- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT01745471
Fedtvæv og polycystisk ovariesyndrom (PCOS) (EIFFEL) (EIFFEL)
Angiogenese af fedtvæv i polycystisk ovariesyndrom (PCOS)
Studieoversigt
Status
Betingelser
Detaljeret beskrivelse
Undersøgelsestype
Tilmelding (Anslået)
Kontakter og lokationer
Studiesteder
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Florida
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Orlando, Florida, Forenede Stater, 32804
- Translational Research Institute for Metabolism and Diabetes
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Prøveudtagningsmetode
Studiebefolkning
Beskrivelse
Inklusionskriterier:
- Kvinde
- Alder > 20 og < 40
- Vægtstabil (ændring på mindre end 3 kg inden for de sidste 8 uger)
- BMI < 40 kg/m2 eller > 27 kg/m2
Supplerende inklusionskriterier for PCOS-kvinder:
- NIH kriterier - bekræftet af forsøgspersoners lægejournaler.
Ekskluderingskriterier:
- Han
- Kvinder, der er gravide eller ammer (ammer)
- Postmenopausale kvinder
- Kvinder med hysterektomi
- Diagnosticeret med diabetes eller har et fasteblodsukker > 126 mg/dL.
- Ubehandlet eller symptomatisk skjoldbruskkirtelsygdom.
- Nedsat nyre- eller leverfunktion, som det fremgår af dit blodarbejde
- Hypertension/forhøjet blodtryk eller tager blodtryksmedicin
- Brug af orale præventionsmidler eller hormonbehandling.
- Anamnese med stof- eller alkoholmisbrug (> 3 drinks om dagen) inden for de sidste 5 år, eller psykiatrisk sygdom, der forbyder overholdelse af undersøgelsesprotokol.
- Anamnese med kræft inden for de sidste 5 år.
- Historie om organtransplantation.
- Anamnese med HIV, aktiv hepatitis B eller C eller tuberkulose.
- Anamnese med hjerteanfald/myokardieinfarkt.
- Tilstedeværelse af klinisk signifikante abnormiteter på EKG.
- Nuværende rygere (ryger inden for de seneste 3 måneder)
- Brug af medicin, der vides at påvirke glukose-, fedt- og/eller energimetabolismen inden for de sidste 3 måneder (f.eks. væksthormonbehandling, glukokortikoider [steroider] osv.). Metformin til kvinder med PCOS er tilladt.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Observationsmodeller: Case-Control
- Tidsperspektiver: Fremadrettet
Kohorter og interventioner
Gruppe / kohorte |
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PCOS gruppe
12 kvinder med polycystisk ovariesyndrom (PCOS) som defineret af NIH-kriterier
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Pære former
12 med et Android-mønster som defineret ved en talje-til-hofte større end 0,85
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Æble former
12 vil have et gynoidmønster som defineret ved et talje-til-hofte-forhold på mindre end 0,78
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Forskel i angiogenesekapacitet i abdominalt og glutealt fedtvæv
Tidsramme: Dag 7
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Hvert fedtvævsdepots angiogenesekapacitet bestemmes ved en in vitro angiogenesetest.
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Dag 7
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Tilstedeværelse af biomarkører i abdominalt og glutealt fedtvæv hos overvægtige og PCOS-kvinder
Tidsramme: Dag 7
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Måling vil blive opnået med Fluorescens-aktiveret cellesortering (FACS). Identificer forskellige og lignende biomarkører hos overvægtige og PCOS kvinder, fra abdominale og gluteale fedtvævsprøver. Totalt RNA, mikro-RNA og DNA vil blive ekstraheret fra hver type celler ved hjælp af FACS-cellesorteringsanalyse. |
Dag 7
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Forskel i iltindhold i abdominalt og glutealt fedtvæv
Tidsramme: Dag 6
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Oxygenindholdet i fedtvævet vil blive målt ved hjælp af Licox CMP-mikroprocessoren.
