Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12613000221752
Ethics application status
Approved
Date submitted
28/01/2013
Date registered
25/02/2013
Date last updated
25/02/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
Establishing an open access Biobank of human Fallopian tubes
Scientific title
Open Access Biobank of Human Fallopian Tubes: A prospective biomedical study of archived tissue samples to elucidate mechanisms of abnormal implantation including a molecular make-up of early maternal-embryonic interface, trophoblast proliferation and its paracrine/autocrine regulation in tubal ectopic pregnancy.
Secondary ID [1] 281809 0
Nil known
Universal Trial Number (UTN)
U1111-1138-7484
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Infertility
 288151 0
Tubal ectopic pregnancy 288154 0
Pathogenesis of abnormal implantation 288155 0
Carcinogenesis 288156 0
Condition category
Condition code
Reproductive Health and Childbirth 288518 288518 0 0
Fetal medicine and complications of pregnancy
Reproductive Health and Childbirth 288519 288519 0 0
Fertility including in vitro fertilisation
Cancer 288520 288520 0 0
Ovarian and primary peritoneal

Intervention/exposure
Study type
Observational
Patient registry
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
The project is a prospective biomedical study of archived specimens of Fallopian tube tissue and peripheral venous blood obtained from consented women age group from 21 to 50 years old who had salpingectomy for tubal ectopic pregnancy. A comparison group will include intact Fallopian tubes and peripheral blood samples from consented women of the same age group who underwent hysterectomy for non-malignant disease or tubal ligation for permanent contraception. All biological samples will be coupled to a detailed, anonymised medical history of each participant.

This project aims to address the lack of human samples for research in the areas of embryonic implantation and implantation failure, pathogenesis of ectopic pregnancy and understanding of malignant tissue invasion using trophoblast as a model system by establishing a collection of Fallopian tubes samples from patients undergoing surgical treatment of ectopic tubal pregnancy. This library of tissue and matched blood samples can then be interrogated using a variety of molecular techniques to improve understanding of regulation mechanisms of tissue receptivity to trophoblast invasion.
Protein and RNA analysis will be carried out on microdissected epithelial cells collected from the stored tubal specimens using laser capture microscopy (LCM).
The expression of the molecules of interest will be measured at the protein level by immunohistochemistry, Western blot and confocal microscopy. The gene expression of candidate molecules will be measured by RNA microarray and quantitative RT-PCR. Collected blood samples will be centrifuged 20 minutes following collection and the serum will be stored in aliquots (100 micro litres) at -20 degree Celsius till processed for ELISA to measure the concentrations of the molecules of interest.
Intervention code [1] 286357 0
Not applicable
Comparator / control treatment
The study group will include women diagnosed with tubal ectopic pregnancy and undergoing surgical treatment.
The comparison group will include women with healthy Fallopian tubes obtained at tubal ligation in the absence of a pregnancy or women with healthy Fallopian tubes undergoing a hysterectomy for other non-malignant diseases.
Control group
Active

Outcomes
Primary outcome [1] 288679 0
to create a bank of appropriately stored human Fallopian tube (FT) tissue from women with an unruptured ectopic pregnancy and from a healthy comparison group
Timepoint [1] 288679 0
2 years
Primary outcome [2] 288680 0
to reduce reliance on animal models which do not accurately mimic the human cellular phenotype and genotype, are costly and difficult to manage due to ethical dilemmas involved in animal research
Timepoint [2] 288680 0
2 years
Secondary outcome [1] 300752 0
a. to study the molecular basis of human embryonic implantation
Timepoint [1] 300752 0
Time point will be determined by utilization of the Biobank and tissue availability.
Secondary outcome [2] 301398 0
b. to elucidate the pathogenesis of infertility and implantation failure
Timepoint [2] 301398 0
Time point will be determined by utilization of the Biobank and tissue availability.
Secondary outcome [3] 301399 0
c. to investigate trophoblast invasion and a model for carcinogenesis
Timepoint [3] 301399 0
Time point will be determined by utilization of the Biobank and tissue availability.
Secondary outcome [4] 301400 0
d. to develop novel methods for early diagnosis and non-invasive treatment of ectopic pregnancy
Timepoint [4] 301400 0
Time point will be determined by utilization of the Biobank and tissue availability.
Secondary outcome [5] 301401 0
e. to investigate abnormal placentation leading to placental disorders(pre-eclampsia, placenta accrete later in a pregnancy)
Timepoint [5] 301401 0
Time point will be determined by utilization of the Biobank and tissue availability.

