Primary AldosteronismPUMPAPNCT06076473
Untargeted Metabolomics for Primary Aldosteronism
An observational study of Primary Aldosteronism, run by Liverpool University Hospitals NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
Primary aldosteronism (PA) is a common and likely under-diagnosed cause of secondary hypertension with associated cardiovascular morbidity and mortality. Current diagnosis comprises screening, confirmatory testing and sub-type classification (lateralisation) to distinguish unilateral disease (requiring surgery) from… Read more about this study
- Who is it for?
- Ages 18 to 120 yearsHealthy volunteers can take part
- Conditions the study is for
- Primary Aldosteronism
- What is being tested?
- Untargeted metabolomics
- How many people
- 40 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 19 Jan 2023to 19 Jan 2025
- Phase
- Observational
- 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 18 to 120 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Eligible participants will be undergoing diagnostic work-up for PA, meet the above eligibility criteria, and give informed consent to participate.
Who may be able to join
- Screening for PA to be performed in people with:
- sustained blood pressure (BP) above 150/100 mm Hg on each of three measurements obtained on different days, with hypertension (BP >140/90 mm Hg) resistant to three conventional antihypertensive drugs (including a diuretic), or controlled BP (<140/90 mm Hg) on four or more antihypertensive drugs.
- hypertension and spontaneous or diuretic-induced hypokalaemia.
- hypertension and adrenal incidentaloma.
- hypertension and sleep apnoea.
- hypertension and a family history of early onset hypertension or cerebrovascular accident at a young age (<40 years).
Show all 12Show fewer
- all hypertensive first-degree relatives of people with PA.
- Subset of people being screened for PA who are eligible for inclusion in this study:
- 18 years of age or older.
- People under the care of LUHFT.
- Able to give informed consent.
- Having lithium heparin plasma samples collected as part of their routine care.
Who cannot join
- Under 18 years of age.
- Unable to give informed consent.
- Insufficient clinical/biochemical/radiological/histological information to accurately assign patients to PA or non-PA subsets.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Liverpool University Hospitals NHS Foundation Trust
Liverpool, Merseyside, L9 7AL
Andrew Davison, 0151 525 5980, Andrew Davison <Andrew.Davison@liverpoolft.nhs.uk>
About this study
Official title: Pilot Untargeted Metabolomics for Primary Aldosteronism in Plasma (PUMPAP)
Primary aldosteronism (PA) is a common and likely under-diagnosed cause of secondary hypertension with associated cardiovascular morbidity and mortality. Current diagnosis comprises screening, confirmatory testing and sub-type classification (lateralisation) to distinguish unilateral disease (requiring surgery) from bilateral disease (requiring medical management). This multi-step process is complex and variable with a lack of uniformity in diagnostic protocols, standardised/reference assay methodologies, and diagnostic thresholds. There is evidence in the literature that targeted serum steroid panels may have a role in diagnosis of PA, and both targeted steroid panels and untargeted metabolomics in serum and urine are a promising area of research.
This study aims to identify and recruit participants (n=40; 20 with confirmed PA and 20 with other causes of hypertension) willing to donate lithium heparin plasma for a metabolomics pilot study. This plasma will be interrogated through untargeted metabolomics using gas/liquid chromatography-mass-spectrometric methods and computational data processing to allow power calculations and inform experimental design for future studies. The utility of metabolites from the metabolomics dataset will be evaluated by comparison against current biomarkers for screening, diagnosis and lateralisation as well as radiology and histology acquired through routine diagnostic work-up. The long-term aim for larger studies is to identify suitable candidate analytes in plasma for future development into targeted, clinically-useful analyte panels.
Read the detailed description
Participant Recruitment
- Suitable participants will be identified by members of their care teams, for whom screening, confirmatory testing and lateralisation will be / have been completed at LUHFT.
- Potential participants will be approached by a member of the study team seeking consent. Saline infusion testing and adrenal vein sampling are key points in the diagnostic work-up for participant recruitment for non-PA and PA cohorts, respectively.
- Consenting participants will have lithium heparin plasma collected and stored until the requisite sample size has been reached (n=40; 20 with PA and 20 with PA excluded by aldosterone:renin ratio at screening or saline infusion confirmatory testing). A lithium heparin tube will be used for routine renal profiles requested as part of saline infusion tests or adrenal vein sampling to avoid requirements for any additional blood tubes. The sample will be centrifuged and separated into two aliquots. One aliquot for metabolomic analysis at the University of Liverpool and one for storage within LUHFT until the end of the study (2 years) in case data validation is required. Clinical, biochemical, radiological and histological information from routine care will help to classify participants into PA (n=20) and non-PA (n=20) groups, as well as to assign lateralisation status. Ideally there will be equal representation from unilateral left, unilateral right and bilateral disease in the PA sub-set.
