children of either sex, aged between 2 and 15 years (up to their 16th birthday) with none of the exclusion criteria listed below.
- 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.
- 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.
Key exclusion criteria (15 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| nasal TetracosactideAlso: cosyntropin, SynacthenBioavailability of nasal synacthen compared to IV comparator | Drug | Arm 1 |
| IV tetracosactideAlso: cosyntropin, synacthenBioavailability of nasal synacthen compared to IV comparator | Drug | Arm 2 |
Primary outcome
Peak plasma cortisol concentration (Cmax)
Time frame: 6 months
Peak plasma cortisol following synacthen
Time of peak plasma cortisol concentration (Tmax)
Time frame: 6 months
Time of Cmax
Bioavailability of nasal Synacthen (compared to IV Synacthen)
Time frame: 6 months
Proportion of synacthen measurable in blood following administration (IV or nasal) and so is able to have an active effect.
Area under the curve for plasma Synacthen (nasal compared to IV)
Time frame: 6 months
Total exposure to synacthen
Area under the curve for plasma cortisol (nasal compared to IV)
Time frame: 6 months
Total exposure to plasma cortisol following synacthen
2 secondary outcomes
Tolerability and acceptability of nasal Synacthen test
Time frame: Course of the study (2.5 years)
Correlation of plasma cortisol with salivary cortisol
Time frame: 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Meena Balasubramanian contact
Gillian Gatenby contact
Charlotte Elder principal investigator
Investigator
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing nasal Tetracosactide and IV tetracosactide in people with Adrenal Suppression, run by Sheffield Children's NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 3 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Meena Balasubramanian (meena.balasubramanian@nhs.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Peak plasma cortisol concentration (Cmax) (time frame: 6 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Dec 2024.