Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
COMPLETED
Total Enrollment
1380 participants
Study Classification
OBSERVATIONAL
Study Start Date
2007-09-01
Study Completion Date
2020-07-01
Brief Summary
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Recent studies on catecholamine physiology have shown a direct correlation with arterial hypertension, overcoming the exclusive role in the diagnosis and follow-up of chromaffin tumors.
Nevertheless, in literature, few studies explore and reveal the utility of testing metanephrines for the evaluation of sympathetic activity and its associated cardiometabolic complications in patients with essential hypertension.
Nevertheless, in literature, few studies explore and reveal the utility of testing metanephrines for the evaluation of sympathetic activity and its associated cardiometabolic complications in patients with essential hypertension.
Detailed Description
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Catecholamines (noradrenaline, adrenaline and dopamine) are adaptive and maladaptive stress hormones.
In the classic "fight or flight" mechanism, they activate behavioral and physiological processes that facilitate the overcoming of stress; for instance, challenged by a physical stressor, an organism responds to the threat either fighting and prevailing or accepting defeat and fleeing in avoidance.
In the pathological context, an excessive catecholamine secretion is typical of the chromaffin tissue tumors, determining a clinical picture characterized by blood pressure elevation, tachycardia, anxiety, pallor, sweating and headache.
COMT enzyme catalyzes the O-methylation of the 3-hydroxyl group of catecholamines. The O-methylated derivatives of noradrenaline, adrenaline and dopamine are normetanephrine, metanephrine and 3-methoxytyramine, respectively. The term "metanephrines" is generally used to collectively refer to the first two compounds.
Compared to catecholamines, metanephrines are characterized by longer half-life and more stable levels over time. Their superior accuracy for the diagnosis and follow-up of pheochromocytoma and paraganglioma (PPGL) has been widely proved.
Excluding patients with PPGL, however, metanephrines can be more broadly considered as reliable markers of the whole sympathetic system activity; therefore, their levels may be hypothesized to be associated to a higher rate of concurrent cardiometabolic complications and, if so, could be useful for the stratification of cardiovascular risk.
In the classic "fight or flight" mechanism, they activate behavioral and physiological processes that facilitate the overcoming of stress; for instance, challenged by a physical stressor, an organism responds to the threat either fighting and prevailing or accepting defeat and fleeing in avoidance.
In the pathological context, an excessive catecholamine secretion is typical of the chromaffin tissue tumors, determining a clinical picture characterized by blood pressure elevation, tachycardia, anxiety, pallor, sweating and headache.
COMT enzyme catalyzes the O-methylation of the 3-hydroxyl group of catecholamines. The O-methylated derivatives of noradrenaline, adrenaline and dopamine are normetanephrine, metanephrine and 3-methoxytyramine, respectively. The term "metanephrines" is generally used to collectively refer to the first two compounds.
Compared to catecholamines, metanephrines are characterized by longer half-life and more stable levels over time. Their superior accuracy for the diagnosis and follow-up of pheochromocytoma and paraganglioma (PPGL) has been widely proved.
Excluding patients with PPGL, however, metanephrines can be more broadly considered as reliable markers of the whole sympathetic system activity; therefore, their levels may be hypothesized to be associated to a higher rate of concurrent cardiometabolic complications and, if so, could be useful for the stratification of cardiovascular risk.
Conditions
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Catecholamine; Overproduction
Catecholamine; Secretion
Metabolic Syndrome
Hypertensive Heart Disease
Hypertensive Kidney Disease
Diabetes Mellitus, Type 2
Hypertension,Essential
Keywords
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Normetanephrine
Metanephrine
Sympathetic Nervous System
Cardiovascular System
Cardiometabolic Complications
Catecholamine; Overproduction
Catecholamine; Secretion
Metabolic Syndrome
Hypertensive Heart Disease
Hypertensive Kidney Disease
Diabetes Mellitus, Type 2
Hypertension,Essential
Study Design
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Observational Model Type
CASE_ONLY
Study Time Perspective
CROSS_SECTIONAL
Eligibility Criteria
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Inclusion Criteria
* Measurement of 24h urinary metanephrines at the laboratory of "City of Health and Science" hospital in Turin between 2007 and 2015
