Untargeted Metabolomics for Primary Aldosteronism — PUMPAP  

Primary Aldosteronism Clinical Trial

Official title: Pilot Untargeted Metabolomics for Primary Aldosteronism in Plasma (PUMPAP)

Status Recruiting

Clinical 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 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Hyperaldosteronism
• Primary Aldosteronism

• NCT number: NCT06076473
• Study type: Observational
• Source: Liverpool University Hospitals NHS Foundation Trust
• Contact: Sarah Davies, MChem MSc
• Phone: 0151 706 4245
• Email: sarah.davies@liverpoolft.nhs.uk
• Status: Recruiting
• Start date: January 19, 2023
• Completion date: January 19, 2025