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Dag 6
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Andre resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Satserne for kulhydratoxidation
Tidsramme: Dag -7
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Resting Metabolic Rate (RMR) vil måle hvilemetabolic rate/respiratorisk kvotient (RMR/RQ) og substratudnyttelse. Energiforbrug og respirationskvotient standardiseret for temperatur, tryk og fugt vil blive beregnet med et minuts intervaller over 30 minutter. |
Dag -7
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Hastighederne for lipidoxidation
Tidsramme: Dag -7
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Resting Metabolic Rate (RMR) vil måle hvilemetabolic rate/respiratorisk kvotient (RMR/RQ) og substratudnyttelse. Energiforbrug og respirationskvotient standardiseret for temperatur, tryk og fugt vil blive beregnet med et minuts intervaller over 30 minutter. |
Dag -7
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Samarbejdspartnere og efterforskere
Samarbejdspartnere
Efterforskere
- Ledende efterforsker: Adeline Divoux, PhD, Translational Research Institute for Metabolism and Diabetes
- Ledende efterforsker: Steven R Smith, MD, Translational Research Institute for Metabolism and Diabetes
Publikationer og nyttige links
Generelle publikationer
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- Tran TT, Yamamoto Y, Gesta S, Kahn CR. Beneficial effects of subcutaneous fat transplantation on metabolism. Cell Metab. 2008 May;7(5):410-20. doi: 10.1016/j.cmet.2008.04.004.
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- Cinti S, Mitchell G, Barbatelli G, Murano I, Ceresi E, Faloia E, Wang S, Fortier M, Greenberg AS, Obin MS. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res. 2005 Nov;46(11):2347-55. doi: 10.1194/jlr.M500294-JLR200. Epub 2005 Sep 8.
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- Rogers NH, Perfield JW 2nd, Strissel KJ, Obin MS, Greenberg AS. Reduced energy expenditure and increased inflammation are early events in the development of ovariectomy-induced obesity. Endocrinology. 2009 May;150(5):2161-8. doi: 10.1210/en.2008-1405. Epub 2009 Jan 29.
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- Hirosumi J, Tuncman G, Chang L, Gorgun CZ, Uysal KT, Maeda K, Karin M, Hotamisligil GS. A central role for JNK in obesity and insulin resistance. Nature. 2002 Nov 21;420(6913):333-6. doi: 10.1038/nature01137.
- Hotamisligil GS, Murray DL, Choy LN, Spiegelman BM. Tumor necrosis factor alpha inhibits signaling from the insulin receptor. Proc Natl Acad Sci U S A. 1994 May 24;91(11):4854-8. doi: 10.1073/pnas.91.11.4854.
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- Macotela Y, Boucher J, Tran TT, Kahn CR. Sex and depot differences in adipocyte insulin sensitivity and glucose metabolism. Diabetes. 2009 Apr;58(4):803-12. doi: 10.2337/db08-1054. Epub 2009 Jan 9.
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- D'Eon TM, Souza SC, Aronovitz M, Obin MS, Fried SK, Greenberg AS. Estrogen regulation of adiposity and fuel partitioning. Evidence of genomic and non-genomic regulation of lipogenic and oxidative pathways. J Biol Chem. 2005 Oct 28;280(43):35983-91. doi: 10.1074/jbc.M507339200. Epub 2005 Aug 17.
- Riant E, Waget A, Cogo H, Arnal JF, Burcelin R, Gourdy P. Estrogens protect against high-fat diet-induced insulin resistance and glucose intolerance in mice. Endocrinology. 2009 May;150(5):2109-17. doi: 10.1210/en.2008-0971. Epub 2009 Jan 22.