Eligibility
Key inclusion criteria
Inclusion criteria for study group:
Sex: female
Age range: 21- 50
Disease status: unruptured ectopic pregnancy with stable vital signs
Concomitant disease status:
Laboratory parameters: positive bHCG
Others: ultrasound
Willingness to give written or oral informed consent and willingness to participate to and comply with the study.
Ability to understand spoken and written English, able to consent for research.

The comparison group will include women having hysterectomy for benign disease
or a sterilization procedure
Minimum age
21 Years
Maximum age
50 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria for participants in study group:

Patients with a significant degree of pain due to ectopic pregnancy
Patients with unstable vital signs
Patients who expressed desire not to participate in research
Patients who unable to understand the requirements of the study

Exclusion criteria for participants in comparison group:

Patients who are not willing to participate in research
Patients who are not able to give written informed consent.

Study design
Purpose
Duration
Selection
Timing
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
26/02/2013
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
150
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 454 0
Royal Hospital for Women - Randwick
Recruitment hospital [2] 455 0
Wollongong Hospital - Wollongong
Recruitment postcode(s) [1] 6209 0
2031 - Randwick
Recruitment postcode(s) [2] 6210 0
2500 - Wollongong

Funding & Sponsors
Funding source category [1] 286599 0
Government body
Name [1] 286599 0
National Health and Medical Research Council
Country [1] 286599 0
Australia
Primary sponsor type
Government body
Name
NHMRC
Address
National Health and Medical Research Council
Level 1; 16 Marcus Clarke Street
Canberra ACT 2601

Postal address: GPO Box 1421
Canberra ACT 2601
Country
Australia
Secondary sponsor category [1] 285385 0
Charities/Societies/Foundations
Name [1] 285385 0
Royal Hospital for Women Foundation
Address [1] 285385 0
RHW Foundation
Locked Bag 2000
Randwick NSW 2031
Country [1] 285385 0
Australia
Secondary sponsor category [2] 285386 0
Other Collaborative groups
Name [2] 285386 0
MAWA trust
Address [2] 285386 0
The MAWA Trust
PO Box 4203
Weston Creek
ACT 2611
Country [2] 285386 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288672 0
SESIAHS LHD HREC- Northern Sector
Ethics committee address [1] 288672 0
Prince of Wales Hospital
G71, East Wing, Edmund Blacket Building
Cnr High & Avoca Streets
Randwick NSW 2031
Ethics committee country [1] 288672 0
Australia
Date submitted for ethics approval [1] 288672 0
30/03/2012
Approval date [1] 288672 0
15/09/2012
Ethics approval number [1] 288672 0
12/055 (HREC/12/POWH/105)

Summary
Brief summary
Ectopic pregnancy is an unpredictable, non-viable and potentially life-threatening condition caused by ectopic (abnormal) implantation of an early embryo into the Fallopian tube instead of the uterus (womb). Ectopic pregnancy occurs in about 2% of pregnancies in Australia.
Recent research by our group and others has suggested possible reasons for the embryo failing to implant in the correct place in ectopic pregnancy. To allow us to study this further, we are setting up a bank of stored Fallopian tube tissue collected from women who are having the tube removed as treatment for an ectopic pregnancy. To study possible causes of miscarriage and infertility we will compare affected Fallopian tubes to healthy Fallopian tubes obtained from women who are having operation for non-malignant disease or tubal ligation. A Fallopian tube removed during surgery is not usually kept once it has been examined for diagnosis.
We have set up a process by which we can collect and appropriately store the tissue after it is examined by the pathologist.

