- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT06049641
Hypertension hos gymnasieelever (HYGEF)
Hypertension hos gymnasieelever: genetiske og miljømæssige faktorer
Studieoversigt
Status
Betingelser
Detaljeret beskrivelse
Pædiatrisk hypertension er forbundet med kardiovaskulær organskade, som igen kan føre til kardiovaskulær sygdom (CVD) og akutte hændelser i voksenalderen.1 I løbet af de sidste par årtier er forekomsten af hypertension gradvist steget hos børn og unge, hvilket har skabt et betydeligt folkesundhedsproblem og en betydelig mængde forskning. BP-værdier blandt unge har en tendens til at være mindre heterogene end hos voksne, og virkningen af genetiske faktorer, selvom de er små, kan være udtryk for patogene mekanismer, der har været til stede siden fødslen.
Med denne undersøgelse, kaldet HYGEF (Hypertension in high school students: Genetic and Environmental Factors), ønskede forfatterne at: 1. bestemme forekomsten af fedme og hypertension (HT) i en kohorte af unge, 2. udføre genetiske analyser for at bestemme en sammenhæng mellem specifikke polymorfier og/eller mutationer af gener involveret i udviklingen af HT hos voksne som Adducingenerne og Endogen Ouabain (EO) og HT og 3. undersøge, om urin Na+/K+ udskillelse og urinmarkører for inflammation og oxidativ stress er forbundet med HT og kardiovaskulær risiko hos deltagere med de udvalgte genotyper.
Unge vil blive tilmeldt undersøgelsen på gymnasier i det nordlige (Milano), centrum (Livorno) og syd (Grottaglie) af Italien, for at opnå en prøve, der kunne være repræsentativ for de italienske unge. Under besøget på gymnasiet indhenter efterforskerne spørgeskemaer for at have nogle oplysninger om spisevaner, livsstil og familiehistorie, to (eller tre i de var meget uenige) blodtryksmålinger, vægt og højde af eleverne, en urinprøve og en prøve af spyt for at ekstrahere DNA.
Genotyping: På baggrund af vores tidligere genetiske undersøgelser udført i voksne patienter med hypertension og kardiovaskulære og nyrerelaterede sygdomme, er 15 SNP'er lokaliseret i 13 kandidatgener blevet udvalgt: rs1045642 i ABCB1, rs4343 i ACE (angiotensin converting enzyme), rs4961 ADD1 (alfa-adducin), rs4984 i ADD2 (beta-adducin), rs3731566 i ADD3 (gamma-adducin), rs11638442 i CYP11A1 (cytokrom P450 familie 11 underfamilie A medlem 1), rs1827 in 9, rs1827 9, rs1827 9 236780, rs6203 og rs10923835 i HSD3B1 genetisk region, rs9536314 i KL, rs2254524 i LSS, rs4149601 i neurale precursorcelle udtrykt, udviklingsmæssigt nedreguleret 4-lignende, NEDD4L (E3 ubiquitin-protein-protein 4MPs, PRK1 ligaprotein, PRK1 ligaprotein-protein 9MP, 4149601) -afhængig, type I), rs4238595 i UMOD (uromodulin).
Analyse af urin: Na+, K+, albumin og kreatinin blev målt på en første fastende morgenurinprøve. Kawasaki-formlen blev brugt til at estimere 24-timers urinudskillelse af natrium (24 timer UNa) udtrykt som mEq/24 timer. I en undergruppe vil en urinpletprøve for hver elev straks blive frosset til proteinanalyse. Efterforskere planlægger samtidig at måle IL1β, IL6, IL10, IL12p70, TNF-α, MCP1 (monocyt kemoattraktant protein), PTX3 (pentraxin-3) ved ELISA-test ved hjælp af LXSAHM Human Magnetic Luminex Screening Assay. Opløselig α-Klotho, 8-Oxo-2'-deoxyguanosin vil blive målt ved Elisa kit-assay. Nitrogenoxid (NO) blev målt med det kolorimetriske nitrogenoxid-assay-kit. Advanced Oxidation Protein Products vil blive målt ved hjælp af det kolorimetriske OxiSelect Advanced Oxidation Protein Products Assay Kit.
Undersøgelsestype
Tilmelding (Faktiske)
Kontakter og lokationer
Studiesteder
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Milan, Italien, 20132
- IRCCS Ospedale San Raffaele
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
- Barn
- Voksen
Tager imod sunde frivillige
Prøveudtagningsmetode
Studiebefolkning
Beskrivelse
Inklusionskriterier:
- Alder mellem 13 og 19 år
- kaukasisk
Ekskluderingskriterier:
- Alder mere end 19 år gammel
- Ikke kaukasisk
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
Kohorter og interventioner
Gruppe / kohorte |
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13 til 15 år
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16 til 19 årig
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Tidsramme |
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Formålet med undersøgelsen var at etablere en sammenhæng mellem specifikke polymorfier af Adduciner og EO-relaterede gener med udvalgte fænotyper (hypertension, Na+ og K+ indtag).
