The Plasma Metabolomics Profiling of Primary Aldosteronism

Completed

• Conditions: Essential Hypertension; Primary Aldosteronism; Aldosterone-producing Adenoma; Idiopathic Aldosteronism
• Interventions: Diagnostic Test: liquid chromatography-mass spectrometry (LC/MS)

• Registration Number: NCT06500000
• Lead Sponsor: Third Military Medical University

Brief Summary

Primary aldosteronism (PA), characterized by overt renin-independent aldosterone production, is the most common form endocrine hypertension. Compared with blood pressure-matched cases of essential hypertension (EH), PA is associated with a higher risk of cardiovascular morbidity and mortality. It is estimated that PA affects at least 10% of hypertensive patients and up to 25% of treatment-resistant hypertension. The major subtypes of PA are comprised of bilateral idiopathic hyperaldosteronism (IHA) and unilateral aldosterone-producing adenoma (APA). The screening, confirmatory testing, and subtype differentiation of PA for therapeutic management is a multi-step and complex process, resulting in low screening rates and poor clinical recognition.

PA is an independent risk factor for metabolic morbidity. Metabolomic profiling is a relatively new strategy for the diagnosis and prognosis of disease through identification and quantification of various metabolites. In the current study, we aimed to investigate the potential biomakers for discriminating PA from EH, as well as subtype classification for PA, by untargeted metabolomics.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-08-15
• Primary Completion: 2022-12-28
• Study Completion: 2023-05-19
• Study First Submitted: 2024-06-30
• Status Verified: 2024-07
• Study First Submitted QC: 2024-07-07
• Last Update Submitted: 2024-07-07
• Study First Posted: 2024-07-15
• Last Update Posted: 2024-07-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 95

Inclusion Criteria

• According to 2010 Chinese guidelines for the management of Essential hypertension (EH), EH was defined as systolic blood pressure (SBP) ≥140 mm Hg, diastolic blood pressure (DBP) ≥90 mm Hg, and use of antihypertensive medicine within 2 weeks and excluded from PA through ARR or confirmatory testing.
• Patients were confirmed to be diagnosed with Primary aldosteronism (PA) in accordance with the Endocrine Society Clinical Practice Guideline criteria. Patients with an aldosterone-to-renin ratio (ARR) > 3.7 (ng/dL) further conformed with one of the following confirmatory tests: saline infusion test or captopril-inhibition test. Adrenal CT scans and Adrenal venous sampling (AVS) were performed for PA subtype classification.
• Patients with idiopathic hyperaldosteronism (IHA) were determined based on the absence of obvious adenoma on adrenal CT and bilateral aldosterone overproduction.
• Patients with aldosterone-producing adenoma (APA) were identified based on macroadenoma >1 cm on adrenal CT, unilateral hypersecretion of aldosterone, and pathological confirmation.
• Signed informed consent and agreed to participate in this study.

Exclusion Criteria

• other subtypes of secondary hypertension, including renal hypertension, renovascular hypertension, and adrenal hypertension (i.e., pheochromocytoma and Cushing syndrome).
• adrenal cortical carcinoma
• acute infection at the time of assessment
• severe cardiovascular or cerebrovascular disease, liver or renal dysfunction, tumors, autoimmune disease or mental disorders.
• history of adrenalectomy
• alcohol abuse or pregnancy

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
essential hypertension (EH)	liquid chromatography-mass spectrometry (LC/MS)	According to 2010 Chinese guidelines for the management of essential hypertension (EH), EH was defined as systolic BP (SBP) ≥140 mm Hg, diastolic BP (DBP) ≥90 mm Hg, and use of antihypertensive medicine within 2 weeks and excluded from PA through ARR or diagnostic testing.
aldosterone-producing adenoma (APA)	liquid chromatography-mass spectrometry (LC/MS)	Patients were confirmed to be diagnosed with primary aldosteronism (PA) in accordance with the Endocrine Society Clinical Practice Guideline criteria. Antihypertensive drugs that may affect the renin-angiotensin-aldosterone system (RAAS) were discontinued for at least 2-4 weeks. Patients with an aldosterone-to-renin ratio (ARR) \> 3.7 (ng/dL) further underwent one of the following confirmatory tests: saline infusion test (infusion of 2 L isotonic saline within 4 h) or captopril-inhibition test (oral administration of 50 mg captopril). Adrenal CT scan and adrenal vein sampling (AVS) were performed for PA subtype classification. Patients with APA were identified based on macroadenoma \>1 cm on adrenal CT, unilateral hypersecretion of aldosterone, and pathological confirmation.
idiopathic aldosteronism (IHA)	liquid chromatography-mass spectrometry (LC/MS)	Patients were confirmed to be diagnosed with primary aldosteronism (PA) in accordance with the Endocrine Society Clinical Practice Guideline criteria. Antihypertensive drugs that may affect the renin-angiotensin-aldosterone system (RAAS) were discontinued for at least 2-4 weeks. Patients with an aldosterone-to-renin ratio (ARR) \> 3.7 (ng/dL) further underwent one of the following confirmatory tests: saline infusion test (infusion of 2 L isotonic saline within 4 h) or captopril-inhibition test (oral administration of 50 mg captopril). Adrenal CT scan and adrenal vein sampling (AVS) were performed for PA subtype classification. Patients with IHA were determined based on the absence of obvious adenoma on adrenal CT and bilateral aldosterone overproduction.

Primary Outcome Measures

Name	Time	Method
The potential biomarkers for primary aldosteronism diagnosis via untargeted metabolomics	4 months	The differentially expressed metabolites between primary aldosteronism (PA) and essential hypertension (EH) will be identified by untargeted metabolomics. The differentially expressed metabolites with good discriminative capability for determination of PA from EH can serve as biomarkers for PA diagnosis.
The predictive models for PA diagnosis and subtype classification by machine learning	4 months	The predictive models will be constructed through the application of machine learning, integrating clinical data with differentially expressed metabolites for the diagnosis and subtype classification of PA
The potential biomarkers for primary aldosteronism subtype classification via untargeted metabolomics	4 months	The differentially expressed metabolites between idiopathic aldosteronism (IHA) and aldosterone-producing adenoma (APA) will be identified by untargeted metabolomics. The differentially expressed metabolites with good discriminative capability for determination of APA from IHA can serve as biomarkers for PA subtype classification.

Trial Locations

Locations (1)

China Chongqing The third hospital affiliated to the Third Millitary Medical University; 🇨🇳 Chongqing, Chongqing, China