To Study The Influence Of Genomic Factors On Metabolism And Effects Of Clomiphene In Asian Normogonadotrophic Anovulatory Patients.
To Study The Influence Of Pharmacogenomics Factors On Pharmacokinetics And Pharmacodynamics Of Clomiphene In Asian Normogonadotrophic Anovulatory Patients.
The purpose of this study is to match the genetic component and clinical attributes of anovulatory patients with response to clomiphene treatment.
By improving our understanding on patient-specific clomiphene response will allow optimization of treatment, reduction of side-effects and shorten the time-to-pregnancy.
Studienübersicht
Status
Bedingungen
Detaillierte Beschreibung
Anovulation is the commonest cause for infertility, with clomiphene being the standard treatment. Pharmacogenetic causes of variability in the pharmacokinetics and pharmacodynamics of clomiphene is not well characterized in anovulatory Asian women. Although recent findings suggest that the pharmacokinetics and pharmacodynamics of clomiphene may be influenced by several polygenic pathways involving genes regulating its metabolism (CYP3A4, CYP3A5, CYP2B6, CYP2C8, CYP2C19, CYP2D6), thus contributing significantly to the wide variability in dose-response relationships observed in clinical practice. There has not been objective evidence thus far from an unbiased genome-wide perspective. It is likely that polymorphisms at the CYP cluster of genes encoding for their respective cytochrome proteins may not explain all of the variability with regards to clomiphene's dose-response relationship.
The investigators hypothesize that the pharmacokinetics and pharmacodynamics of clomiphene is under strong control by genetic loci and that these genetic variants could also strongly determine the therapeutic outcome in Asian normogonadotrophic anovulatory patients. The contribution by candidate genes mentioned above will also be clarified in a definitive manner by this study.
Studientyp
Einschreibung (Tatsächlich)
Kontakte und Standorte
Studienorte
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Singapore, Singapur, 229899
- KK Women's and Children's Hospital
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Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Probenahmeverfahren
Studienpopulation
Beschreibung
Inclusion Criteria:
- Women of reproductive age with ovulatory dysfunction desiring pregnancy,
- Willing to discontinue any form of herbal or traditional chinese medicines for at least three weeks before starting Clomiphene
- Ability to provide written and informed consent taken from participating patients, and
- Willingness to cooperate with study instructions
Exclusion Criteria:
- Pregnant at the time of recruitment,
- Ovarian cysts more than 5cm,
- Abnormal menorrhagia at the time of study recruitment,
- Abnormal liver function or active liver disease,
- Presence of neoplastic lesions of any type,
- Primary pituitary or ovarian failure (Type I and III World Health Organisation [WHO] Infertility)
- Patients with previous treatment with ovulation inducing agents such as follicle stimulating hormone (FSH) and luteinising hormone releasing hormone-analogues (LHRH-analogues);
- Infertility due to other endocrine abnormalities such as hyperprolactinaemia, hypo/hyperthyroidism, premature ovarian failure, diabetes or male factor
- Allergy to clomiphene.
- Fallopian tubal pathology (hydrosalpinges, previous salpingectomies)
- Patients on any drugs with potential to interact with CYP2D6 such as the selective serotonin receptor uptake inhibitors (ex. Venlafaxine, paroxitene, fluoxetine)
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Beobachtungsmodelle: Kohorte
- Zeitperspektiven: Interessent
Kohorten und Interventionen
Gruppe / Kohorte |
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Asian Normogonadotrophic Anovulatory Women
Asian women with normal gonadotropin levels but do not ovulate.
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Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
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Achievement of successful ovulation
Zeitfenster: Day 20-23 of menses cycle
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Successful ovulation is defined as a mid-luteal phase serum progesterone level of >20 nmol/L.
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Day 20-23 of menses cycle
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Mitarbeiter und Ermittler
Mitarbeiter
Ermittler
- Hauptermittler: Jerry Chan, MB BCh BaO (Hons) MA,FRCOG,PhD, KK Women's and Children's Hospital
Publikationen und hilfreiche Links
Allgemeine Veröffentlichungen
- Ghobadi C, Gregory A, Crewe HK, Rostami-Hodjegan A, Lennard MS. CYP2D6 is primarily responsible for the metabolism of clomiphene. Drug Metab Pharmacokinet. 2008;23(2):101-5. doi: 10.2133/dmpk.23.101.
- Rostami-Hodjegan A, Lennard MS, Tucker GT, Ledger WL. Monitoring plasma concentrations to individualize treatment with clomiphene citrate. Fertil Steril. 2004 May;81(5):1187-93. doi: 10.1016/j.fertnstert.2003.07.044.
- Murdter TE, Kerb R, Turpeinen M, Schroth W, Ganchev B, Bohmer GM, Igel S, Schaeffeler E, Zanger U, Brauch H, Schwab M. Genetic polymorphism of cytochrome P450 2D6 determines oestrogen receptor activity of the major infertility drug clomiphene via its active metabolites. Hum Mol Genet. 2012 Mar 1;21(5):1145-54. doi: 10.1093/hmg/ddr543. Epub 2011 Nov 22.
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn
Primärer Abschluss (Tatsächlich)
Studienabschluss (Tatsächlich)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Schätzen)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
Andere Studien-ID-Nummern
- 2014/RM/001
Plan für individuelle Teilnehmerdaten (IPD)
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Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
Produkt, das in den USA hergestellt und aus den USA exportiert wird
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