Tidsramme: 2 år
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2 år
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Samarbejdspartnere og efterforskere
Sponsor
Publikationer og nyttige links
Generelle publikationer
- National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics. 2004 Aug;114(2 Suppl 4th Report):555-76. No abstract available.
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- Appel LJ, Brands MW, Daniels SR, Karanja N, Elmer PJ, Sacks FM; American Heart Association. Dietary approaches to prevent and treat hypertension: a scientific statement from the American Heart Association. Hypertension. 2006 Feb;47(2):296-308. doi: 10.1161/01.HYP.0000202568.01167.B6.
- Staessen JA, Wang JG, Brand E, Barlassina C, Birkenhager WH, Herrmann SM, Fagard R, Tizzoni L, Bianchi G. Effects of three candidate genes on prevalence and incidence of hypertension in a Caucasian population. J Hypertens. 2001 Aug;19(8):1349-58. doi: 10.1097/00004872-200108000-00002. Erratum In: J Hypertens 2001 Oct;19(10):1921.
- Intersalt: an international study of electrolyte excretion and blood pressure. Results for 24 hour urinary sodium and potassium excretion. Intersalt Cooperative Research Group. BMJ. 1988 Jul 30;297(6644):319-28. doi: 10.1136/bmj.297.6644.319.
- Polonia J, Lobo MF, Martins L, Pinto F, Nazare J. Estimation of populational 24-h urinary sodium and potassium excretion from spot urine samples: evaluation of four formulas in a large national representative population. J Hypertens. 2017 Mar;35(3):477-486. doi: 10.1097/HJH.0000000000001180.
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- Liu M, Li Y, Citterio L, Huang QF, Zeng WF, Sheng CS, Wei FF, Dong Q, Li GL, Kang YY, Zhang L, Xu TY, Li JJ, Song J, Manunta P, Wang JG. A functional common polymorphism of the ABCB1 gene is associated with chronic kidney disease and hypertension in Chinese. Am J Hypertens. 2013 Dec;26(12):1428-36. doi: 10.1093/ajh/hpt126. Epub 2013 Aug 7.
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- Efendiev R, Krmar RT, Ogimoto G, Zwiller J, Tripodi G, Katz AI, Bianchi G, Pedemonte CH, Bertorello AM. Hypertension-linked mutation in the adducin alpha-subunit leads to higher AP2-mu2 phosphorylation and impaired Na+,K+-ATPase trafficking in response to GPCR signals and intracellular sodium. Circ Res. 2004 Nov 26;95(11):1100-8. doi: 10.1161/01.RES.0000149570.20845.89. Epub 2004 Nov 4.
- Manunta P, Maillard M, Tantardini C, Simonini M, Lanzani C, Citterio L, Stella P, Casamassima N, Burnier M, Hamlyn JM, Bianchi G. Relationships among endogenous ouabain, alpha-adducin polymorphisms and renal sodium handling in primary hypertension. J Hypertens. 2008 May;26(5):914-20. doi: 10.1097/HJH.0b013e3282f5315f.
- Ferrari P. Rostafuroxin: an ouabain-inhibitor counteracting specific forms of hypertension. Biochim Biophys Acta. 2010 Dec;1802(12):1254-8. doi: 10.1016/j.bbadis.2010.01.009. Epub 2010 Jan 18.
- Blaustein MP, Chen L, Hamlyn JM, Leenen FH, Lingrel JB, Wier WG, Zhang J. Pivotal role of alpha2 Na+ pumps and their high affinity ouabain binding site in cardiovascular health and disease. J Physiol. 2016 Nov 1;594(21):6079-6103. doi: 10.1113/JP272419. Epub 2016 Jul 31.
- Manunta P, Iacoviello M, Forleo C, Messaggio E, Hamlyn JM, Lucarelli K, Guida P, Romito R, De Tommasi E, Bianchi G, Rizzon P, Pitzalis MV. High circulating levels of endogenous ouabain in the offspring of hypertensive and normotensive individuals. J Hypertens. 2005 Sep;23(9):1677-81. doi: 10.1097/01.hjh.0000177049.38417.67.
