A healthy volunteer study to determine the effectiveness of a needle-free test for the diagnosis of adrenal insufficiency

Not Applicable

• Conditions: Adrenal insufficiency; Nutritional, Metabolic, Endocrine

• Registration Number: ISRCTN62724177
• Lead Sponsor: Sheffield Children's NHS Foundation Trust

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-09-28
• Last Update Posted: 22 July 2024
• Study Completion: 2025-02-28

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 32

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

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 function tests (alanine transaminase (ALT) or aspartate transaminase (AST) >3 times the ULN).
7. Participants on regular, inhaled, topical, nasal, ocular, rectal, oral or intra-articular steroids for any indication in the last 3 months
8. Current uncontrolled active infection
9. BMI >35 kg/m² (or BMI >3 standard deviations (SD) above the mean for age and sex if <16 years)
10. Known or suspected alcohol dependence or drug misuse
11. Current smoker or vaper (or within 6 months of cessation)
12. Recent (within 1 week) liquorice ingestion (preparations containing glycyrrhizic acid only)
13. 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)
14. Previous severe allergic reaction or anaphylaxis or adverse reaction to any antigen of ACTH or Synacthen
15. Participation in another clinical trial of an investigational or licensed drug within the 3 months prior to inclusion in study
16. Participants unable to comply with the requirements of the protocol
17. Participants with any other significant medical or psychiatric conditions that in the opinion of the investigator would preclude participation in the trial
18. 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)

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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<br>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<br>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<br>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 Outcome Measures

Name	Time	Method
1. Comparison of mean salivary cortisone concentration post-Nasacthin and Synacthen administration, measured using LC-MS/MS at baseline and at 60 minutes post-drug administration.<br>2. Comparison of mean change from baseline in serum cortisol concentration post-Nasacthin and Synacthen administration, measured using LC-MS/MS at baseline and at 30 minutes post-drug administration.<br>3. 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.<br>4. 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.