* Availability of contextual clinical patient data as collected in prospective registries of Piedmont region
* Availability of contextual clinical patient data as collected in prospective registries of Piedmont region
Exclusion Criteria
* Diagnosis of pheochromocytoma or paraganglioma (at the time of urinary metanephrines collection or within the following 5 years)
* Diagnosis of other forms of secondary hypertension
* Previous cardiovascular or cerebrovascular event
* Chronic heart failure
* eGFR \< 50 ml/min (according to CKD-EPI)
* Liver cirrhosis
* Acute conditions and/or hospitalization in ICU (at the time of urinary metanephrines collection)
* Assumption of acetaminophen during the day before the 24-hour urine collection
* Therapy with labetalol
* Therapy with sotalol
* Therapy with alpha-methyldopa
* Therapy with MAO inhibitors
* Therapy with tricyclic antidepressants
* Therapy with buspirone
* Therapy with phenoxybenzamine
* Therapy with sulfasalazine
* Therapy with L-Dopa
* Therapy with sympathomimetic drugs or other vasopressors
* Alcohol abuse
* Cocaine abuse
* Diagnosis of other forms of secondary hypertension
* Previous cardiovascular or cerebrovascular event
* Chronic heart failure
* eGFR \< 50 ml/min (according to CKD-EPI)
* Liver cirrhosis
* Acute conditions and/or hospitalization in ICU (at the time of urinary metanephrines collection)
* Assumption of acetaminophen during the day before the 24-hour urine collection
* Therapy with labetalol
* Therapy with sotalol
* Therapy with alpha-methyldopa
* Therapy with MAO inhibitors
* Therapy with tricyclic antidepressants
* Therapy with buspirone
* Therapy with phenoxybenzamine
* Therapy with sulfasalazine
* Therapy with L-Dopa
* Therapy with sympathomimetic drugs or other vasopressors
* Alcohol abuse
* Cocaine abuse
Minimum Eligible Age
18 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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University of Turin, Italy
OTHER
Sponsor Role
lead
Responsible Party
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Mauro Maccario
Medical Doctor, Professor
Responsibility Role
PRINCIPAL_INVESTIGATOR
Principal Investigators
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Mauro Maccario, MD
Role: PRINCIPAL_INVESTIGATOR
Endocrinology, Diabetology and Metabolism; University of Turin
Ezio Ghigo, MD
Role: STUDY_CHAIR
Endocrinology, Diabetology and Metabolism; University of Turin
Locations
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Division of Endocrinology, Diabetology and Metabolism; University of Turin
Turin, Piedmont, Italy
Site Status
Countries
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Italy
References
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Ton QV, Hammes SR. Recent insights on circulating catecholamines in hypertension. Curr Hypertens Rep. 2014 Dec;16(12):498. doi: 10.1007/s11906-014-0498-9.
Reference Type
BACKGROUND
Esler M. The sympathetic nervous system in hypertension: back to the future? Curr Hypertens Rep. 2015 Feb;17(2):11. doi: 10.1007/s11906-014-0519-8.
Reference Type
BACKGROUND
Coulson JM. The relationship between blood pressure variability and catecholamine metabolites: a pilot study. J Hum Hypertens. 2015 Jan;29(1):50-2. doi: 10.1038/jhh.2014.23. Epub 2014 Apr 3.
Reference Type
BACKGROUND
Lenders JW, Duh QY, Eisenhofer G, Gimenez-Roqueplo AP, Grebe SK, Murad MH, Naruse M, Pacak K, Young WF Jr; Endocrine Society. Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014 Jun;99(6):1915-42. doi: 10.1210/jc.2014-1498.
Reference Type
BACKGROUND
Okuyama Y, Sakata Y. [Device treatment approaches targeting the sympathetic nervous system in patients with resistant hypertension]. Nihon Rinsho. 2015 Nov;73(11):1857-63. Japanese.
Reference Type
BACKGROUND
Grassi G, Mark A, Esler M. The sympathetic nervous system alterations in human hypertension. Circ Res. 2015 Mar 13;116(6):976-90. doi: 10.1161/CIRCRESAHA.116.303604.
Reference Type
BACKGROUND
Rothwell PM, Howard SC, Dolan E, O'Brien E, Dobson JE, Dahlof B, Sever PS, Poulter NR. Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension. Lancet. 2010 Mar 13;375(9718):895-905. doi: 10.1016/S0140-6736(10)60308-X.
Reference Type
BACKGROUND
Esler M, Lambert G, Jennings G. Increased regional sympathetic nervous activity in human hypertension: causes and consequences. J Hypertens Suppl. 1990 Dec;8(7):S53-7.
Reference Type
BACKGROUND
Eisenhofer G, Kopin IJ, Goldstein DS. Catecholamine metabolism: a contemporary view with implications for physiology and medicine. Pharmacol Rev. 2004 Sep;56(3):331-49. doi: 10.1124/pr.56.3.1.
Reference Type
BACKGROUND
Tank AW, Lee Wong D. Peripheral and central effects of circulating catecholamines. Compr Physiol. 2015 Jan;5(1):1-15. doi: 10.1002/cphy.c140007.
Reference Type
BACKGROUND
Goldstein DS, Eisenhofer G, Kopin IJ. Sources and significance of plasma levels of catechols and their metabolites in humans. J Pharmacol Exp Ther. 2003 Jun;305(3):800-11. doi: 10.1124/jpet.103.049270. Epub 2003 Mar 20.
