Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001164886
Ethics application status
Approved
Date submitted
13/01/2020
Date registered
27/08/2021
Date last updated
13/06/2024
Date data sharing statement initially provided
27/08/2021
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Randomised Controlled Feasibility Trial of the Mechanisms of the Fertility Enhancing Effect of Lipiodol in Women
Scientific title
A Randomised Controlled Feasibility Trial of the Mechanisms of the Fertility Enhancing Effect of Lipiodol in Women Undergoing Hysterectomy for Benign Gynaecological Disease
Secondary ID [1] 300244 0
Nil known
Universal Trial Number (UTN)
U1111-1246-3861
Trial acronym
MoFEEL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Subfertility 315804 0
Endometriosis 315805 0
Condition category
Condition code
Reproductive Health and Childbirth 314096 314096 0 0
Fertility including in vitro fertilisation
Renal and Urogenital 314202 314202 0 0
Other renal and urogenital disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Women of reproductive age (<50 years) and who have a regular cycle that suggests ovulation, who are due to undergo hysterectomy for benign gynaecologcical conditions, will be recruited into the study. Following ethical approval and in the context of fully informed and written consent, 45 women will be randomised to one of three groups (n = 15 per group) in one single block of n=45 in a parallel-group design.

In the follicular phase of the cycle prior to hysterectomy Group 1 will receive a Lipiodol hysterosalpingogram (HSG), Group 2 will receive a control water soluble contrast media HSG and Group 3 will receive no intervention.

The dose of administered Lipiodol will not exceed 10mL in each case for each patient, with the duration of administration being confined to time of HSG procedure only (once off use). The mode of administration is via instillation through the cervical canal into the cervix and follopian tubes via a hysterosalpingography (HSG) procedure.

The attending Radiologist/physician will determine the exact dose of administered Lipiodol at the time of a HSG procedure. The minimum dose of Lipiodol to be administered above 5mL (including dead-volume in catheter) and until Lipiodol spill through the fimbriae is visualised by attending specialist radiologist under flouroscopy. A participant’s HSG procedure can vary in length, depending on clinical conditions between patients, however is not expected to exceed 20 mins in duration. A specialist Radiologist will administer the HSG procedure. The mode of administration is via instillation through the cervical canal using either a) Leech Wilkinson Cannula, or b) Cook Ballloon HSG Catheter, or c) a Rocket HSG Catheter. The type of water soluble contrast media utilised will be either Telebrix Hystero or agitated saline (which ever method is preferred by the Radiologist and in accordance to local protocol for HSG). The water soluble contrast media will be administered as per the lipidol administration procedure, the minimum dose will be above 5mL.

All HSG procedures completed by the respective Radiologists in each center will follow a clearly stipulated protocol for HSG as described above. Any deviations will be recorded by the attending radiologist and reported immediately to the trial coordinator.
Intervention code [1] 316516 0
Treatment: Drugs
Comparator / control treatment
As specified above, Group 3 will recieved no intervention.
Control group
Active

Outcomes
Primary outcome [1] 322485 0
The impact of Lipiodol exposure on immune cells and factors within peripheral blood as assessed by blood venepuncture.
Timepoint [1] 322485 0
There are two blood venepunctures (20ml of blood collected on each occasion) at two time points: 1) prior to intervention on the day of pipelle sampling and 2) at the time of hysterectomy.
Primary outcome [2] 322588 0
The impact of Lipiodol exposure on amount of Treg cells present as assessed by serum assay (I.e. reg cell abundance, suppressive capacity and stability)
Timepoint [2] 322588 0
Assessment will take place prior to intervention on the day of pipelle sampling, at the timeat two time points: 1) prior to intervention on the day of pipelle sampling and 2) at the time of hysterectomy.
Primary outcome [3] 328537 0
The uterine and fallopian cellular function assessed by microRNA (molecular) evaluation of uterine and fallopian tissue taken for analysis, This is a composite primary outcome.
Timepoint [3] 328537 0
This analysis will be conducted from tissues collected and stored post hysterectomy surgery.
Secondary outcome [1] 378669 0
Impact of Lipiodol on endometrial microbiome as assessed by medical records.
Timepoint [1] 378669 0
Assessment will take place on days 4,5,6,7,8, 32,33,34,35, and 36 days post HSG prcoedure.

Eligibility
Key inclusion criteria
Women of reproductive age (<50 years) and who have a regular cycle that suggests ovulation, who are due to undergo hysterectomy for benign gynaecologcical conditions
Minimum age
18 Years
Maximum age
49 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion criteria are:
- Any fibroid larger than 10cm in maximum dimension; (this change was made after 2 participants were recruited and at the initial screening stages of the MoFEEL trial)
- Known Malignancy;
- Known carrier of organism(s) associated with sexually transmitted infection (STI);
- Women scheduled for purely vaginal hysterectomy.
Women will complete our modification of the standardised World Endometriosis Research Foundation Endometriosis Phenome Harmonisation Project (EPHect) patient questionnaire, which is appropriate for any woman with benign gynaecological disease entering a research trial.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
45 women will be randomised to one of three groups (n = 15 per group) in one single block of n=45 in a parallel-group design.