- Gao H, Bryzgalova G, Hedman E, Khan A, Efendic S, Gustafsson JA, Dahlman-Wright K. Long-term administration of estradiol decreases expression of hepatic lipogenic genes and improves insulin sensitivity in ob/ob mice: a possible mechanism is through direct regulation of signal transducer and activator of transcription 3. Mol Endocrinol. 2006 Jun;20(6):1287-99. doi: 10.1210/me.2006-0012. Epub 2006 Apr 20.
- Pasarica M, Sereda OR, Redman LM, Albarado DC, Hymel DT, Roan LE, Rood JC, Burk DH, Smith SR. Reduced adipose tissue oxygenation in human obesity: evidence for rarefaction, macrophage chemotaxis, and inflammation without an angiogenic response. Diabetes. 2009 Mar;58(3):718-25. doi: 10.2337/db08-1098. Epub 2008 Dec 15.
- Khan T, Muise ES, Iyengar P, Wang ZV, Chandalia M, Abate N, Zhang BB, Bonaldo P, Chua S, Scherer PE. Metabolic dysregulation and adipose tissue fibrosis: role of collagen VI. Mol Cell Biol. 2009 Mar;29(6):1575-91. doi: 10.1128/MCB.01300-08. Epub 2008 Dec 29.
- Haas E, Bhattacharya I, Brailoiu E, Damjanovic M, Brailoiu GC, Gao X, Mueller-Guerre L, Marjon NA, Gut A, Minotti R, Meyer MR, Amann K, Ammann E, Perez-Dominguez A, Genoni M, Clegg DJ, Dun NJ, Resta TC, Prossnitz ER, Barton M. Regulatory role of G protein-coupled estrogen receptor for vascular function and obesity. Circ Res. 2009 Feb 13;104(3):288-91. doi: 10.1161/CIRCRESAHA.108.190892. Epub 2009 Jan 29.
- Belanger C, Luu-The V, Dupont P, Tchernof A. Adipose tissue intracrinology: potential importance of local androgen/estrogen metabolism in the regulation of adiposity. Horm Metab Res. 2002 Nov-Dec;34(11-12):737-45. doi: 10.1055/s-2002-38265.
- Cleland WH, Mendelson CR, Simpson ER. Aromatase activity of membrane fractions of human adipose tissue stromal cells and adipocytes. Endocrinology. 1983 Dec;113(6):2155-60. doi: 10.1210/endo-113-6-2155.
- Brasaemle DL, Dolios G, Shapiro L, Wang R. Proteomic analysis of proteins associated with lipid droplets of basal and lipolytically stimulated 3T3-L1 adipocytes. J Biol Chem. 2004 Nov 5;279(45):46835-42. doi: 10.1074/jbc.M409340200. Epub 2004 Aug 27.
- Khor VK, Tong MH, Qian Y, Song WC. Gender-specific expression and mechanism of regulation of estrogen sulfotransferase in adipose tissues of the mouse. Endocrinology. 2008 Nov;149(11):5440-8. doi: 10.1210/en.2008-0271. Epub 2008 Jul 31.
- Marin P, Krotkiewski M, Bjorntorp P. Androgen treatment of middle-aged, obese men: effects on metabolism, muscle and adipose tissues. Eur J Med. 1992 Oct;1(6):329-36.
- Lovejoy JC, Champagne CM, de Jonge L, Xie H, Smith SR. Increased visceral fat and decreased energy expenditure during the menopausal transition. Int J Obes (Lond). 2008 Jun;32(6):949-58. doi: 10.1038/ijo.2008.25. Epub 2008 Mar 11.
- van Nas A, Guhathakurta D, Wang SS, Yehya N, Horvath S, Zhang B, Ingram-Drake L, Chaudhuri G, Schadt EE, Drake TA, Arnold AP, Lusis AJ. Elucidating the role of gonadal hormones in sexually dimorphic gene coexpression networks. Endocrinology. 2009 Mar;150(3):1235-49. doi: 10.1210/en.2008-0563. Epub 2008 Oct 30.
