Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001579886
Ethics application status
Approved
Date submitted
5/09/2020
Date registered
18/11/2021
Date last updated
18/11/2021
Date data sharing statement initially provided
18/11/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Can a test be developed based on a biopsy of a woman's womb lining, that helps predict whether or not she has endometriosis?
A prospective case-control study of B-cell lymphoma 6 protein (BCL6), amongst women who are undertaking keyhole surgery.
Scientific title
B-cell lymphoma 6 protein (BCL6) as a potential biomarker for endometriosis: can it be used to predict endometriosis' presence and/or severity?
Secondary ID [1] 302205 0
None
Universal Trial Number (UTN)
U1111-1257-7253
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Endometriosis 318953 0
Condition category
Condition code
Reproductive Health and Childbirth 316926 316926 0 0
Other reproductive health and childbirth disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Women who fulfil the selection criteria will be invited to participate in the study. Many of these women will already be planned to undertake a concurrent endometrial biopsy (which takes approximately 5 minutes), at the time of their laparoscopy (which may take anything from 30 minutes to 4 hours). If not: we will talk them through a consent form for endometrial biopsy, using the standard dilatation and curettage method. If they agree to participate, their procedure will be booked to occur during the luteal phase of their menstrual cycle (i.e. the two weeks leading up to an expected period).
Patients will be asked to complete an online version of the long-form EHP-30 questionnaire pre-operatively. The EHP-30 is a reliable, validated instrument to measure the health-related quality of life of women with endometriosis. It asks participants (over the course of 30 questions) to recall how often in the last four weeks they have experienced various symptoms of endometriosis. The ‘long-form’ version includes six additional sections (using 23 questions) covering areas such as: work; relationships with children; sexual relationship(s); and feelings about the medical profession, treatment, and infertility.
At their planned procedure, endometrial biopsy will be taken, using the standard dilatation and curettage method. The endometrial biopsy sample will be sent to the laboratory for analysis of the BCL6 level. Laparoscopy will be undertaken (as planned) by trained gynaecologists, and the patient’s endometriosis (if present) will be scored. Clinicians will use the best-known, and most widely used, classification system for endometriosis: the revised American Society for Reproductive Medicine (r-ASRM) classification system. This involves documenting and scoring patients’ endometriotic implants (seen at laparoscopy) based on their location and size, the location and thickness of any adhesions (internal scarring), plus the extent to which the ‘Pouch of Douglas’ (the area between the uterus and bowel) is involved. Patients will then end up being classified as having either: no endometriosis; stage I (minimal); stage II (mild); stage III (moderate); or stage IV (severe) endometriosis.
Operation notes will be accessed as needed, to ensure adherence to the interventions.
Intervention code [1] 318530 0
Treatment: Surgery
Intervention code [2] 321556 0
Early detection / Screening
Comparator / control treatment
The control group will be made up of women who have laparoscopic surgery, and are not found to have any endometriosis during the procedure.
The control group will undertake the same interventions (endometrial biopsy). Like the cases, they will already be planning to undertake laparoscopic (keyhole) surgery, whether or not they participate in this research.
Control group
Active

Outcomes
Primary outcome [1] 325033 0
To evaluate BCL6 expression in luteal phase endometrial biopsy in women with and without endometriosis at laparoscopy.
Timepoint [1] 325033 0
On the day of their planned laparoscopic (keyhole) surgery; in the luteal phase of the participants' menstrual cycle.
Secondary outcome [1] 386596 0
Health-related quality of life assessed by the Endometriosis Health Profile Questionnaire (EHP-30) long-form
Timepoint [1] 386596 0
Participants will complete an EHP-30 questionnaire on the day of their laparoscopic (keyhole) surgery.
Secondary outcome [2] 386597 0
Severity of endometriosis assessed by the r-ASRM classification conducted during the laparascopic procedure
Timepoint [2] 386597 0
Participants will have their endometriosis assessed and classified on the day of their laparoscopic (keyhole) surgery.