Allocation concealment will involve contacting the holder of the allocation schedule who was "off-site" or at central administration site (the trial coordinator).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Sequence generation will involve simple randomisation using a randomisation table from a statistic book.
Stratified allocation will be employed in this study, utilising factors that can be used for stratification include centre, age, gender or previous treatment.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Pharmacodynamics
Statistical methods / analysis
Fifteen per group is a typical number of participants in trials that might unearth important differences or non-significant trends in the key immune-biological variables under study. Certainly, this number of participants per group will be sufficient to give information about likely differences in magnitude between the different interventions and the variation of the chances for each variable within each group.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
6/09/2021
Actual
2/08/2021
Date of last participant enrolment
Anticipated
30/09/2024
Actual
Date of last data collection
Anticipated
31/05/2025
Actual
Sample size
Target
45
Accrual to date
45
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 15608 0
Flinders Medical Centre - Bedford Park
Recruitment postcode(s) [1] 29008 0
5042 - Bedford Park

Funding & Sponsors
Funding source category [1] 304670 0
Commercial sector/Industry
Name [1] 304670 0
Guerbet Australia Pty Ltd.
Country [1] 304670 0
Australia
Primary sponsor type
Individual
Name
Professor Neil Johnson
Address
University of Adelaide, Robinson Research Institute
Ground Floor, Norwich Centre, 55 King William St, North Adelaide SA 5006
Country
Australia
Secondary sponsor category [1] 304975 0
Individual
Name [1] 304975 0
Professor Sarah Robertson
Address [1] 304975 0
University of Adelaide, Robinson Research Institute
Ground Floor, Norwich Centre, 55 King William St, North Adelaide SA 5006
Country [1] 304975 0
Australia
Other collaborator category [1] 281132 0
Individual
Name [1] 281132 0
Mr Faizz Fattah
Address [1] 281132 0
University of Adelaide, Robinson Research Institute
Ground Floor, Norwich Centre, 55 King William St, North Adelaide SA 5006
Country [1] 281132 0
Australia
Other collaborator category [2] 281133 0
Individual
Name [2] 281133 0
Associate Professor Louise Hull
Address [2] 281133 0
University of Adelaide, Robinson Research Institute
Ground Floor, Norwich Centre, 55 King William St, North Adelaide SA 5006
Country [2] 281133 0
Australia
Other collaborator category [3] 281134 0
Individual
Name [3] 281134 0
Dr Bruno Radesic
Address [3] 281134 0
Flinders Medical Center, Flinders Drive, Bedford Park SA 5042
Country [3] 281134 0
Australia
Other collaborator category [4] 281135 0
Individual
Name [4] 281135 0
Dr Lachlan Moldenhauer
Address [4] 281135 0
University of Adelaide, Robinson Research Institute
Ground Floor, Norwich Centre, 55 King William St, North Adelaide SA 5006
Country [4] 281135 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305090 0
University of Adelaide Human Research Ethics Committee
Ethics committee address [1] 305090 0
Level 4, Rundle Mall Plaza, 50 Rundle Mall
THE UNIVERSITY OF ADELAIDE
5005 AUSTRALIA
Ethics committee country [1] 305090 0
Australia
Date submitted for ethics approval [1] 305090 0
25/02/2020
Approval date [1] 305090 0
28/07/2020
Ethics approval number [1] 305090 0
H-2020-135

Summary
Brief summary
Lipiodol, an oil soluble contrast medium (OSCM) has a clear fertility enhancing effect, but its mechanism of action is uncertain. This trial seeks to determine the feasibility, from both the clinical perspective and the laboratory perspective, of changes brought about by lipiodol within the endometrium, the fallopian tubes and the peritoneal lining. Establishing the variables within these tissues that demonstrate the trends of effect of largest magnitude when women who have had a lipiodol hysterosalpingogram (HSG) are compared to women who have had an HSG with a water soluble contrast medium (WSCM), and when women who have had a lipiodol HSG are compared to women who have had no intervention, is likely to point towards candidate mechanisms. This pilot randomised controlled trial (RCT) will then inform the feasibility of testing such variables in a definitive RCT of women with infertility that could, in the future, assess whether such changes are associated with a successful fertility outcome. Future RCTs examining the fertility efficacy of lipiodol could then endeavour to link fertility efficacy to the candidate mechanism as part of the entire RCT or within a cohort of women who form part of the overall RCT group, but in whom the mechanisms of lipiodol are also sought.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 99238 0
Prof Neil Johnson
Address 99238 0
Robinson Research Institute,
University of Adelaide
Ground Floor, Norwich Centre,
55 King William Street,
North Adelaide SA 5006
Country 99238 0
Australia
Phone 99238 0
+61 402563020
Fax 99238 0
Email 99238 0
[email protected]
Contact person for public queries
Name 99239 0
Prof Neil Johnson
Address 99239 0
Robinson Research Institute,
University of Adelaide
Ground Floor, Norwich Centre,
55 King William Street,
North Adelaide SA 5006
Country 99239 0
Australia
Phone 99239 0
+61 402563020
Fax 99239 0
Email 99239 0
[email protected]
Contact person for scientific queries
Name 99240 0
Prof Neil Johnson
Address 99240 0
Robinson Research Institute,
University of Adelaide
Ground Floor, Norwich Centre,
55 King William Street,
North Adelaide SA 5006
Country 99240 0
Australia
Phone 99240 0
+61 402563020
Fax 99240 0
Email 99240 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
IPD will not be shared due to sensitivity of patient data collected.


What supporting documents are/will be available?

No Supporting Document Provided



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.