Reference Type
BACKGROUND
Eisenhofer G, Friberg P, Pacak K, Goldstein DS, Murphy DL, Tsigos C, Quyyumi AA, Brunner HG, Lenders JW. Plasma metadrenalines: do they provide useful information about sympatho-adrenal function and catecholamine metabolism? Clin Sci (Lond). 1995 May;88(5):533-42. doi: 10.1042/cs0880533.
Reference Type
BACKGROUND
Masuo K, Kawaguchi H, Mikami H, Ogihara T, Tuck ML. Serum uric acid and plasma norepinephrine concentrations predict subsequent weight gain and blood pressure elevation. Hypertension. 2003 Oct;42(4):474-80. doi: 10.1161/01.HYP.0000091371.53502.D3. Epub 2003 Sep 2.
Reference Type
BACKGROUND
Dudenbostel T, Acelajado MC, Pisoni R, Li P, Oparil S, Calhoun DA. Refractory Hypertension: Evidence of Heightened Sympathetic Activity as a Cause of Antihypertensive Treatment Failure. Hypertension. 2015 Jul;66(1):126-33. doi: 10.1161/HYPERTENSIONAHA.115.05449. Epub 2015 May 18.
Reference Type
BACKGROUND
Flaa A, Aksnes TA, Kjeldsen SE, Eide I, Rostrup M. Increased sympathetic reactivity may predict insulin resistance: an 18-year follow-up study. Metabolism. 2008 Oct;57(10):1422-7. doi: 10.1016/j.metabol.2008.05.012.
Reference Type
BACKGROUND
Masuo K, Mikami H, Ogihara T, Tuck ML. Sympathetic nerve hyperactivity precedes hyperinsulinemia and blood pressure elevation in a young, nonobese Japanese population. Am J Hypertens. 1997 Jan;10(1):77-83. doi: 10.1016/s0895-7061(96)00303-2.
Reference Type
BACKGROUND
Quarti Trevano F, Dell'Oro R, Biffi A, Seravalle G, Corrao G, Mancia G, Grassi G. Sympathetic overdrive in the metabolic syndrome: meta-analysis of published studies. J Hypertens. 2020 Apr;38(4):565-572. doi: 10.1097/HJH.0000000000002288.
Reference Type
BACKGROUND
Mancia G, Bousquet P, Elghozi JL, Esler M, Grassi G, Julius S, Reid J, Van Zwieten PA. The sympathetic nervous system and the metabolic syndrome. J Hypertens. 2007 May;25(5):909-20. doi: 10.1097/HJH.0b013e328048d004.
Reference Type
BACKGROUND
Straznicky NE, Grima MT, Sari CI, Karapanagiotidis S, Wong C, Eikelis N, Richards KL, Lee G, Nestel PJ, Dixon JB, Lambert GW, Schlaich MP, Lambert EA. The relation of glucose metabolism to left ventricular mass and function and sympathetic nervous system activity in obese subjects with metabolic syndrome. J Clin Endocrinol Metab. 2013 Feb;98(2):E227-37. doi: 10.1210/jc.2012-3277. Epub 2012 Dec 27.
Reference Type
BACKGROUND
Schlaich MP, Kaye DM, Lambert E, Sommerville M, Socratous F, Esler MD. Relation between cardiac sympathetic activity and hypertensive left ventricular hypertrophy. Circulation. 2003 Aug 5;108(5):560-5. doi: 10.1161/01.CIR.0000081775.72651.B6. Epub 2003 Jul 7.
Reference Type
BACKGROUND
Wang W, Mu L, Su T, Ye L, Jiang Y, Jiang L, Zhou W. Plasma Metanephrines Are Associated With Glucose Metabolism in Patients With Essential Hypertension. Medicine (Baltimore). 2015 Sep;94(37):e1496. doi: 10.1097/MD.0000000000001496.
Reference Type
BACKGROUND
Brown MJ, Causon RC, Barnes VF, Brennan P, Barnes G, Greenberg G. Urinary catecholamines in essential hypertension: results of 24-hour urine catecholamine analyses from patients in the Medical Research Council trial for mild hypertension and from matched controls. Q J Med. 1985 Oct;57(222):637-51.
Reference Type
BACKGROUND
Zhou Y, Yuan J, Wang Y, Qiao S. Plasma metanephrins are associated with myocardial hypertrophy and cardiac diastolic function in patients with essential hypertension. Clin Invest Med. 2020 Apr 5;43(1):E22-E29. doi: 10.25011/cim.v43i1.33581.
Reference Type
BACKGROUND
Other Identifiers
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SympAct 1
Identifier Type: -
Identifier Source: org_study_id