Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000115639
Ethics application status
Approved
Date submitted
16/01/2023
Date registered
3/02/2023
Date last updated
3/02/2023
Date data sharing statement initially provided
3/02/2023
Type of registration
Retrospectively registered

Titles & IDs
Public title
The Microbiome in Liver Disease and Liver Cancer
Scientific title
The Role of the Microbiome in the Pathogenesis of Liver Disease and Liver Cancer
Secondary ID [1] 308707 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Liver Disease 328638 0
Liver Cirrhosis 328639 0
Liver Cancer 328640 0
Condition category
Condition code
Cancer 325651 325651 0 0
Liver

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
We are studying changes in the microbiome and metabolome of patients with liver disease. Participants enrolled in the study will provide blood, stool and oral samples every 6 months when attending routine clinic visits. A key component of the study is the collection of samples from participants with liver cirrhosis until the development of liver cancer. For this reason, participants will be enrolled in the study for a period of 5 years. For oral and stool samples, participants will receive a kit to take home with instructions on how to collect the samples. For oral sample collection, the kit will consist of a swab and a collection tube. Participants will be asked to brush the inside surfaces of their mouth with the swab. For stool sample collection, the provided kit contains a ColOff® specimen collector, which is a plastic sleeve for the toilet seat that allows hygienic collection of stool.

Two validated surveys on physical activity and diet will be administered via REDCap every 6 months. The Physical Activity Scale for the Elderly (PASE) will be used to assess physical activity of recruited participants. The Australian Eating Survey Food Frequency Questionnaire (AES FFQ) will be used to collect diet-related data to assess intake of the major food groups. The surveys can be completed at home and should not take longer than a total of 30 minutes to complete. Participating sites for the study include St George, Royal Prince Alfred, Nepean, John Hunter and three sites in Victoria (The Alfred, St Vincent’s and Austin Health).
Intervention code [1] 325170 0
Early Detection / Screening
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 333494 0
Identify compositional shifts in the microbiome of cirrhotic participants with liver cancer development using shotgun metagenomic sequencing of oral and stool samples.
Timepoint [1] 333494 0
Baseline followed by every 6 months until the onset of liver cancer.
Primary outcome [2] 333640 0
Identify functional shifts in the microbiome of cirrhotic participants with liver cancer development by performing metabolomic analyses (NMR spectroscopy, ultra-performance liquid-chromatography mass spectrometry) on blood and stool samples.
Timepoint [2] 333640 0
Baseline followed by every 6 months until the onset of liver cancer.
Primary outcome [3] 333681 0
Identify a microbial-related shift in the cytokine milieu in participants that develop liver cancer using the Bio-Plex Pro human cytokine assay kit on blood samples.
Timepoint [3] 333681 0
Baseline followed by every 6 months until the onset of liver cancer.
Secondary outcome [1] 417283 0
Nil.
Timepoint [1] 417283 0
Nil.

Eligibility
Key inclusion criteria
Patients over the age of 18; patients with chronic liver disease and primary liver cancer (HCC); patients under the care of the investigators of this study (or their associates) who routinely visit study sites for treatment or care; patients willing to provide informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Subjects aged < 18 years; other primary liver cancers (e.g., mixed hepatocellular carcinoma and cholangiocarcinoma); known gastrointestinal disease; previous gastrointestinal surgery.

Study design
Purpose
Duration
Selection
Timing
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
22/11/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
1000
Accrual to date
12
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC

Funding & Sponsors
Funding source category [1] 312930 0
Government body
Name [1] 312930 0
Medical Research Future Fund (NHMRC)
Country [1] 312930 0
Australia
Primary sponsor type
University
Name
University of New South Wales
Address
UNSW Sydney
High St
Kensington NSW 2052
Australia
Country
Australia
Secondary sponsor category [1] 314618 0
None
Name [1] 314618 0
Address [1] 314618 0
Country [1] 314618 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312203 0
South Eastern Sydney Local Health District
Ethics committee address [1] 312203 0
District Executive Unit, Sutherland Hospital & Community Health Service
Level 4, Corner The Kingsway and Kareena Road
Caringbah NSW 2229
Ethics committee country [1] 312203 0
Australia
Date submitted for ethics approval [1] 312203 0
Approval date [1] 312203 0
20/12/2022
Ethics approval number [1] 312203 0

Summary
Brief summary
This study aims to identify one or more liver cancer specific microbial based biomarkers using a range of blood, stool (faecal) and oral samples from people who have a confirmed diagnosis of primary liver cancer and people who are at high risk of developing liver cancer due to chronic liver disease.

Who is it for?
You may be eligible for this study if you are an adult aged 18 years or older who has been diagnosed with chronic liver disease and/or primary liver cancer.

Study details
All participants who choose to enrol in this study will be asked to provide blood, stool and oral samples at 6 month intervals for up to five years post-enrolment. The study investigators will aim to collect these samples during a routine scheduled clinic visit so that participants do not need to attend additional study visits.

It is hoped this research will identify and validate a liver cancer specific biomarker model for early diagnosis of liver cancer. If successful, tests for identified biomarkers may then be used to diagnose liver cancer earlier in at-risk patients, which may lead to better outcomes for future liver cancer patients.
Trial website
Trial related presentations / publications
Public notes
Sample collection for this study began under the Liver Biobank ethics of Royal Prince Alfred Hospital (2019/ETH06614).

Contacts
Principal investigator
Name 123834 0
A/Prof Amany Zekry
Address 123834 0
Department of Gastroenterology & Hepatology
Level 1 Burt Nielson Wing
St George Hospital
Gray Street
Kogarah
2217
NSW
Country 123834 0
Australia
Phone 123834 0
+61 2 9113 2817
Fax 123834 0
Email 123834 0
a.zekry@unsw.edu.au
Contact person for public queries
Name 123835 0
A/Prof Amany Zekry
Address 123835 0
Department of Gastroenterology & Hepatology
Level 1 Burt Nielson Wing
St George Hospital
Gray Street
Kogarah
2217
NSW
Country 123835 0
Australia
Phone 123835 0
+61 2 9113 2817
Fax 123835 0
Email 123835 0
a.zekry@unsw.edu.au
Contact person for scientific queries
Name 123836 0
A/Prof Amany Zekry
Address 123836 0
Department of Gastroenterology & Hepatology
Level 1 Burt Nielson Wing
St George Hospital
Gray Street
Kogarah
2217
NSW
Country 123836 0
Australia
Phone 123836 0
+61 2 9113 2817
Fax 123836 0
Email 123836 0
a.zekry@unsw.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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.