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Trial registered on ANZCTR


Registration number
ACTRN12615000875505
Ethics application status
Approved
Date submitted
3/08/2015
Date registered
21/08/2015
Date last updated
25/06/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Non-invasive diagnosis and monitoring of non-alcoholic fatty liver disease in bariatric surgical patients
Scientific title
Efficacy of non-invasive tests in diagnosing and monitoring NAFLD in adult bariatric surgical patients
Secondary ID [1] 287201 0
Nil
Universal Trial Number (UTN)
U1111-1172-6277
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obesity 295789 0
Non-alcoholic fatty liver disease
295790 0
Bariatric surgery
295850 0
Condition category
Condition code
Diet and Nutrition 296059 296059 0 0
Obesity
Oral and Gastrointestinal 296060 296060 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Surgery 296104 296104 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
MAGNETIC RESONANCE SPECTROSCOPY (MRS)
This is an MRI scan, where the patient lies flat on a platform which is moved through the MRI tunnel. The procedure takes approximately 30 minutes and is carried out by the radiographer. The test is performed at baseline, and follow-up MRS is performed at 1 year after bariatric surgery. Patients will be seen in clinic prior to their scans to arrange a suitable time. Attendance will be checked by the study investigator and rescheduled if required.

TRANSIENT ELASTOGRAPHY/FIBROSCAN
This test looks at liver stiffness. Patients are scheduled for 3 scans during their year long follow-up (baseline, 3 and 12 months after bariatric surgery). The scan is performed in an outpatient clinic, with a probe on the right upper abdomen, similar to an ultrasound. The procedure takes approximately 10 minutes. It is not painful and there are no risks. The procedure is performed by trained Gastroenterologists. Attendance will be checked by the study investigator and rescheduled if required.

SERUM BIOMARKERS
Blood tests are taken from the patient at 0, 1, 3 and 12 months after bariatric surgery at their scheduled outpatient appointments. Approximately 20-30ml of blood will be taken at each time point. Tests of interest include routine blood tests, as well as the novel biomarker TNFSF14 (LIGHT) and other circulating cytokines.

BARIATRIC SURGERY
Surgery will occur as planned by their treating team.
Intervention code [1] 292485 0
Diagnosis / Prognosis
Comparator / control treatment
LIVER BIOPSY - INTRAOPERATIVE
Patients who are already undergoing elective bariatric surgery will be invited to participate. They will undergo bariatric surgery regardless of participation in this study. The liver biopsy will be taken during bariatric surgery under vision by their treating surgeon. Core biopsies as well as a small wedge biopsy will be taken. This amounts to a total of less than 1cm^3 of liver tissue. A liver biopsy is usually only performed during bariatric surgery if there are (1) pre-operative indications of liver disease or (2) intraoperative suspicion of liver disease. Not all patients would normally have routine liver biopsies.
The liver biopsies will be used for standard histopathology reporting (quantification of steatosis, fibrosis and inflammation), as well as processed to look specifically for immune cell infiltrates characterised by markers such as CD4, CD8 and LIGHT.

LIVER BIOPSY - PERCUTANEOUS
Patients with >33% steatosis, any inflammation or any fibrosis will be offered a follow-up liver biopsy at 12 months. They will be seen prior to this to reconsent for the procedure.
This will be performed under local anaesthetic in the Radiology Department by an experienced radiologist under ultrasound guidance. Two to three core biopsies will be taken. They will be sent for routine histopathology.

FAT BIOPSY
Visceral and subcutaneous fat will be taken during the operation from the omentum around the area of surgery, and from the incisions in the abdomen. This will be for analysis of inflammatory/immune mediators and cytokines.
Approximately 1cm cube of tissue will be taken from each of the adipose regions (visceral and subcutaneous).
Control group
Active

Outcomes
Primary outcome [1] 295730 0
Efficacy of transient elastography in measuring NAFLD in the bariatric cohort by comparison with liver biopsy
Timepoint [1] 295730 0
Baseline (around time of bariatric surgery - comparing to intraoperative liver biopsy), 3 months and 1 year (comparing to percutaneous liver biopsy)
Primary outcome [2] 295732 0
Efficacy of MR spectroscopy in measuring NAFLD in the bariatric cohort by comparison to liver biopsy
Timepoint [2] 295732 0
Baseline (comparing to intraoperative liver biopsy) and 1 year (comparing to percutaneous liver biopsy)
Primary outcome [3] 295733 0
Efficacy of serum biomarkers in measuring NAFLD in the bariatric cohort by comparison to liver biopsy
Timepoint [3] 295733 0
Baseline (comparing to intraoperative liver biopsy), 1 month, 3 months and 1 year (comparing to percutaneous liver biopsy)
Secondary outcome [1] 316349 0
Change in NAFLD with surgically induced weight loss as measured by liver biopsy
Timepoint [1] 316349 0
Baseline and 1 year
Secondary outcome [2] 316741 0
Correlation of mRNA profile of adipose tissue with liver biopsy in patients with NAFLD.
Timepoint [2] 316741 0
Baseline