- Nzietchueng R, El Shamieh S, Benachour H, Labat C, Herbeth B, Ndiaye NC, Masson C, Visvikis-Siest S, Benetos A. Klotho KL-VS genotype is involved in blood pressure regulation. Clin Chim Acta. 2011 Sep 18;412(19-20):1773-7. doi: 10.1016/j.cca.2011.05.032. Epub 2011 Jun 1.
- Zhou X, Chen K, Lei H, Sun Z. Klotho gene deficiency causes salt-sensitive hypertension via monocyte chemotactic protein-1/CC chemokine receptor 2-mediated inflammation. J Am Soc Nephrol. 2015 Jan;26(1):121-32. doi: 10.1681/ASN.2013101033. Epub 2014 Jun 5.
- Manunta P, Lavery G, Lanzani C, Braund PS, Simonini M, Bodycote C, Zagato L, Delli Carpini S, Tantardini C, Brioni E, Bianchi G, Samani NJ. Physiological interaction between alpha-adducin and WNK1-NEDD4L pathways on sodium-related blood pressure regulation. Hypertension. 2008 Aug;52(2):366-72. doi: 10.1161/HYPERTENSIONAHA.108.113977. Epub 2008 Jun 30.
- Citterio L, Simonini M, Zagato L, Salvi E, Delli Carpini S, Lanzani C, Messaggio E, Casamassima N, Frau F, D'Avila F, Cusi D, Barlassina C, Manunta P. Genes involved in vasoconstriction and vasodilation system affect salt-sensitive hypertension. PLoS One. 2011 May 9;6(5):e19620. doi: 10.1371/journal.pone.0019620.
- Trudu M, Janas S, Lanzani C, Debaix H, Schaeffer C, Ikehata M, Citterio L, Demaretz S, Trevisani F, Ristagno G, Glaudemans B, Laghmani K, Dell'Antonio G; SKIPOGH team; Loffing J, Rastaldi MP, Manunta P, Devuyst O, Rampoldi L. Common noncoding UMOD gene variants induce salt-sensitive hypertension and kidney damage by increasing uromodulin expression. Nat Med. 2013 Dec;19(12):1655-60. doi: 10.1038/nm.3384. Epub 2013 Nov 3.
- Kuznetsova T, Staessen JA, Thijs L, Kunath C, Olszanecka A, Ryabikov A, Tikhonoff V, Stolarz K, Bianchi G, Casiglia E, Fagard R, Brand-Herrmann SM, Kawecka-Jaszcz K, Malyutina S, Nikitin Y, Brand E; European Project On Genes in Hypertension (EPOGH) Investigators. Left ventricular mass in relation to genetic variation in angiotensin II receptors, renin system genes, and sodium excretion. Circulation. 2004 Oct 26;110(17):2644-50. doi: 10.1161/01.CIR.0000145541.63406.BA. Epub 2004 Oct 18.
- Munshi A, Sharma V, Kaul S, Rajeshwar K, Babu MS, Shafi G, Anila AN, Balakrishna N, Alladi S, Jyothy A. Association of the -344C/T aldosterone synthase (CYP11B2) gene variant with hypertension and stroke. J Neurol Sci. 2010 Sep 15;296(1-2):34-8. doi: 10.1016/j.jns.2010.06.013. Epub 2010 Jul 3. Erratum In: J Neurol Sci. 2012 Oct 15;321(1-2):122.
- Tanase DM, Gosav EM, Radu S, Ouatu A, Rezus C, Ciocoiu M, Costea CF, Floria M. Arterial Hypertension and Interleukins: Potential Therapeutic Target or Future Diagnostic Marker? Int J Hypertens. 2019 May 2;2019:3159283. doi: 10.1155/2019/3159283. eCollection 2019.
- Li Y, Thijs L, Kuznetsova T, Zagato L, Struijker-Boudier H, Bianchi G, Staessen JA. Cardiovascular risk in relation to alpha-adducin Gly460Trp polymorphism and systolic pressure: a prospective population study. Hypertension. 2005 Sep;46(3):527-32. doi: 10.1161/01.HYP.0000174988.81829.72. Epub 2005 Jul 25.
- Manunta P, Ferrandi M, Cusi D, Ferrari P, Staessen J, Bianchi G. Personalized Therapy of Hypertension: the Past and the Future. Curr Hypertens Rep. 2016 Mar;18(3):24. doi: 10.1007/s11906-016-0632-y.
- Seidlerova J, Staessen JA, Bochud M, Nawrot T, Casamassima N, Citterio L, Kuznetsova T, Jin Y, Manunta P, Richart T, Struijker-Boudier HA, Fagard R, Filipovsky J, Bianchi G. Arterial properties in relation to genetic variations in the adducin subunits in a white population. Am J Hypertens. 2009 Jan;22(1):21-6. doi: 10.1038/ajh.2008.261. Epub 2008 Sep 11.
