An Investigation Into the Effect of Liquorice Ingestion on the Salivary Cortisol to Cortisone Molar Ratio

NCT02939144 | Completed

• 1 other identifier: 2016LAB86
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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 cortisol/cortisone ratio could offer a simple and convenient diagnostic test for AME and liquorice toxicity and can be used as a surrogate marker of urinary cortisol/cortisone ratio. The advantages of salivary cortisol/cortisone 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.

Conditions

Apparent Mineralocorticoid Excess

Outcome Measures

Primary Outcomes (1)

• salivary cortisol/cortisone ratio induced by liquorice (glycyrrhetinic acid and its metabolites) ingestion

  4 weeks

Study Arms (1)

Liquorice

EXPERIMENTAL

Participants of the single-arm study will ingest liquorice candy and their blood, saliva and urine samples will be collected. They will be regularly monitored for any potential side effects.

Dietary Supplement: Liquorice

Interventions

Liquorice DIETARY_SUPPLEMENT

Liquorice ingestion will mimic the inherited condition of 'Apparent mineralocorticoid excess (AME)by showing the effects of the reduced activity of 11ßHSD-2 (which leads to an accumulation of cortisol which binds MR and hence has the effect of aldosterone).

Liquorice

Eligibility Criteria

• Age: 20 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Normal blood pressure without electrolyte abnormalities.
• Healthy, without any known medical conditions or treatment other than the contraceptive pill.

You may not qualify if:

• Pregnant women.
• Subjects with learning disability or those lacking mental capacity to give consent.
• On prescribed and over-the-counter medication and herbal remedies excluding the contraceptive pill.
• Any known medical condition.
• Subjects with difficult blood access.
• Subjects with dental disease.
• Those using tobacco in any form.

Sponsors & Collaborators

• The Royal Wolverhampton Hospitals NHS Trust: lead

Study Sites (1)

The Royal Wolverhampton NHS Trust

Wolverhampton, West Midlands, WV10 0QP, United Kingdom

Location

MeSH Terms

Conditions

Mineralocorticoid Excess Syndrome, Apparent

Interventions

Glycyrrhiza glabra extract

Condition Hierarchy (Ancestors)

Steroid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Rousseau Gama

  The Royal Wolverhampton NHS Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2016
• First Posted: October 19, 2016
• Study Start: November 1, 2016
• Primary Completion: March 6, 2017
• Study Completion: March 6, 2017
• Last Updated: April 11, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)