Adrenal insufficiency Nutritional, Metabolic, Endocrine
Conditions
Interventions
Participants will attend 2 separate visits and will receive a different drug (either 500µg nasal tetracosactide (Nasacthin) or 250µg IV tetracosactide (Synacthen) (or 145µg/m2 for paediatric participa
Sponsors
Sheffield Children's NHS Foundation Trust
Eligibility
Sex/Gender
All
Age
4 Years to 75 Years
Inclusion criteria
Inclusion criteria: Current key inclusion criteria as of 01/10/2025: 1. Known adrenal insufficiency 2. Confirmation of adrenal insufficiency with either: 2.1. A waking salivary cortisone <7 nmol/L at the time of diagnosis or since 2.2. A basal (non-stimulated) cortisol <150 nmol/L at the time of diagnosis or since 2.3. A peak on SST (stimulated cortisol) <250 nmol/L at the time of diagnosis or since 2.4. A non-stimulated cortisol 150-299 nmol/L or SST peak 250-299nmol/L, with a confirmed pathology compatible with a diagnosis of adrenal insufficiency AND a waking salivary cortisone <7 nmol/L 3. Able to comply with passive drool salivary sampling requirements 4. Able to provide signed written informed consent 5. Age 4-75 years Previous inclusion criteria as of 03/03/2025: 1. Known adrenal insufficiency 2. Confirmation of adrenal insufficiency with either a waking salivary cortisone of <7 nmol/L, basal cortisol <100 nmol/L or peak on SST <200 nmol/L at time of diagnosis or since 3. Able to comply with passive drool salivary sampling requirements 4. Able to provide signed written informed consent 5. Age 4-75 years Previous inclusion criteria: 1. Known adrenal insufficiency 2. Basal cortisol <100 nmol/L or peak on SST <200 nmol/L at time of diagnosis or since in last 6 months 3. Able to comply with passive drool salivary sampling requirements 4. Able to provide signed written informed consent 5. Age 4-75 years
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 03/03/2025: 1. Ongoing pregnancy 2. Use of oestrogen-containing hormonal contraception / Hormone Replacement Therapy (due to the effect on cortisol levels) 3. Co-morbid condition requiring daily administration of a medication that interferes with the metabolism of glucocorticoids, e.g. known to affect corticosteroid-binding globulin (CBG), including all oestrogens, or the hypothalamic-pituitary-adrenal (HPA) axis, such as loperamide, oral antifungals and opiates 4. Currently prescribed anti-epileptic medication, such as sodium valproate, phenytoin, clonazepam, nitrazepam, phenobarbital or primidone 5. Currently prescribed amphetamines, e.g. lisdexamfetamine, dexamphetamine 6. Known and active protein-losing disorder, e.g. enteropathy or nephrotic syndrome, which may result in a cortisol-binding globulin abnormality 7. Known clinical or biochemical evidence of hepatic or renal disease. Creatinine over twice the upper limit of normal (ULN) or elevated liver function tests (alanine transaminase (ALT) or aspartate transaminase (AST) >3 times the ULN 8. Current uncontrolled active infection (may include later in the trial at the clinician's discretion if completely resolved) 9. Known or suspected alcohol dependence or drug misuse 10. Current smoker or vaper (or within 6 months of cessation) 11. Recent (within the last 1 week) liquorice ingestion (preparations containing glycyrrhizic acid only) 12. History of known salivary gland or oral mucosa pathology, or unable to produce a suitable salivary sample (e.g. as a consequence of drugs that cause dry mouth) 13. Previous severe allergic reaction or anaphylaxis, or adverse reaction to any antigen of ACTH or Synacthen 14. Participation in another clinical trial of an investigational or licensed drug or device within the last 3 months 15. Unable to comply with the requirements of the protocol 16. Any other significant medical or psychiatric conditions that, in the opinion of the investigator, would preclude participation in the trial 17. For nasal visit only - active nasal symptoms, including Coryzal symptoms within the last week, active allergic rhinitis (hayfever) symptoms currently requiring medication, or heavy nosebleed within the previous 48 hours - just excluded from that visit Previous exclusion criteria: 1. Ongoing pregnancy 2. Use of oestrogen-containing hormonal contraception / Hormone Replacement Therapy (due to the effect on cortisol levels) 3. Co-morbid condition requiring daily administration of a medication that interferes with the metabolism of glucocorticoids, e.g. known to affect corticosteroid-binding globulin (CBG), including all oestrogens, or the hypothalamic-pituitary-adrenal (HPA) axis, such as loperamide, oral antifungals and opiates 4. Known and active protein losing disorder, e.g. enteropathy or nephrotic syndrome, which may result in a cortisol binding globulin abnormality 5. Known clinical or biochemical evidence of hepatic or renal disease. Creatinine over twice the upper limit of normal (ULN) or elevated liver function tests (alanine transaminase (ALT) or aspartate transaminase (AST) >3 times the ULN 6. Current uncontrolled active infection (may include later in the trial at clinician's discretion if completely resolved) 7. Known or suspected alcohol dependence or drug misuse 8. Current smoker or vaper (or within 6 months of cessation) 9. Recent (within last 1 week) liquorice ingestion (preparations containing glycyrrhizic acid on
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The proportion of participants with adrenal insufficiency (AI) diagnosed by the Nasacthin Test (Positive Percent Agreement) using serum cortisol at baseline and 30 minutes post-drug administration, measured using liquid chromatography with tandem mass spectrometry (LC-MS/MS). To be included in the analysis, participants will have been confirmed to have AI by assessment of serum cortisol at 30 minutes following the Synacthen test. | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 03/03/2025: 1. The proportion of participants with adrenal insufficiency (AI) diagnosed by the Nasacthin Test (Positive Percent Agreement) using serum cortisol at baseline and 60 minutes post-drug administration, measured using liquid chromatography with tandem mass spectrometry (LC-MS/MS). To be included in the analysis, participants will have been confirmed to have AI by assessment of serum cortisol at 30 minutes following the Synacthen test. 2. Frequency of adverse events (AEs), serious adverse events (SAEs) and suspected unexpected serious adverse reactions (SUSARs) by treatment arm, as reported by participants up to 48 hours after each study visit. Any SAEs/SUSARs will be followed to the point of resolution. 3. Analysis of participant and healthcare professional acceptability, usability and tolerability of the Nasacthin test, measured using non-validated questionnaires completed by participants at the end of each study visit and by healthcare professionals at the end of the study; and optional participant and stakeholder focus groups held at the end of the study. Previous secondary outcome measures: 1. Frequency of adverse events (AEs), serious adverse events (SAEs) and suspected unexpected serious adverse reactions (SUSARs) by treatment arm, as reported by participants up to 48 hours after each study visit. Any SAEs/SUSARs will be followed to the point of resolution. 2. Analysis of participant and healthcare professional acceptability, usability and tolerability of the Nasacthin test, measured using non-validated questionnaires completed by participants at the end of each study visit and by healthcare professionals at the end of the study; and optional participant and stakeholder focus groups held at the end of the study. | — |
Countries
England, United Kingdom
Contacts
Public ContactKathryn Date
Outcome results
None listed