Adrenal insufficiency Nutritional, Metabolic, Endocrine
Conditions
Interventions
Participants will attend 4 separate visits and will receive a different drug (either 500µg nasal tetracosactide (Nasacthin), nasal placebo, 250µg IV tetracosactide (Synacthen) (or 145µg/m2 for paediat
Sponsors
Sheffield Children's NHS Foundation Trust
Eligibility
Sex/Gender
All
Age
4 Years to 69 Years
Inclusion criteria
Inclusion criteria: Current participant inclusion criteria as of 17/11/2023: 1. Healthy men, women and children aged 4-69 years old 2. Able to comply with passive drool salivary sampling requirements 3. Provision of signed written informed consent Previous participant inclusion criteria: 1. Healthy men, women and children aged 2-69 years old 2. Able to comply with passive drool salivary sampling requirements 3. Provision of signed written informed consent
Exclusion criteria
Exclusion criteria: Current participant exclusion criteria as of 09/10/2024: 1. Known adrenal insufficiency, Cushing's syndrome or any other adrenal or pituitary gland disorder 2. Ongoing pregnancy 3. Use of oestrogen-containing hormonal contraception / Hormone Replacement Therapy (due to the effect on cortisol levels) 4. Known 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, including opioids, oral antifungals, loperamide 5. Currently prescribed anti-epileptic medication, such as sodium valproate, phenytoin, clonazepam, nitrazepam, phenobarbital or primidone 6. Known and active protein-losing disorders, e.g. enteropathy or nephrotic syndrome, who may have 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. Participants on regular, inhaled, topical, nasal, ocular, rectal, oral or intra-articular steroids for any indication in the last 3 months 9. Current uncontrolled active infection 10. BMI >35 kg/m² (or BMI >3 standard deviations (SD) above the mean for age and sex if <16 years) 11. Known or suspected alcohol dependence or drug misuse 12. Current smoker or vaper (or within 6 months of cessation) 13. Recent (within 1 week) liquorice ingestion (preparations containing glycyrrhizic acid only) 14. Individuals with a history of known salivary gland or oral mucosa pathology who are unable to produce a suitable salivary sample (e.g. as a consequence of drugs that cause dry mouth) 15. Previous severe allergic reaction or anaphylaxis or adverse reaction to any antigen of ACTH or Synacthen 16. Participation in another clinical trial of an investigational or licensed drug within the 3 months prior to inclusion in study, unless it is a clinical trial of the same IMP (i.e. Nasacthin), in which case only a 7-day washout period applies 17. Participants unable to comply with the requirements of the protocol 18. Participants with any other significant medical or psychiatric conditions that in the opinion of the investigator would preclude participation in the trial 19. For nasal visits only: coryzal symptoms within the last week (and will be asked to report any new symptoms occurring within 24 hours of the test) or heavy nosebleed within the previous 48 hours - just excluded from that visit Previous participant exclusion criteria: 1. Known adrenal insufficiency, Cushing's syndrome or any other adrenal or pituitary gland disorder 2. Ongoing pregnancy 3. Use of oestrogen-containing hormonal contraception / Hormone Replacement Therapy (due to the effect on cortisol levels) 4. Known 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, including opioids, oral antifungals, loperamide 5. Known and active protein-losing disorders, e.g. enteropathy or nephrotic syndrome, who may have a cortisol-binding globulin abnormality 6. Known clinical or biochemical evidence of hepatic or renal disease. Creatinine over twice the upper limit of normal (ULN) or elevated liver fu
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Comparison of mean serum cortisol concentration post-Nasacthin and Synacthen administration, measured using liquid chromatography with tandem mass spectrometry (LC-MS/MS) at baseline (pre-drug) and 30 minutes post-drug administration 2. Proportion of participants for which the Nasacthin test produces a rise above a pre-set threshold, out of those for whom the Synacthen test also produces a rise above a pre-set threshold, measured using LC-MS/MS at baseline and 30 minutes post-drug administration 3. Comparison of mean change from baseline in serum cortisol concentration post-active Nasacthin and nasal placebo administration, measured using LC-MS/MS at baseline and 30 minutes post-drug administration 4. Comparison of mean change from baseline in serum cortisol concentration post-active Synacthen and IV placebo administration, measured using LC-MS/MS at baseline and 30 minutes post-drug administration | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 09/10/2024: 1. Comparison of mean salivary cortisone concentration post-Nasacthin and Synacthen administration, measured using LC-MS/MS at baseline and 60 minutes post-drug administration. 2. Comparison of mean change from baseline in serum cortisol concentration post-Nasacthin and Synacthen administration, measured using LC-MS/MS at baseline and 30 minutes post-drug administration. 3. Comparison of mean serum cortisol concentration post-Nasacthin and Synacthen administration, measured using liquid chromatography with tandem mass spectrometry (LC-MS/MS) at baseline (pre-drug) and 60 minutes post-drug administration. 4. Comparison of mean change from baseline in serum cortisol concentration post-Nasacthin and Synacthen administration, measured using LC-MS/MS at baseline and 60 minutes post-drug administration. 5. Frequency of adverse events (AEs), serious adverse events (SAEs) and suspected unexpected serious adverse reactions (SUSARs) by the treatment arm, as reported by participants up to 48 hours after the study visit. 6. Analysis of participant and clinical workforce acceptability, usability and tolerability, measured using non-validated questionnaires, for participants at each study visit and for healthcare professionals at the end of the study; optional participant interviews after completion of study visits; and a stakeholder focus group at the end of the study. Previous secondary outcome measures: 1. Comparison of mean salivary cortisone concentration post-Nasacthin and Synacthen administration, measured using LC-MS/MS at baseline and 60 minutes post-drug administration. 2. Comparison of mean change from baseline in serum cortisol concentration post-Nasacthin and Synacthen administration, measured using LC-MS/MS at baseline and 30 minutes post-drug administration. 3. Frequency of adverse events (AEs), serious adverse events (SAEs) and suspected unexpected serious adverse reactions (SUSARs) by the treatment arm, as rep | — |
Countries
England, United Kingdom
Contacts
Public ContactKathryn Date
Outcome results
None listed