NeSST2: The Development of a Noninvasive Short Synacthen Test

NCT03514589 | Recruiting Phase 2 DMC

• 1 other identifier: SCH/12/043
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Adrenal Suppression

Outcome Measures

Primary Outcomes (5)

• Peak plasma cortisol concentration (Cmax)

  Peak plasma cortisol following synacthen

  6 months

• Time of peak plasma cortisol concentration (Tmax)

  Time of Cmax

  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.

  6 months

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

  Total exposure to synacthen

  6 months

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

  Total exposure to plasma cortisol following synacthen

  6 months

Secondary Outcomes (2)

• Tolerability and acceptability of nasal Synacthen test

  Course of the study (2.5 years)

• Correlation of plasma cortisol with salivary cortisol

  6 months

Study Arms (2)

Arm 1

ACTIVE COMPARATOR

250 mcg IV synacthen

Drug: nasal Tetracosactide

Arm 2

EXPERIMENTAL

Nasal Synacthen

Drug: IV tetracosactide

Interventions

nasal Tetracosactide DRUG

Bioavailability of nasal synacthen compared to IV comparator

Also known as: cosyntropin, Synacthen

Arm 1

IV tetracosactide DRUG

Bioavailability of nasal synacthen compared to IV comparator

Also known as: cosyntropin, synacthen

Arm 2

Eligibility Criteria

• Age: 6 Months - 60 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Stage 1b+c:

You may not qualify if:

• Stage 2:
• Stage 3:
• Stage 4:
• 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)

Sponsors & Collaborators

• Sheffield Children's NHS Foundation Trust: lead

Study Sites (1)

Sheffield Children's NHS Foundation Trust

Sheffield, Sheffield (South Yorkshire District), S10 2TH, United Kingdom

RECRUITING

MeSH Terms

Interventions

Cosyntropin; adrenocorticotropin zinc

Intervention Hierarchy (Ancestors)

Adrenocorticotropic Hormone; Melanocortins; Pro-Opiomelanocortin; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormones, Anterior; Pituitary Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins

Study Officials

• Charlotte Elder

  Investigator

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Meena Balasubramanian

CONTACT

meena.balasubramanian@nhs.net

Gillian Gatenby

CONTACT

gillian.gatenby@nhs.net

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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)

Study Record Dates

• First Submitted: December 21, 2015
• First Posted: May 2, 2018
• Study Start: October 12, 2012
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: December 3, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)