The Biobank of human Fallopian tubes, a repository of disease-specific human samples will promote cutting edge biomedical research in the area of fertility, early embryogenesis and implantation, human reproduction, and carcinogenesis by decreasing reliance on animal models and allowing open access to human samples for scientists. The open access Biobank of human Fallopian tubes will facilitate data dissemination and will help to generate more studies refining methodologies in human research.
Trial website
Trial related presentations / publications
Presentations:
November 2012 Presentation at 10th Australasian Biobanking Network Association (ABNA) meeting, Hobart, Tasmania
"Exploring an opportunity of establishing a biobank in Australia"
September 2012 Poster presentation at the Annual Scientific Meeting 2012, RANZCOG, Canberra "Capital Gains in Women Health"

Publications:
November 2012 Abstract of presentation "Exploring an opportunity of establishing a Biobank in Australia" in a Conference Handbook at 10th Australasian Biobanking Network Association (ABNA) meeting, Hobart, Tasmania

September 2012 Abstract of poster presentation in a "Capital Gains in Women Health" Conference Handbook at the Annual Scientific Meeting 2012, RANZCOG.

Refaat B, Ledger WL. The expression of activins, their type II receptors and follistatin in human Fallopian tube during the menstrual cycle and in pseudo-pregnancy. Human Reproduction, Vol 26, No 12 pp 3346-3354,2011

Al-Azemi M, Refaat B, Alpin J, Ledger W. The expression of MUCI in human Fallopian tube during the menstrual cycle and in ectopic pregnancy. Human Reproduction 2009;24:2582-2587

Al-Azemi M, Refaat B, Amer S, Ola B, Chapman N, Ledger W. The expression of inducible nitric oxide synthase in human Fallopian tube during the menstrual cycle and in ectopic pregnancy. Fertility and Sterility 2010;94:833-840

Bahathiq AO, Stewart RL, Wells M, Moore HD, Pacey AA, Ledger WL. Production of activins by the human endosalpinx. J Clin Endocriol Metab 2002;87:5283-5289

Bahathiq AO, Stewart RL, Baxter L, Wells M, Moore HD, Ledger WL. Tissue immunoexpression and messenger ribonucleic acid localization of inhibin/activin subunit in human epididymis. Fertility and Sterility 2005;83:78-85

Refaat BA, Bahathiq AO, Sockanathan S, Stewart RL, Wells M, Ledger WL. Production and localization of activins and activin type IIA and IIB receptors by the human endosalpinx. Reproduction 2004;128:249-255

Refaat B, Amer S, Ola B, Chapman N, Ledger W. The expression of activin-beta A and betaB-subunits, follistatin and active type II receptors in Fallopian tubes bearing an ectopic pregnancy. J Clin Endocrinol Metab 2008;93:293-299.

Refaat B, Al-Azemi M, Geary I, Eley A, Ledger W. Role of activins and inducible nitric oxide in the pathogenesis of ectopic pregnancy in patients with or without Chlamidia trachomatis infection. Clin Vaccine Immunol 2009;16:1493-1503
Public notes

Contacts
Principal investigator
Name 37202 0
Prof William L. Ledger
Address 37202 0
Level 1, Royal Hospital for Women, Barker Street (Locked Bag 2000), RANDWICK NSW 2031
Country 37202 0
Australia
Phone 37202 0
+61 2 9382 6515
Fax 37202 0
+61 2 9382 6444
Email 37202 0
[email protected]
Contact person for public queries
Name 37203 0
Dr Tatiana Zandanova
Address 37203 0
Level 1, Royal Hospital for Women, Barker Street (Locked Bag 2000), RANDWICK NSW 2031
Country 37203 0
Australia
Phone 37203 0
+61 422447270
Fax 37203 0
+61 2 9382 6444
Email 37203 0
[email protected]
Contact person for scientific queries
Name 37204 0
Dr Tatiana Zandanova
Address 37204 0
Level 1, Royal Hospital for Women, Barker Street (Locked Bag 2000), RANDWICK NSW 2031
Country 37204 0
Australia
Phone 37204 0
+61 422447270
Fax 37204 0
+61 2 9382 6444
Email 37204 0
[email protected]

No information has been provided regarding IPD availability


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.