Eligibility
Key inclusion criteria
- Women aged between 18 – 50yo
- Women who have a regular menstrual cycle (i.e. menstrual cycle length 21 - 35 days inclusive)
- Women who are already planning to undertake laparoscopy, for any indication
- English speaking
- Capacity and willingness to give written informed consent
- Willingness to comply with the study
- Willingness to have their planned procedure undertaken in the luteal phase of their menstrual cycle
Minimum age
18 Years
Maximum age
50 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- Women aged < 18yo or > 50yo
- Women with an irregular menstrual cycle (i.e. menstrual cycle length < 21 days or > 35 days)
- Women who have an absolute contra-indication to endometrial biopsy, such as viable (ongoing) intra-uterine pregnancy
- Women who have a relative contra-indication to endometrial biopsy, such as: active cervical or uterine infection
- Women in whom undertaking an (otherwise unnecessary) endometrial biopsy may worsen a pre-existing condition (e.g. Asherman’s syndrome, intra-uterine adhesions)

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
N/A
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Case-control study, based on prospectively-collected data.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Regarding participants’ answers to questions in the EHP-30 questionnaire: SurveyMonkey automatically exports data to statistical software SPSS, which will be used to perform the statistical analysis. Participants’ BCL6 levels will be uploaded into the relevant section of the SPSS document used for this research, as will participants’ endometriosis severity (based on the r-ASRM classification system).
Participants’ BCL6 results will be continuous data, with their BCL6 HSCORE ranging from 0 to 4. Participants’ endometriosis severity will be ordinal data, in that all participants will be categorised into one of five distinct groups: no endometriosis; stage I (minimal) endometriosis; stage II (mild) endometriosis; stage III (moderate) endometriosis; or stage IV (severe) endometriosis. It is expected that participants’ BCL6 results by endometriosis severity will be presented in a boxplot.
Receiver-operator characteristic analysis will be performed to assess the usefulness of the biomarker and to find the optimal cut-off score for BLC6 that differentiates best between cases and controls.
Statistical analysis will aim to determine to what extent patients’ BCL6 levels (on luteal phase endometrial biopsy) is predictive of the presence and severity of endometriosis at laparoscopy. Additional analysis will include patients’ EHP-30 results as a predictive variable, to assess if the combination of BCL6 level plus EHP-30 answers improves the predictive value of these two screening tools for endometriosis.
Students t test will be used to compare mean BLC6 levels between cases and controls.
Regarding participants’ EHP-30 questionnaire results: logistic regression analysis and a multi-variable model will enable us to ascertain whether including particular aspects of the long-form EHP-30 improves the predictive value of BCL6 in finding endometriosis at laparoscopy. If any such relationships are found, it is expected that these results could be presented as a nomogram, or classification tree analysis.
The statistical comparisons will be performed using statistical software SPSS (IBM) or similar, with P values < 0.05 considered significant.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
10/01/2022
Actual
Date of last participant enrolment
Anticipated
5/09/2022
Actual
Date of last data collection
Anticipated
7/11/2022
Actual
Sample size
Target
184
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 17440 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [2] 17441 0
North Shore Private Hospital - St Leonards
Recruitment hospital [3] 17443 0
Concord Repatriation Hospital - Concord
Recruitment hospital [4] 17444 0
Nepean Hospital - Kingswood
Recruitment hospital [5] 17445 0
Strathfield Private Hospital - Strathfield
Recruitment hospital [6] 17446 0
Mater Sydney - North Sydney
Recruitment hospital [7] 20351 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 31169 0
2065 - St Leonards
Recruitment postcode(s) [2] 31171 0
2139 - Concord
Recruitment postcode(s) [3] 31172 0
2747 - Kingswood
Recruitment postcode(s) [4] 31173 0
2135 - Strathfield
Recruitment postcode(s) [5] 31174 0
2060 - North Sydney
Recruitment postcode(s) [6] 35113 0
2050 - Camperdown
Recruitment postcode(s) [7] 35114 0
3260 - Camperdown

