Ignite Creation Date:
2024-05-06 @ 9:14 AM
Last Modification Date:
2024-10-26 @ 12:12 PM
Study NCT ID:
NCT02939144
Status:
COMPLETED
Last Update Posted:
2019-04-11
First Post:
2016-10-18
Brief Title:
An Investigation Into the Effect of Liquorice Ingestion on the Salivary Cortisol to Cortisone Molar Ratio
Sponsor:
The Royal Wolverhampton Hospitals NHS Trust
Organization:
The Royal Wolverhampton Hospitals NHS Trust
Study Overview
Official Title:
An Investigation Into the Effect of Liquorice Ingestion on the Salivary Cortisol to Cortisone Molar Ratio
Status:
COMPLETED
Status Verified Date:
2019-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Aldosterone the major mineralocorticoid hormone and cortisol the major glucocorticoid hormone are produced in the adrenal gland Aldosterone binds intracellular mineralocorticoid receptors MR in the kidney promoting urinary reabsorption of sodium and water and excretion of potassium and hydrogen ions Unregulated mineralocorticoid excess may therefore lead to high blood pressure due to sodium and water retention and hypokalaemic alkalosis
Blood concentrations of cortisol which has equal affinity for MR are 1000fold greater than those of aldosterone Therefore in order not to overwhelm MR cortisol needs to be inactivated before it binds MR This is achieved by the enzyme 11-betahydroxysteroid dehydrogenase type 2 11ßHSD-2 in the kidney which rapidly inactivates cortisol to cortisone this process allows only aldosterone to bind MR Reduced activity of 11ßHSD-2 leads to an accumulation of cortisol which binds MR and hence has the effect of aldosterone Reduced activity of 11ßHSD-2 may be seen in the inherited condition of Apparent mineralocorticoid excess AME or in excessive liquorice ingestion The diagnosis of AME and liquorice toxicity is difficult due to unavailability of diagnostic urine analysis in most general laboratories Cortisol in the salivary glands similarly to that in kidneys is metabolised by 11β-HSD2 to cortisone It is proposed that increased salivary cortisolcortisone ratio could offer a simple and convenient diagnostic test for AME and liquorice toxicity and can be used as a surrogate marker of urinary cortisolcortisone ratio The advantages of salivary cortisolcortisone include non-invasiveness making it stress free for the patient no risk of needle stick injury and ease of collection allowing potential home testing and posting of samples
Blood concentrations of cortisol which has equal affinity for MR are 1000fold greater than those of aldosterone Therefore in order not to overwhelm MR cortisol needs to be inactivated before it binds MR This is achieved by the enzyme 11-betahydroxysteroid dehydrogenase type 2 11ßHSD-2 in the kidney which rapidly inactivates cortisol to cortisone this process allows only aldosterone to bind MR Reduced activity of 11ßHSD-2 leads to an accumulation of cortisol which binds MR and hence has the effect of aldosterone Reduced activity of 11ßHSD-2 may be seen in the inherited condition of Apparent mineralocorticoid excess AME or in excessive liquorice ingestion The diagnosis of AME and liquorice toxicity is difficult due to unavailability of diagnostic urine analysis in most general laboratories Cortisol in the salivary glands similarly to that in kidneys is metabolised by 11β-HSD2 to cortisone It is proposed that increased salivary cortisolcortisone ratio could offer a simple and convenient diagnostic test for AME and liquorice toxicity and can be used as a surrogate marker of urinary cortisolcortisone ratio The advantages of salivary cortisolcortisone include non-invasiveness making it stress free for the patient no risk of needle stick injury and ease of collection allowing potential home testing and posting of samples
Detailed Description:
Twelve healthy normotensive individuals between 20-65 years old without high blood pressure will be recruited to the study Study individuals will be recruited among the hospital staff on a voluntary basis
The study period will consist of three phases prior to which potential volunteers will be identified
Phase 1 Run-in week with definition of baseline values
Phase 2 Six day period with a daily intake of 550 mg of Glycyrrhizin for 5 days in the form of liquorice confectionary
Phase 3 Two week washout period
Phase 1 The run-in week
Potential volunteers will be identified and given study information participant information sheet allowing time to consider taking part Most volunteers to be recruited among the hospital staff
Written consent will be obtained from volunteers by study investigators
Volunteers will have their blood pressure weight and height checked and will be assessed for inclusion and exclusion criteria
The office blood pressure will be measured after 5 min rest Blood pressure will be measured on two different days during the run-in period twice each time and the mean of these four measurements will be used as the baseline value
Baseline samples taken any day within the run-in week days -6 -5 -4 -3-2-1 0
