Apparent Mineralocorticoid ExcessNCT02939144
An Investigation Into the Effect of Liquorice Ingestion on the Salivary Cortisol to Cortisone Molar Ratio
A study testing Liquorice in people with Apparent Mineralocorticoid Excess, run by The Royal Wolverhampton Hospitals NHS Trust at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Apparent Mineralocorticoid Excess
- What is being tested?
- Liquorice
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Nov 2016to 6 Mar 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Normal blood pressure without electrolyte abnormalities.
- Healthy, without any known medical conditions or treatment other than the contraceptive pill.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
The Royal Wolverhampton NHS Trust
Wolverhampton, West Midlands, WV10 0QP
About this study
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.
Read the 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 08.30h to 09.30h.
- One blood sample between 08.30h to 09.30h.
- 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 08.30h to 09.30h for six days.
- A blood sample will be collected on day 6 between 8.30h to 09.30h.
- A 24h urine sample will then be collected on starting at 8.30h to 09.30h and completed on 8.30h to 09.30h on day 7.
Phase 3: At the end of a two week washout period (Day 19):
- Salivary and blood samples will be collected between 08.30h to 09.30h
- A 24h urine sample will then be collected starting at 8.30h to 09.30h on day 19 and completed on 8.30h to 09.30h 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 serum/plasma 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.
- Conditions
- Apparent Mineralocorticoid Excess
- Being tested
- Liquorice
- Medical subject headings
- Mineralocorticoid Excess Syndrome, Apparent
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LiquoriceDietary 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).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Dietary Supplement: Liquorice |
What is being measured
The primary outcome is the main question the study is designed to answer.
salivary cortisol/cortisone ratio induced by liquorice (glycyrrhetinic acid and its metabolites) ingestion
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2016 (estimated)
- Study startNov 2016
- Primary completion6 Mar 2017
- Study completion6 Mar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Apparent Mineralocorticoid ExcessStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Royal Wolverhampton Hospitals NHS Trust
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Rousseau Gama, Principal investigator, The Royal Wolverhampton NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02939144
- Sponsor's protocol ID
- 2016LAB86
- Status last verified
- Apr 2019
- First submitted
- 18 Oct 2016
- Last updated
- 11 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Investigation Into the Effect of Liquorice Ingestion on the Salivary Cortisol to Cortisone Molar Ratio
- ClinicalTrials.gov ID
- NCT02939144
- Acronym / sponsor ID
- 2016LAB86
- Conditions
- Apparent Mineralocorticoid Excess
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- The Royal Wolverhampton Hospitals NHS TrustOther government
- Study start
- Nov 2016 (actual)
- Primary completion
- 6 Mar 2017 (actual)
- Study completion
- 6 Mar 2017 (actual)
- First posted
- 19 Oct 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 08.30h to 09.30h.
- One blood sample between 08.30h to 09.30h.
- 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 08.30h to 09.30h for six days.
- A blood sample will be collected on day 6 between 8.30h to 09.30h.
- A 24h urine sample will then be collected on starting at 8.30h to 09.30h and completed on 8.30h to 09.30h on day 7.
Phase 3: At the end of a two week washout period (Day 19):
- Salivary and blood samples will be collected between 08.30h to 09.30h
- A 24h urine sample will then be collected starting at 8.30h to 09.30h on day 19 and completed on 8.30h to 09.30h 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 serum/plasma 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 design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Liquorice | Experimental | Dietary Supplement: LiquoriceParticipants 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. |
Who may qualify
- Ages
- 20 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Normal blood pressure without electrolyte abnormalities.
- Healthy, without any known medical conditions or treatment other than the contraceptive pill.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LiquoriceLiquorice 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). | Dietary supplement | Liquorice |
Primary outcome
salivary cortisol/cortisone ratio induced by liquorice (glycyrrhetinic acid and its metabolites) ingestion
Time frame: 4 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rousseau Gama principal investigator
The Royal Wolverhampton NHS Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Liquorice in people with Apparent Mineralocorticoid Excess, run by The Royal Wolverhampton Hospitals NHS Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
salivary cortisol/cortisone ratio induced by liquorice (glycyrrhetinic acid and its metabolites) ingestion (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Apr 2019.