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CompletedNCT02548039Updated Aug 7, 2018

To Study The Influence Of Genomic Factors On Metabolism And Effects Of Clomiphene In Asian Normogonadotrophic Anovulatory Patients.

An observational study in Infertility, Female, sponsored by KK Women's and Children's Hospital. Completed at 1 site in Singapore. Open to female participants aged 21 Years to 43 Years. Per ClinicalTrials.gov, last updated 2018-08-07.

Sponsored by KK Women's and Children's Hospital · Observational

Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
124
Ages
21 Years to 43 Years
Sex
Female
01

Study summary

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.

Read the detailed description

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.

02

Conditions studied

  • Infertility, Female

Keywords

  • Anovulatory
  • Clomiphene
03

Who can participate

Ages eligible
21 Years to 43 Years
Sexes eligible
Female
Accepts healthy volunteers
No
Sampling method
Non-probability sample

Study population

Asian Normogonadotrophic Anovulatory Women

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

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)
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Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
124 participants (actual)
Patient registry
No
Biospecimen retention
Samples with dna

Groups and cohorts

  • Asian Normogonadotrophic Anovulatory Women

    Asian women with normal gonadotropin levels but do not ovulate.

05

What researchers measure

Primary outcomes

  1. Achievement of successful ovulation

    Successful ovulation is defined as a mid-luteal phase serum progesterone level of \>20 nmol/L.

    Time frame: Day 20-23 of menses cycle

06

Study locations

1 site
  • KK Women's and Children's Hospital
    Singapore, 229899, Singapore
07

References and documents

Publications

  • 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. PubMed 18445989 ↗
  • 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. PubMed 15136073 ↗
  • 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. PubMed 22108178 ↗

Individual participant data

Plan to share: Undecided

08

Registry details

Key details

Study ID
NCT02548039
Lead sponsor
KK Women's and Children's Hospital
Collaborators
National Cancer Centre, Singapore
Responsible party
Sponsor
First posted
Sep 14, 2015
Start date
Jan 2015
Primary completion
Mar 2017
Completion
May 2018
Last update
Aug 7, 2018

Study contacts

Jerry Chan, MB BCh BaO (Hons) MA,FRCOG,PhD
principal investigator · KK Women's and Children's Hospital

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Jun 2018. You cannot join it, but the record below documents what was studied.

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