Randomised, placebo-controlled, double-blinded, four-way crossover trial to demonstrate the comparative pharmacodynamic equivalence of a non-invasive diagnostic test for adrenal insufficiency in a healthy population: the STARLIT-2 study protocol
Introduction Cortisol is an essential stress hormone and failure of its production, known as adrenal insufficiency (AI), is associated with significant mortality due to adrenal crisis. The Short Synacthen Test (SST) is the current diagnostic test of choice for AI, but it is both invasive and resourc...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2024-12-01
|
| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/14/12/e094830.full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841536658134007808 |
|---|---|
| author | Judith Cohen Miguel Debono Kathleen Baster Richard J Ross Charlotte J Elder Kathryn L Date Sharon L Caunt Jane Fearnside Trevor N Johnson Rosie N Taylor |
| author_facet | Judith Cohen Miguel Debono Kathleen Baster Richard J Ross Charlotte J Elder Kathryn L Date Sharon L Caunt Jane Fearnside Trevor N Johnson Rosie N Taylor |
| author_sort | Judith Cohen |
| collection | DOAJ |
| description | Introduction Cortisol is an essential stress hormone and failure of its production, known as adrenal insufficiency (AI), is associated with significant mortality due to adrenal crisis. The Short Synacthen Test (SST) is the current diagnostic test of choice for AI, but it is both invasive and resource intensive. Globally, there is an unmet need for a non-invasive, cost-effective test. A novel formulation, Nasacthin, has been developed, which can be delivered intranasally, with the resultant glucocorticoid levels measured in saliva instead of blood. The Salivary Test of Adrenal Response to Liquid Intranasal Tetracosactide (STARLIT-2) study aims to clinically validate the Nasacthin test in healthy volunteers.Methods and analysis STARLIT-2 is a randomised, placebo-controlled, double-blinded, four-way crossover trial. 32 healthy adults and children will be randomised to receive each of four study drugs (Synacthen, Nasacthin and their respective placebos) over four study visits (one per visit). Paired blood and saliva samples will be collected from participants at baseline, and then at 30, 60, 90 and 120 min after drug administration. Additional salivary samples will be collected at 180, 240, 360 and 480 min after drug administration. The primary outcome measures are to compare the mean serum cortisol at 30 min after Synacthen or Nasacthin dose, with a view to determine non-inferiority; and to compare the mean change from baseline in serum cortisol at 30 min after active and placebo doses of both Synacthen and Nasacthin, aiming to demonstrate superiority of active over placebo. In addition, the proportion of participants for which Nasacthin produces a rise above a preset serum cortisol threshold at 30 min will be determined, with the negative per cent agreement with the SST calculated using the SST as the reference standard.Ethics and dissemination The study and its amendments have been reviewed and approved by South Central–Hampshire A Research Ethics Committee. Results will be disseminated in peer-reviewed journals and conference presentations, and feedback to trial participants will be facilitated following consultation with patient and public involvement and engagement groups.Trial registration number ISRCTN62724177 |
| format | Article |
| id | doaj-art-46fcc5d301fc4e60b3c2b7ec54955edf |
| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj-art-46fcc5d301fc4e60b3c2b7ec54955edf2025-01-14T12:00:16ZengBMJ Publishing GroupBMJ Open2044-60552024-12-01141210.1136/bmjopen-2024-094830Randomised, placebo-controlled, double-blinded, four-way crossover trial to demonstrate the comparative pharmacodynamic equivalence of a non-invasive diagnostic test for adrenal insufficiency in a healthy population: the STARLIT-2 study protocolJudith Cohen0Miguel Debono1Kathleen Baster2Richard J Ross3Charlotte J Elder4Kathryn L Date5Sharon L Caunt6Jane Fearnside7Trevor N Johnson8Rosie N Taylor91 Hull Health Trials Unit, University of Hull, Hull, UK3 Academic Directorate of Diabetes and Endocrinology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK2 Statistical Services Unit, The University of Sheffield, Sheffield, UK6 Clinical Medicine, School of Medicine and Population Health, The University of Sheffield, Sheffield, UK6 Clinical Medicine, School of Medicine and Population Health, The University of Sheffield, Sheffield, UK1 Hull Health Trials Unit, University of Hull, Hull, UK3 Academic Directorate of Diabetes and Endocrinology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK4 Sheffield Centre for Health and Related Research (SCHARR), School of Medicine and Population Health, The University of Sheffield, Sheffield, UK5 Translational Sciences Group, Certara UK Limited, Sheffield, UK2 Statistical Services Unit, The University of Sheffield, Sheffield, UKIntroduction Cortisol is an essential stress hormone and failure of its production, known as adrenal insufficiency (AI), is associated with significant mortality due to adrenal crisis. The Short Synacthen Test (SST) is the current diagnostic test of choice for AI, but it is both invasive and resource intensive. Globally, there is an unmet need for a non-invasive, cost-effective test. A novel formulation, Nasacthin, has been developed, which can be delivered intranasally, with the resultant glucocorticoid levels measured in saliva instead of blood. The Salivary Test of Adrenal Response to Liquid Intranasal Tetracosactide (STARLIT-2) study aims to clinically validate the Nasacthin test in healthy volunteers.Methods and analysis STARLIT-2 is a randomised, placebo-controlled, double-blinded, four-way crossover trial. 