- Recruitment will close after 18 months.
Laboratory Analysis
- Untargeted metabolomics analysis using chromatography-mass spectrometric methods will be performed on lithium heparin plasma from all consenting participants. An aliquot of this sample will be transferred to the University of Liverpool for analysis and used to destruction (with no backwards transfer).
Data Analysis
- Computation analysis of the data set will be used to screen for novel PA biomarkers that could be further investigated in later studies.
- Univariate and multivariate methods will be applied. These will include univariate statistical and AUROC calculations, adjusted logistic regression techniques, unsupervised (clustering/visualisation) and supervised (classifier-based) multivariate methods
- Power calculations and pilot data set analysis will inform future experimental design.
Sample Storage
- Primary aliquots will be stored at LUHFT for up to 18 months awaiting analysis. They will then be transferred in one batch to the University of Liverpool and used to destruction.
- Secondary aliquots of biological material (which are intended as a back-up in case data validation is required) will be stored under appropriate conditions to preserve integrity until the end of the study. Samples will be disposed of after completion of the pilot study (2 years) in line with routine laboratory practice.
Data storage
- Storage of analytical and metadata will be for a period of five years. It will be stored on a secure computer on the Royal Liverpool University Hospital (RLUH) network.
- Conditions
- Primary Aldosteronism
- Being tested
- Untargeted metabolomics
- Keywords
- Pilot, Untargeted Metabolomics, Primary Aldosteronism, Plasma
- Medical subject headings
- Hyperaldosteronism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Untargeted metabolomicsDiagnostic test
Pilot untargeted plasma metabolomics aiming to identify novel biomarkers for PA diagnosis and subtyping, which could be compared against existing biomarkers and taken forward to larger future studies.
| Study group | Role | What they receive |
|---|---|---|
| Confirmed Primary Aldosteronism | Confirmed Primary Aldosteronism Receives: Diagnostic Test: Untargeted metabolomics | |
| Non-Primary Aldosteronism | Other causes of hypertension Receives: Diagnostic Test: Untargeted metabolomics |
What is being measured
The primary outcome is the main question the study is designed to answer.
Untargeted metabolomics
Identification of candidate biomarkers
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2023
- Study start19 Jan 2023
- Primary completion19 Jan 2025 (estimated)
- Study completion19 Jan 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary AldosteronismStudies 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
- Observational
- Observational model
- Other
- Time perspective
- Retrospective
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Liverpool University Hospitals NHS Foundation Trust
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Sarah Davies, MChem MSc, Principal investigator, Liverpool University Hospitals NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06076473
- Sponsor's protocol ID
- LHS001
- Acronym
- PUMPAP
- Status last verified
- Dec 2023
- First submitted
- 30 Dec 2022
- Last updated
- 15 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Patient identifiable data will not be shared outside the study team. Data will be pseudo-anonymised (mapped onto a unique study ID) by the study team to remove direct traceability to the participant and allow data to be shared between participating sites.
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Untargeted Metabolomics for Primary Aldosteronism in Plasma (PUMPAP)
- ClinicalTrials.gov ID
- NCT06076473
- Acronym / sponsor ID
- PUMPAP / LHS001
- Conditions
- Primary Aldosteronism
- Keywords
- Pilot, Untargeted Metabolomics, Primary Aldosteronism, Plasma
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Liverpool University Hospitals NHS Foundation TrustOther government
- Study start
- 19 Jan 2023 (actual)
- Primary completion
- 19 Jan 2025 (estimated)
- Study completion
- 19 Jan 2025 (estimated)
- First posted
- 10 Oct 2023 (actual)
- 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.
Primary aldosteronism (PA) is a common and likely under-diagnosed cause of secondary hypertension with associated cardiovascular morbidity and mortality. Current diagnosis comprises screening, confirmatory testing and sub-type classification (lateralisation) to distinguish unilateral disease (requiring surgery) from bilateral disease (requiring medical management). This multi-step process is complex and variable with a lack of uniformity in diagnostic protocols, standardised/reference assay methodologies, and diagnostic thresholds. There is evidence in the literature that targeted serum steroid panels may have a role in diagnosis of PA, and both targeted steroid panels and untargeted metabolomics in serum and urine are a promising area of research.
This study aims to identify and recruit participants (n=40; 20 with confirmed PA and 20 with other causes of hypertension) willing to donate lithium heparin plasma for a metabolomics pilot study. This plasma will be interrogated through untargeted metabolomics using gas/liquid chromatography-mass-spectrometric methods and computational data processing to allow power calculations and inform experimental design for future studies. The utility of metabolites from the metabolomics dataset will be evaluated by comparison against current biomarkers for screening, diagnosis and lateralisation as well as radiology and histology acquired through routine diagnostic work-up. The long-term aim for larger studies is to identify suitable candidate analytes in plasma for future development into targeted, clinically-useful analyte panels.
