The Plasma Metabolomics Profiling of Primary Aldosteronism

NCT ID: NCT06500000

Last Updated: 2024-07-15

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 95 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-08-15
• Study Completion Date: 2023-05-19

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.

Conditions

Primary Aldosteronism; Essential Hypertension; Idiopathic Aldosteronism; Aldosterone-producing Adenoma

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

essential hypertension (EH)

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.

liquid chromatography-mass spectrometry (LC/MS)

Intervention Type: DIAGNOSTIC_TEST

Metabolomics is a rapidly evolving high-throughput technology that allows the measurement of the entire complement of metabolites generated by biochemical reactions under certain conditions in biological fluids or tissues. This technology has been used extensively to identify biomarkers in various cancers, nervous system diseases, cardiovascular diseases, pituitary diseases, and other diseases. The identification of biomarkers can be clinically useful for a more accurate diagnosis, prognosis, and treatment choice as well as disease monitoring. Among mass spectrometry (MS) methods, liquid chromatography- mass spectrometry (LC-MS) has been recognized as a robust metabolomics tool and has been widely applied in metabolite identification and quantification due to its high sensitivity, peak resolution, and reproducibility.

idiopathic aldosteronism (IHA)

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.

liquid chromatography-mass spectrometry (LC/MS)

Intervention Type: DIAGNOSTIC_TEST

Metabolomics is a rapidly evolving high-throughput technology that allows the measurement of the entire complement of metabolites generated by biochemical reactions under certain conditions in biological fluids or tissues. This technology has been used extensively to identify biomarkers in various cancers, nervous system diseases, cardiovascular diseases, pituitary diseases, and other diseases. The identification of biomarkers can be clinically useful for a more accurate diagnosis, prognosis, and treatment choice as well as disease monitoring. Among mass spectrometry (MS) methods, liquid chromatography- mass spectrometry (LC-MS) has been recognized as a robust metabolomics tool and has been widely applied in metabolite identification and quantification due to its high sensitivity, peak resolution, and reproducibility.

aldosterone-producing adenoma (APA)

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.

liquid chromatography-mass spectrometry (LC/MS)

Intervention Type: DIAGNOSTIC_TEST

Metabolomics is a rapidly evolving high-throughput technology that allows the measurement of the entire complement of metabolites generated by biochemical reactions under certain conditions in biological fluids or tissues. This technology has been used extensively to identify biomarkers in various cancers, nervous system diseases, cardiovascular diseases, pituitary diseases, and other diseases. The identification of biomarkers can be clinically useful for a more accurate diagnosis, prognosis, and treatment choice as well as disease monitoring. Among mass spectrometry (MS) methods, liquid chromatography- mass spectrometry (LC-MS) has been recognized as a robust metabolomics tool and has been widely applied in metabolite identification and quantification due to its high sensitivity, peak resolution, and reproducibility.

Interventions

liquid chromatography-mass spectrometry (LC/MS)

Metabolomics is a rapidly evolving high-throughput technology that allows the measurement of the entire complement of metabolites generated by biochemical reactions under certain conditions in biological fluids or tissues. This technology has been used extensively to identify biomarkers in various cancers, nervous system diseases, cardiovascular diseases, pituitary diseases, and other diseases. The identification of biomarkers can be clinically useful for a more accurate diagnosis, prognosis, and treatment choice as well as disease monitoring. Among mass spectrometry (MS) methods, liquid chromatography- mass spectrometry (LC-MS) has been recognized as a robust metabolomics tool and has been widely applied in metabolite identification and quantification due to its high sensitivity, peak resolution, and reproducibility.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Third Military Medical University

OTHER

Sponsor Role: lead

Responsible Party

Zhiming Zhu

Director of the department of Hypertension & Endocrinology, Daping Hospital

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

China Chongqing The third hospital affiliated to the Third Millitary Medical University

Chongqing, Chongqing Municipality, China

Countries

China

Other Identifiers

MP of PA

Identifier Type: -

Identifier Source: org_study_id