Saliva samples on two consecutive days between 0830h to 0930h
One blood sample between 0830h to 0930h
One 24h urine sample
Phase 2 A six day study period days 1 2 3 4 5 6
Twelve volunteers will ingest confectionary liquorice containing 550 mg of Glycyrrhizin in divided amounts each day for five days The liquorice in the form of sugar-free candies will be ingested three times per day at least 30 minutes prior to meals in the morning afternoon and evening
Volunteers will be requested to refrain from eating grapefruit or drinking grapefruit juice during the study period
The liquorice candies will be weighed to give the correct dose of glycyrrhizin
Subjects will be clinically monitored daily during liquorice consumption for any potential side effects including headaches swelling dyspepsia dizziness joint pain muscle aches and palpitations
Office blood pressure heart rate and weight will be measured daily during liquorice consumption
Volunteers will collect salivary samples daily between 0830h to 0930h for six days
A blood sample will be collected on day 6 between 830h to 0930h
A 24h urine sample will then be collected on starting at 830h to 0930h and completed on 830h to 0930h on day 7
Phase 3 At the end of a two week washout period Day 19
Salivary and blood samples will be collected between 0830h to 0930h
A 24h urine sample will then be collected starting at 830h to 0930h on day 19 and completed on 830h to 0930h on day 20
Office blood pressure pulse rate and weight will recorded
In total 40 mls of saliva 30 mls blood and three 24h urine samples will be collected Labelling of saliva blood and urine samples will be anonymized Saliva and blood samples will be centrifuged The separated serumplasma and extracted saliva will be kept frozen at -80oC until analysed in one batch to minimise analytical variation 24h urine samples will have their volume measured and an aliquot will be kept frozen at -80oC until analysed in one batch
The study period will consist of three phases prior to which potential volunteers will be identified
Phase 1 Run-in week with definition of baseline values
Phase 2 Six day period with a daily intake of 550 mg of Glycyrrhizin for 5 days in the form of liquorice confectionary
Phase 3 Two week washout period
Phase 1 The run-in week
Potential volunteers will be identified and given study information participant information sheet allowing time to consider taking part Most volunteers to be recruited among the hospital staff
Written consent will be obtained from volunteers by study investigators
Volunteers will have their blood pressure weight and height checked and will be assessed for inclusion and exclusion criteria
The office blood pressure will be measured after 5 min rest Blood pressure will be measured on two different days during the run-in period twice each time and the mean of these four measurements will be used as the baseline value
Baseline samples taken any day within the run-in week days -6 -5 -4 -3-2-1 0
Saliva samples on two consecutive days between 0830h to 0930h
One blood sample between 0830h to 0930h
One 24h urine sample
Phase 2 A six day study period days 1 2 3 4 5 6
Twelve volunteers will ingest confectionary liquorice containing 550 mg of Glycyrrhizin in divided amounts each day for five days The liquorice in the form of sugar-free candies will be ingested three times per day at least 30 minutes prior to meals in the morning afternoon and evening
Volunteers will be requested to refrain from eating grapefruit or drinking grapefruit juice during the study period
The liquorice candies will be weighed to give the correct dose of glycyrrhizin
Subjects will be clinically monitored daily during liquorice consumption for any potential side effects including headaches swelling dyspepsia dizziness joint pain muscle aches and palpitations
Office blood pressure heart rate and weight will be measured daily during liquorice consumption
Volunteers will collect salivary samples daily between 0830h to 0930h for six days
A blood sample will be collected on day 6 between 830h to 0930h
A 24h urine sample will then be collected on starting at 830h to 0930h and completed on 830h to 0930h on day 7
Phase 3 At the end of a two week washout period Day 19
Salivary and blood samples will be collected between 0830h to 0930h
A 24h urine sample will then be collected starting at 830h to 0930h on day 19 and completed on 830h to 0930h on day 20
Office blood pressure pulse rate and weight will recorded
In total 40 mls of saliva 30 mls blood and three 24h urine samples will be collected Labelling of saliva blood and urine samples will be anonymized Saliva and blood samples will be centrifuged The separated serumplasma and extracted saliva will be kept frozen at -80oC until analysed in one batch to minimise analytical variation 24h urine samples will have their volume measured and an aliquot will be kept frozen at -80oC until analysed in one batch
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None