Infertility, FemaleNCT02548039
To Study The Influence Of Genomic Factors On Metabolism And Effects Of Clomiphene In Asian Normogonadotrophic Anovulatory Patients.
An observational study of Infertility, Female, run by KK Women's and Children's Hospital at 1 site in Singapore.
Trial 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 more about this study
- Who is it for?
- Ages 21 to 43 years, women only
- Conditions the study is for
- Infertility, Female
- How many people
- 124 participants
- Where
- 1 siteSingapore
- Study dates
- Jan 2015to May 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 43 years
- Women only
- No healthy volunteers
- Adult
Study population: Asian Normogonadotrophic Anovulatory Women
Who may be able to join
- 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
Who cannot join
- 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)
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- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
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.
- Conditions
- Infertility, Female
- Keywords
- Anovulatory, Clomiphene
- Medical subject headings
- Infertility, Female, Anovulation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Asian Normogonadotrophic Anovulatory Women | Asian women with normal gonadotropin levels but do not ovulate. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Achievement of successful ovulation
Successful ovulation is defined as a mid-luteal phase serum progesterone level of >20 nmol/L.
Measured: Day 20-23 of menses cycle
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2015 (estimated)
- Study startJan 2015
- Primary completionMar 2017
- Study completionMay 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Infertility, FemaleStudies of the same condition, open and under way.
- More trials run by KK Women's and Children's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 124 participants (actual)
Sponsor and investigators
- Lead sponsor
- KK Women's and Children's Hospital
- Sponsor type
- Other government
- Collaborators
- National Cancer Centre, Singapore
- Responsible party
- Sponsor
- Investigators
- Jerry Chan, MB BCh BaO (Hons) MA,FRCOG,PhD, Principal investigator, KK Women's and Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02548039
- Sponsor's protocol ID
- 2014/RM/001
- Status last verified
- Jun 2018
- First submitted
- 8 Sep 2015
- Last updated
- 7 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
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 18445989Rostami-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 15136073Murdter 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
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- To Study The Influence Of Pharmacogenomics Factors On Pharmacokinetics And Pharmacodynamics Of Clomiphene In Asian Normogonadotrophic Anovulatory Patients.
- ClinicalTrials.gov ID
- NCT02548039
- Acronym / sponsor ID
- 2014/RM/001
- Conditions
- Infertility, Female
- Keywords
- Anovulatory, Clomiphene
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 124 participants (actual)
- Lead sponsor
- KK Women's and Children's HospitalOther government
- Collaborators
- National Cancer Centre, Singapore
- Study start
- Jan 2015
- Primary completion
- Mar 2017 (actual)
- Study completion
- May 2018 (actual)
- First posted
- 14 Sep 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Asian Normogonadotrophic Anovulatory Women | – | –Asian women with normal gonadotropin levels but do not ovulate. |
Who may qualify
- Ages
- 21 to 43 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- Asian Normogonadotrophic Anovulatory Women
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (11 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Achievement of successful ovulation
Time frame: Day 20-23 of menses cycle
Successful ovulation is defined as a mid-luteal phase serum progesterone level of >20 nmol/L.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2018.
- Background: PubMed 18445989Ghobadi 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.
- Background: PubMed 15136073Rostami-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.
- Background: PubMed 22108178Murdter 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jerry Chan, MB BCh BaO (Hons) MA,FRCOG,PhD principal investigator
KK Women's and Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Infertility, Female, run by KK Women's and Children's Hospital at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Achievement of successful ovulation (time frame: Day 20-23 of menses cycle). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02548039, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2018.