|- candidate number||15904|
|- NTR Number||NTR4324|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||18-dec-2013|
|- Secondary IDs||11-301 METC UMC Utrecht|
|- Public Title||BRCA mutations and ovarian Ageing in normo-oVulAtory women|
|- Scientific Title||BRCA mutations and ovarian Ageing in normo-oVulAtory women|
|- ACRONYM||BRAVA |
|- hypothesis||The primary hypothesis is that normo-ovulatory women with a BRCA mutation have lower levels of AMH compared to normo-ovulatory BRCA mutation-negative women, with at least a difference of 0.40 ng/ml, suggesting an effect size of three years in menopausal age.|
|- Healt Condition(s) or Problem(s) studied||BRCA1/2, Anti-mullerian hormone, Ovarian ageing|
|- Inclusion criteria||- Female age between 18 and 45 years |
- Predictive genetic testing on BRCA mutation or a known BRCA carrier status
- Regular menstrual cycles (i.e. mean cycle length of 21-35 days, with the next menstrual period predictable within a 7 days time frame)
- Written informed consent
|- Exclusion criteria||- Surgical menopause (i.e. premenopausal hysterectomy and/or bilateral ovariectomy)|
- Ovarian surgery
- Chemo- or radiation therapy
- Human immunodeficiency virus (HIV) infection
- Known endocrine or autoimmune abnormalities (i.e. Cushing syndrome, type I Diabetes Mellitus, hypothyroidism, hyperprolactinemia, adrenal insufficiency, hypoparathyriodism, myasthenia gravis, rheumatoid arthritis, systemic lupus erythematosus)
- Known genetic abnormalities (structural or numerical abnormalities of the X-chromosome (i.e. Turner’s syndrome, fragile X syndrome), or abnormalities on human autosomal functionally relevant genes, others than a BRCA mutation, associated with primary ovarian insufficiency.
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||Single arm|
|- planned startdate ||13-jan-2012|
|- planned closingdate||13-jan-2015|
|- Target number of participants||240|
|- Primary outcome||age specific AMH levels|
|- Secondary outcome||Reproductive health/ outcome|
|- Timepoints||The aim is to screen and investigate a total of 120 BRCA mutation-positive and 120 BRCA mutation-negative women in a period of approximately 2.5 years. A half year is calculated for data analysis and publishing results, resulting in a total study duration of three years.|
|- Trial web site||N/A|
|- status||inclusion stopped: follow-up|
|- CONTACT FOR PUBLIC QUERIES||Prof. dr. F.J. Broekmans|
|- CONTACT for SCIENTIFIC QUERIES||Prof. dr. F.J. Broekmans|
|- Sponsor/Initiator ||University Medical Center Utrecht (UMCU)|
(Source(s) of Monetary or Material Support)
|- Brief summary||Rationale:
In the current study, by comparing serum anti-müllerian hormone (AMH) levels between cohorts of normo-ovulatory BRCA (BReast CAncer) mutation-positive women and normo-ovulatory controls, we will be able to study the effect of BRCA mutations on ovarian ageing. The primary hypothesis is that normo-ovulatory women with a BRCA mutation have lower levels of AMH compared to normo-ovulatory BRCA mutation-negative women, with at least a difference of 0.40 ng/ml, suggesting an effect size of three years in menopausal age.
To confirm whether a BRCA mutation is a determinant of advanced ovarian ageing.
A cross sectional multi-centre study will be performed, recruiting normo-ovulatory BRCA mutation-positive women as the case group and normo-ovulatory BRCA mutation-negative women as controls.
The study population will be recruited by using to different approaches, a prospective and retrospective recruitment. For the prospective approach, women with an age ranging between 18 and 45 years, who present at the department of Medical Genetics for predictive BRCA mutation screening, will be asked to participate. For the retrospective, women with a current age ranging between 18 and 45 years, and with a known BRCA mutation carrier status, who have had a predictive DNA-test at the department of Medical Genetics up to 5 years earlier, are asked to participate.
University Medical Centre (UMC) Utrecht, UMC Groningen and The Netherlands Cancer Institute/ Antoni van Leeuwenhoek Hospital, Amsterdam.
Intervention: Not applicable.
Main study endpoint:
The main study endpoint will be advanced ovarian ageing, which is primary measured by age specific AMH levels.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
Burden associated with participation in the study consists of taken a blood sample, and filling out a questionnaire. Participating may be of benefit to the included women as they will receive a VVV-voucher to the value of 15 euros after providing blood and sending a completed questionnaire. Thereby, retrospective recruited participants will receive a travel allowance as stated by the UMC Utrecht.
|- Main changes (audit trail)||26-jul-2014: "The intervention has been a blood sample from the start of the trial. Due to misinterpretation, this was first interpreted as a therapeutical item." - AB|
|- RECORD||18-dec-2013 - 17-mrt-2015|