- Iatrino R, Lanzani C, Bignami E, Casamassima N, Citterio L, Meroni R, Zagato L, Zangrillo A, Alfieri O, Fontana S, Macrina L, Delli Carpini S, Messaggio E, Brioni E, Dell'Antonio G, Manunta P, Hamlyn JM, Simonini M. Lanosterol Synthase Genetic Variants, Endogenous Ouabain, and Both Acute and Chronic Kidney Injury. Am J Kidney Dis. 2019 Apr;73(4):504-512. doi: 10.1053/j.ajkd.2018.10.012. Epub 2019 Jan 16.
- Citterio L, Ferrandi M, Delli Carpini S, Simonini M, Kuznetsova T, Molinari I, Dell' Antonio G, Lanzani C, Merlino L, Brioni E, Staessen JA, Bianchi G, Manunta P. cGMP-dependent protein kinase 1 polymorphisms underlie renal sodium handling impairment. Hypertension. 2013 Dec;62(6):1027-33. doi: 10.1161/HYPERTENSIONAHA.113.01628. Epub 2013 Sep 23.
- Kawasaki T, Itoh K, Uezono K, Sasaki H. A simple method for estimating 24 h urinary sodium and potassium excretion from second morning voiding urine specimen in adults. Clin Exp Pharmacol Physiol. 1993 Jan;20(1):7-14. doi: 10.1111/j.1440-1681.1993.tb01496.x. Erratum In: Clin Exp Pharmacol Physiol 1993 Mar;20(3):199.
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- Welsh CE, Welsh P, Jhund P, Delles C, Celis-Morales C, Lewsey JD, Gray S, Lyall D, Iliodromiti S, Gill JMR, Sattar N, Mark PB. Urinary Sodium Excretion, Blood Pressure, and Risk of Future Cardiovascular Disease and Mortality in Subjects Without Prior Cardiovascular Disease. Hypertension. 2019 Jun;73(6):1202-1209. doi: 10.1161/HYPERTENSIONAHA.119.12726.
- Andrukhova O, Slavic S, Smorodchenko A, Zeitz U, Shalhoub V, Lanske B, Pohl EE, Erben RG. FGF23 regulates renal sodium handling and blood pressure. EMBO Mol Med. 2014 Jun;6(6):744-59. doi: 10.1002/emmm.201303716. Epub 2014 Apr 6.
- Cusi D, Barlassina C, Azzani T, Casari G, Citterio L, Devoto M, Glorioso N, Lanzani C, Manunta P, Righetti M, Rivera R, Stella P, Troffa C, Zagato L, Bianchi G. Polymorphisms of alpha-adducin and salt sensitivity in patients with essential hypertension. Lancet. 1997 May 10;349(9062):1353-7. doi: 10.1016/S0140-6736(97)01029-5. Erratum In: Lancet 1997 Aug 16;350(9076):524.
- Taylor WR. Hypertensive vascular disease and inflammation: mechanical and humoral mechanisms. Curr Hypertens Rep. 1999 Feb-Mar;1(1):96-101. doi: 10.1007/s11906-999-0079-5.
- Libby P. Interleukin-1 Beta as a Target for Atherosclerosis Therapy: Biological Basis of CANTOS and Beyond. J Am Coll Cardiol. 2017 Oct 31;70(18):2278-2289. doi: 10.1016/j.jacc.2017.09.028.
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- Elijovich F, Weinberger MH, Anderson CA, Appel LJ, Bursztyn M, Cook NR, Dart RA, Newton-Cheh CH, Sacks FM, Laffer CL; American Heart Association Professional and Public Education Committee of the Council on Hypertension; Council on Functional Genomics and Translational Biology; and Stroke Council. Salt Sensitivity of Blood Pressure: A Scientific Statement From the American Heart Association. Hypertension. 2016 Sep;68(3):e7-e46. doi: 10.1161/HYP.0000000000000047. Epub 2016 Jul 21. No abstract available. Erratum In: Hypertension. 2016 Oct;68(4):e62.
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- Tentori S, Messaggio E, Brioni E, Casamassima N, Simonini M, Zagato L, Hamlyn JM, Manunta P, Lanzani C. Endogenous ouabain and aldosterone are coelevated in the circulation of patients with essential hypertension. J Hypertens. 2016 Oct;34(10):2074-80. doi: 10.1097/HJH.0000000000001042.
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Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- HYGEF STUDY
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
Studerer et amerikansk FDA-reguleret lægemiddelprodukt
Studerer et amerikansk FDA-reguleret enhedsprodukt
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