- Guo K, Mogen J, Struzzi S, Zhang Y. Preadipocyte transplantation: an in vivo study of direct leptin signaling on adipocyte morphogenesis and cell size. Am J Physiol Regul Integr Comp Physiol. 2009 May;296(5):R1339-47. doi: 10.1152/ajpregu.90691.2008. Epub 2009 Feb 4.
- Fabian MR, Sonenberg N, Filipowicz W. Regulation of mRNA translation and stability by microRNAs. Annu Rev Biochem. 2010;79:351-79. doi: 10.1146/annurev-biochem-060308-103103.
- Jones ME, Thorburn AW, Britt KL, Hewitt KN, Wreford NG, Proietto J, Oz OK, Leury BJ, Robertson KM, Yao S, Simpson ER. Aromatase-deficient (ArKO) mice have a phenotype of increased adiposity. Proc Natl Acad Sci U S A. 2000 Nov 7;97(23):12735-40. doi: 10.1073/pnas.97.23.12735.
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- Livingstone MB, Black AE. Markers of the validity of reported energy intake. J Nutr. 2003 Mar;133 Suppl 3:895S-920S. doi: 10.1093/jn/133.3.895S.
- Schoeller DA, Racette SB. A review of field techniques for the assessment of energy expenditure. J Nutr. 1990 Nov;120 Suppl 11(11 Suppl):1492-5. doi: 10.1093/jn/120.suppl_11.1492.
- Lavau M, Susini C, Knittle J, Blanchet-Hirst S, Greenwood MR. A reliable photomicrographic method to determining fat cell size and number: application to dietary obesity. Proc Soc Exp Biol Med. 1977 Nov;156(2):251-6. doi: 10.3181/00379727-156-39916. No abstract available.
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- Divoux A, Sandor K, Bojcsuk D, Talukder A, Li X, Balint BL, Osborne TF, Smith SR. Differential open chromatin profile and transcriptomic signature define depot-specific human subcutaneous preadipocytes: primary outcomes. Clin Epigenetics. 2018 Nov 26;10(1):148. doi: 10.1186/s13148-018-0582-0.
- Divoux A, Xie H, Li JL, Karastergiou K, Perera RJ, Chang RJ, Fried SK, Smith SR. MicroRNA-196 Regulates HOX Gene Expression in Human Gluteal Adipose Tissue. Obesity (Silver Spring). 2017 Aug;25(8):1375-1383. doi: 10.1002/oby.21896. Epub 2017 Jun 25.
- Gealekman O, Guseva N, Hartigan C, Apotheker S, Gorgoglione M, Gurav K, Tran KV, Straubhaar J, Nicoloro S, Czech MP, Thompson M, Perugini RA, Corvera S. Depot-specific differences and insufficient subcutaneous adipose tissue angiogenesis in human obesity. Circulation. 2011 Jan 18;123(2):186-94. doi: 10.1161/CIRCULATIONAHA.110.970145. Epub 2011 Jan 3.
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Faktiske)
Studieafslutning (Anslået)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Anslået)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
- Urogenitale sygdomme
- Genitale sygdomme
- Sygdomme i det endokrine system
- Patologiske processer
- Ernæringsforstyrrelser
- Neoplasmer
- Urogenitale sygdomme hos kvinder
- Kvinders urogenitale sygdomme og graviditetskomplikationer
- Overernæring
- Kropsvægt
- Sygdom
- Kønssygdomme, kvindelige
- Ovariesygdomme
- Adnexale sygdomme
- Gonadale lidelser
- Ovariecyster
- Cyster
- Overvægtig
- Syndrom
- Polycystisk ovariesyndrom
- Metaboliske sygdomme
Andre undersøgelses-id-numre
- TRIMDFH 348525
- 348525 (Anden identifikator: AdventHealth)
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
Studerer et amerikansk FDA-reguleret lægemiddelprodukt
Studerer et amerikansk FDA-reguleret enhedsprodukt
produkt fremstillet i og eksporteret fra U.S.A.
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