32 healthy adults and children will be randomised to receive each of four study drugs (Synacthen, Nasacthin and their respective placebos) over four study visits (one per visit). Paired blood and saliva samples will be collected from participants at baseline, and then at 30, 60, 90 and 120 min after drug administration. Additional salivary samples will be collected at 180, 240, 360 and 480 min after drug administration. The primary outcome measures are to compare the mean serum cortisol at 30 min after Synacthen or Nasacthin dose, with a view to determine non-inferiority; and to compare the mean change from baseline in serum cortisol at 30 min after active and placebo doses of both Synacthen and Nasacthin, aiming to demonstrate superiority of active over placebo. In addition, the proportion of participants for which Nasacthin produces a rise above a preset serum cortisol threshold at 30 min will be determined, with the negative per cent agreement with the SST calculated using the SST as the reference standard.Ethics and dissemination The study and its amendments have been reviewed and approved by South Central–Hampshire A Research Ethics Committee. Results will be disseminated in peer-reviewed journals and conference presentations, and feedback to trial participants will be facilitated following consultation with patient and public involvement and engagement groups.Trial registration number ISRCTN62724177https://bmjopen.bmj.com/content/14/12/e094830.full |
| spellingShingle | Judith Cohen Miguel Debono Kathleen Baster Richard J Ross Charlotte J Elder Kathryn L Date Sharon L Caunt Jane Fearnside Trevor N Johnson Rosie N Taylor Randomised, placebo-controlled, double-blinded, four-way crossover trial to demonstrate the comparative pharmacodynamic equivalence of a non-invasive diagnostic test for adrenal insufficiency in a healthy population: the STARLIT-2 study protocol BMJ Open |
| title | Randomised, placebo-controlled, double-blinded, four-way crossover trial to demonstrate the comparative pharmacodynamic equivalence of a non-invasive diagnostic test for adrenal insufficiency in a healthy population: the STARLIT-2 study protocol |
| title_full | Randomised, placebo-controlled, double-blinded, four-way crossover trial to demonstrate the comparative pharmacodynamic equivalence of a non-invasive diagnostic test for adrenal insufficiency in a healthy population: the STARLIT-2 study protocol |
| title_fullStr | Randomised, placebo-controlled, double-blinded, four-way crossover trial to demonstrate the comparative pharmacodynamic equivalence of a non-invasive diagnostic test for adrenal insufficiency in a healthy population: the STARLIT-2 study protocol |
| title_full_unstemmed | Randomised, placebo-controlled, double-blinded, four-way crossover trial to demonstrate the comparative pharmacodynamic equivalence of a non-invasive diagnostic test for adrenal insufficiency in a healthy population: the STARLIT-2 study protocol |
| title_short | Randomised, placebo-controlled, double-blinded, four-way crossover trial to demonstrate the comparative pharmacodynamic equivalence of a non-invasive diagnostic test for adrenal insufficiency in a healthy population: the STARLIT-2 study protocol |
| title_sort | randomised placebo controlled double blinded four way crossover trial to demonstrate the comparative pharmacodynamic equivalence of a non invasive diagnostic test for adrenal insufficiency in a healthy population the starlit 2 study protocol |
| url | https://bmjopen.bmj.com/content/14/12/e094830.full |
| work_keys_str_mv | AT judithcohen randomisedplacebocontrolleddoubleblindedfourwaycrossovertrialtodemonstratethecomparativepharmacodynamicequivalenceofanoninvasivediagnostictestforadrenalinsufficiencyinahealthypopulationthestarlit2studyprotocol AT migueldebono randomisedplacebocontrolleddoubleblindedfourwaycrossovertrialtodemonstratethecomparativepharmacodynamicequivalenceofanoninvasivediagnostictestforadrenalinsufficiencyinahealthypopulationthestarlit2studyprotocol AT kathleenbaster randomisedplacebocontrolleddoubleblindedfourwaycrossovertrialtodemonstratethecomparativepharmacodynamicequivalenceofanoninvasivediagnostictestforadrenalinsufficiencyinahealthypopulationthestarlit2studyprotocol AT richardjross randomisedplacebocontrolleddoubleblindedfourwaycrossovertrialtodemonstratethecomparativepharmacodynamicequivalenceofanoninvasivediagnostictestforadrenalinsufficiencyinahealthypopulationthestarlit2studyprotocol AT charlottejelder randomisedplacebocontrolleddoubleblindedfourwaycrossovertrialtodemonstratethecomparativepharmacodynamicequivalenceofanoninvasivediagnostictestforadrenalinsufficiencyinahealthypopulationthestarlit2studyprotocol AT kathrynldate randomisedplacebocontrolleddoubleblindedfourwaycrossovertrialtodemonstratethecomparativepharmacodynamicequivalenceofanoninvasivediagnostictestforadrenalinsufficiencyinahealthypopulationthestarlit2studyprotocol AT sharonlcaunt randomisedplacebocontrolleddoubleblindedfourwaycrossovertrialtodemonstratethecomparativepharmacodynamicequivalenceofanoninvasivediagnostictestforadrenalinsufficiencyinahealthypopulationthestarlit2studyprotocol AT janefearnside randomisedplacebocontrolleddoubleblindedfourwaycrossovertrialtodemonstratethecomparativepharmacodynamicequivalenceofanoninvasivediagnostictestforadrenalinsufficiencyinahealthypopulationthestarlit2studyprotocol AT trevornjohnson randomisedplacebocontrolleddoubleblindedfourwaycrossovertrialtodemonstratethecomparativepharmacodynamicequivalenceofanoninvasivediagnostictestforadrenalinsufficiencyinahealthypopulationthestarlit2studyprotocol AT rosientaylor randomisedplacebocontrolleddoubleblindedfourwaycrossovertrialtodemonstratethecomparativepharmacodynamicequivalenceofanoninvasivediagnostictestforadrenalinsufficiencyinahealthypopulationthestarlit2studyprotocol |