Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT06076473
Other study ID # LHS001
Secondary ID
Status Recruiting
Phase
First received
Last updated
Start date January 19, 2023
Est. completion date January 19, 2025

Study information

Verified date December 2023
Source Liverpool University Hospitals NHS Foundation Trust
Contact Sarah Davies, MChem MSc
Phone 0151 706 4245
Email sarah.davies@liverpoolft.nhs.uk
Is FDA regulated No
Health authority
Study type Observational

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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 40
Est. completion date January 19, 2025
Est. primary completion date January 19, 2025
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 18 Years to 120 Years
Eligibility Inclusion Criteria: 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). - 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. Exclusion Criteria: - 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.

Study Design


Related Conditions & MeSH terms


Intervention

Diagnostic Test:
Untargeted metabolomics
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.

Locations

Country Name City State
United Kingdom Liverpool University Hospitals NHS Foundation Trust Liverpool Merseyside

Sponsors (1)

Lead Sponsor Collaborator
Liverpool University Hospitals NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Untargeted metabolomics Identification of candidate biomarkers 2 years
See also
  Status Clinical Trial Phase
Completed NCT02885662 - Study of CS-3150 in Patients With Primary Aldosteronism N/A
Withdrawn NCT02096939 - Microvascular Function in Primary Aldosteronism N/A
Completed NCT01728493 - Primary Aldosteronism in General Practice: Organ Damage, Epidemiology and Treatment N/A
Recruiting NCT06228677 - Comparison of Catecholamine Concentrations in Venous Blood During Selective Adrenal Artery Embolization
Recruiting NCT06047912 - Screening for Primary Aldosteronism in Hypertension With 24-hour URinary aLdosterone
Recruiting NCT04991961 - Effect of Anti-hypertensive Medications on the Diagnostic Accuracy in Screening for Primary Aldosteronism
Recruiting NCT05405101 - Randomised Trial Comparing Thermal Ablation With Adrenalectomy in the Treatment of Unilateral Asymmetric PA N/A
Recruiting NCT05501080 - The Effect of SAAE on Ventricular Remodeling in PA Patients N/A
Recruiting NCT05973604 - Prevalence of Primary Aldosteronism in Atrial Fibrillation
Recruiting NCT05826080 - Effect of Adrenocorticotropic Hormone Stimulation During Adrenal Vein Sampling in Primary Aldosteronism
Completed NCT04179019 - Calcium Channel Blockade in Primary Aldosteronism Phase 2
Completed NCT03500120 - Diagnostic Accuracy of Seated Saline Suppression Test for Primary Aldosteronism
Recruiting NCT04213963 - Prospective Study on Primary Aldosteronism in Resistant Hypertension
Completed NCT05435703 - Renal Cysts and Primary Aldosteronism
Recruiting NCT02945904 - IS Metomidate PET-CT Superior to Adrenal Venous Sampling in Predicting Outcome From Adrenalectomy in Patients With Primary Hyperaldosteronism
Enrolling by invitation NCT02257450 - Primary Aldosteronism in Malaysia: A Nationwide Multicentre Study N/A
Recruiting NCT05561361 - The Effect of SAAE on Vascular Endothelial Function in PA Patients
Completed NCT03398785 - Adrenal Artery Ablation Treats Primary Aldosteronism Phase 3
Recruiting NCT03224312 - Chongqing Primary Aldosteronism Study
Recruiting NCT04428827 - Outcome of Patients With Primary Aldosteronism