Detailed description
Participant Recruitment
- Suitable participants will be identified by members of their care teams, for whom screening, confirmatory testing and lateralisation will be / have been completed at LUHFT.
- Potential participants will be approached by a member of the study team seeking consent. Saline infusion testing and adrenal vein sampling are key points in the diagnostic work-up for participant recruitment for non-PA and PA cohorts, respectively.
- Consenting participants will have lithium heparin plasma collected and stored until the requisite sample size has been reached (n=40; 20 with PA and 20 with PA excluded by aldosterone:renin ratio at screening or saline infusion confirmatory testing). A lithium heparin tube will be used for routine renal profiles requested as part of saline infusion tests or adrenal vein sampling to avoid requirements for any additional blood tubes. The sample will be centrifuged and separated into two aliquots. One aliquot for metabolomic analysis at the University of Liverpool and one for storage within LUHFT until the end of the study (2 years) in case data validation is required. Clinical, biochemical, radiological and histological information from routine care will help to classify participants into PA (n=20) and non-PA (n=20) groups, as well as to assign lateralisation status. Ideally there will be equal representation from unilateral left, unilateral right and bilateral disease in the PA sub-set.
- Recruitment will close after 18 months.
Laboratory Analysis
- Untargeted metabolomics analysis using chromatography-mass spectrometric methods will be performed on lithium heparin plasma from all consenting participants. An aliquot of this sample will be transferred to the University of Liverpool for analysis and used to destruction (with no backwards transfer).
Data Analysis
- Computation analysis of the data set will be used to screen for novel PA biomarkers that could be further investigated in later studies.
- Univariate and multivariate methods will be applied. These will include univariate statistical and AUROC calculations, adjusted logistic regression techniques, unsupervised (clustering/visualisation) and supervised (classifier-based) multivariate methods
- Power calculations and pilot data set analysis will inform future experimental design.
Sample Storage
- Primary aliquots will be stored at LUHFT for up to 18 months awaiting analysis. They will then be transferred in one batch to the University of Liverpool and used to destruction.
- Secondary aliquots of biological material (which are intended as a back-up in case data validation is required) will be stored under appropriate conditions to preserve integrity until the end of the study. Samples will be disposed of after completion of the pilot study (2 years) in line with routine laboratory practice.
Data storage
- Storage of analytical and metadata will be for a period of five years. It will be stored on a secure computer on the Royal Liverpool University Hospital (RLUH) network.
Study design
- Observational model
- Other
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Confirmed Primary Aldosteronism | – | Diagnostic Test: Untargeted metabolomicsConfirmed Primary Aldosteronism |
| Non-Primary Aldosteronism | – | Diagnostic Test: Untargeted metabolomicsOther causes of hypertension |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Eligible participants will be undergoing diagnostic work-up for PA, meet the above eligibility criteria, and give informed consent to participate.
Key inclusion criteria (12 listed)
- sustained blood pressure (BP) above 150/100 mm Hg on each of three measurements obtained on different days, with hypertension (BP >140/90 mm Hg) resistant to three conventional antihypertensive drugs (including a diuretic), or controlled BP (<140/90 mm Hg) on four or more antihypertensive drugs.
- hypertension and spontaneous or diuretic-induced hypokalaemia.
- hypertension and adrenal incidentaloma.
- hypertension and sleep apnoea.
- hypertension and a family history of early onset hypertension or cerebrovascular accident at a young age (<40 years).
Key exclusion criteria (3 listed)
- Under 18 years of age.
- Unable to give informed consent.
- Insufficient clinical/biochemical/radiological/histological information to accurately assign patients to PA or non-PA subsets.
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 |
|---|---|---|
| Untargeted metabolomicsPilot untargeted plasma metabolomics aiming to identify novel biomarkers for PA diagnosis and subtyping, which could be compared against existing biomarkers and taken forward to larger future studies. | Diagnostic test | Confirmed Primary Aldosteronism, Non-Primary Aldosteronism |
Primary outcome
Untargeted metabolomics
Time frame: 2 years
Identification of candidate biomarkers
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2024.
- Individual participant dataSharing planned: No. Patient identifiable data will not be shared outside the study team. Data will be pseudo-anonymised (mapped onto a unique study ID) by the study team to remove direct traceability to the participant and allow data to be shared between participating sites.
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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.
Sarah Davies, MChem MSc principal investigator
Liverpool University Hospitals NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Primary Aldosteronism, run by Liverpool University Hospitals NHS Foundation 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 12 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 15 Feb 2024. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sarah Davies, MChem MSc (0151 706 4245, sarah.davies@liverpoolft.nhs.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Untargeted metabolomics (time frame: 2 years). 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 15 Feb 2024.