Funding & Sponsors
Funding source category [1] 306625 0
Commercial sector/Industry
Name [1] 306625 0
Douglass Hanly Moir Pathology
Country [1] 306625 0
Australia
Funding source category [2] 309538 0
Commercial sector/Industry
Name [2] 309538 0
Genea
Country [2] 309538 0
Australia
Primary sponsor type
Government body
Name
Northern Sydney Local Health District.
Address
Kolling Building
Level 14
10 Westbourne St
St Leonards, 2065
NSW
Country
Australia
Secondary sponsor category [1] 307155 0
Government body
Name [1] 307155 0
Sydney Local Health District
Address [1] 307155 0
Level 11
KGV Building
Missenden Road
CAMPERDOWN, 2050
NSW
Country [1] 307155 0
Australia
Secondary sponsor category [2] 310526 0
Hospital
Name [2] 310526 0
Nepean Blue Mountains Local Health District
Address [2] 310526 0
C/- Nepean Hospital
Derby Street
PENRITH NSW 2750
Country [2] 310526 0
Australia
Secondary sponsor category [3] 310527 0
Hospital
Name [3] 310527 0
St Vincent's Hospital
Address [3] 310527 0
390 Victoria Street
Darlinghurst, 2010
NSW
Country [3] 310527 0
Australia
Secondary sponsor category [4] 310528 0
Hospital
Name [4] 310528 0
North Shore Private Hospital
Address [4] 310528 0
Westbourne Street
ST LEONARDS, 2065
NSW
Country [4] 310528 0
Australia
Secondary sponsor category [5] 310529 0
Hospital
Name [5] 310529 0
Strathfield Private Hospital
Address [5] 310529 0
3-5 Everton Road
STRATHFIELD, 2135
NSW
Country [5] 310529 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306810 0
Northern Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 306810 0
Level 13
Kolling Building
Royal North Shore Hospital
Reserve Road
St Leonards, 2065
NSW
Ethics committee country [1] 306810 0
Australia
Date submitted for ethics approval [1] 306810 0
05/09/2020
Approval date [1] 306810 0
16/12/2020
Ethics approval number [1] 306810 0

Summary
Brief summary
This study will collect endometrial biopsies from women who are having laparoscopic surgery. During their operation, the presence +/- severity of a condition called 'endometriosis' will be graded.
We hope to see whether or not there is a correlation between 'BCL6' levels on their endometrial biopsy specimen, with the presence +/- severity of endometriosis at keyhole surgery.
Trial website
N/A
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 105090 0
Dr Alison Bryant-Smith
Address 105090 0
Centre for Advanced Reproductive Endosurgery
408 / 69 Christie St
St Leonards, 2065
NSW
Country 105090 0
Australia
Phone 105090 0
+61 2 9966 9121
Fax 105090 0
+61 2 9966 9126
Email 105090 0
[email protected]
Contact person for public queries
Name 105091 0
Dr Alison Bryant-Smith
Address 105091 0
Centre for Advanced Reproductive Endosurgery
408 / 69 Christie St
St Leonards, 2065
NSW
Country 105091 0
Australia
Phone 105091 0
+61 2 9966 9121
Fax 105091 0
+61 2 9966 9126
Email 105091 0
[email protected]
Contact person for scientific queries
Name 105092 0
Dr Alison Bryant-Smith
Address 105092 0
Centre for Advanced Reproductive Endosurgery
408 / 69 Christie St
St Leonards, 2065
NSW
Country 105092 0
Australia
Phone 105092 0
+61 2 9966 9121
Fax 105092 0
+61 2 9966 9126
Email 105092 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All data will be de-identified
The following data will be shared for all study participants:
- demographic data (eg. age)
- primary and secondary outcomes for individual patients (EHP-30 score, endometriosis stage, BCL6 result)
When will data be available (start and end dates)?
Data will be available following the completion of the data analysis for this study (approximately September 2022). Data will be retained for fifteen years, as mandated by our local ethics committee.
Available to whom?
Researchers who request it from the principal investigator.
Available for what types of analyses?
Confirmatory statistical analysis; for this study be replicated / vindicated by other research teams.
How or where can data be obtained?
By contacting the principal investigator, at [email protected]


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
13755Informed consent form    380508-(Uploaded-25-10-2021-13-09-51)-Study-related document.pdf
13756Informed consent form    380508-(Uploaded-25-10-2021-13-10-20)-Study-related document.pdf
13757Ethical approval    380508-(Uploaded-25-10-2021-13-12-22)-Study-related document.pdf
14160Study protocol    380508-(Uploaded-18-11-2021-14-06-55)-Study-related document.pdf



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.