Eligibility
Key inclusion criteria
Patients >17 years undergoing bariatric surgery and any of:
- AST or ALT > 0.5 upper limit normal
- GGT > upper limit normal
- Abnormal transient elastography
- Abnormal ultrasound suggesting NAFLD
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Other cause of liver disease
Past or current excessive ETOH

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)
Consecutive patients undergoing bariatric surgery who meet inclusion criteria will be invited to participate.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The sample size (for a study of diagnostic accuracy) has been powered to a previously noted sensitivity of approximately 0.85 with lower confidence limit of 0.7. This requires a case population of approximately 70 patients. With a prevalence of NAFLD of 90% in the population, the required number of patients is 95 (Flahaut, J Clin Epi, 58:859-62).

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 291768 0
Charities/Societies/Foundations
Name [1] 291768 0
The Alfred Research Trust
Address [1] 291768 0
99 Commercial Road
Prahran
Victoria, 3181
Country [1] 291768 0
Australia
Funding source category [2] 291769 0
University
Name [2] 291769 0
Centre for Obesity Research and Education, Monash University
Address [2] 291769 0
Level 6, The Alfred Centre
99 Commercial Road
Prahran,
Victoria, 3181
Country [2] 291769 0
Australia
Primary sponsor type
University
Name
Centre for Obesity Research and Education, Monash University
Address
Level 6, The Alfred Centre
99 Commercial Road
Prahran,
Victoria, 3181
Country
Australia
Secondary sponsor category [1] 290436 0
Hospital
Name [1] 290436 0
Department of Gastroenterology and Department of Upper Gastrointestinal Surgery, The Alfred Hospital

Address [1] 290436 0
99 Commercial Road,
Prahran
Victoria 3181
Country [1] 290436 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293287 0
The Alfred HREC
Ethics committee address [1] 293287 0
99 Commercial Road,
Prahran
Victoria 3181
Ethics committee country [1] 293287 0
Australia
Date submitted for ethics approval [1] 293287 0
Approval date [1] 293287 0
09/06/2015
Ethics approval number [1] 293287 0
195/15
Ethics committee name [2] 293288 0
Monash University HREC
Ethics committee address [2] 293288 0
Monash University
Room 111, Chancellery Building E
24 Sports Walk, Clayton Campus
Wellington Road, Clayton, Victoria, 3800
Ethics committee country [2] 293288 0
Australia
Date submitted for ethics approval [2] 293288 0
Approval date [2] 293288 0
17/07/2015
Ethics approval number [2] 293288 0
CF15/2419-2015000971

Summary
Brief summary
This is a prospective cohort study for patients undergoing bariatric surgery who have risk factors for NAFLD, to investigate efficacy of non-invasive tests in diagnosing and monitoring NAFLD.
Patients who are already scheduled for bariatric surgery who fit criteria for likely NAFLD will be recruited to undergo an intraoperative liver and adipose tissue biopsy. Each participant will be required to attend regular follow-up appointments (0, 1, 3, and 12 months), blood tests (0, 1, 3 and 12 months), FibroScan (0, 3 and 12 months) and MRS (0 and 12 months) over a 12-month study period. Patients with significant liver disease on initial biopsy (NAFLD activity score (NAS) greater than 4, any fibrosis, any inflammation or greater than 33% steatosis) will be offered a follow-up liver biopsy at 12-months post-operatively.
Liver tissues and serum will be investigated for markers that may indicate disease presence and prognosis.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 59262 0
Dr Geraldine Ooi
Address 59262 0
Centre for Obesity Research and Education, Monash University
Level 6, The Alfred Centre
99 Commercial Road, Prahran
Victoria, 3181
Country 59262 0
Australia
Phone 59262 0
+613 9903 0725
Fax 59262 0
Email 59262 0
geraldineooi@gmail.com
Contact person for public queries
Name 59263 0
Dr Geraldine Ooi
Address 59263 0
Centre for Obesity Research and Education, Monash University
Level 6, The Alfred Centre
99 Commercial Road, Prahran
Victoria, 3181
Country 59263 0
Australia
Phone 59263 0
+613 9903 0725
Fax 59263 0
Email 59263 0
geraldineooi@gmail.com
Contact person for scientific queries
Name 59264 0
Dr Geraldine Ooi
Address 59264 0
Centre for Obesity Research and Education, Monash University
Level 6, The Alfred Centre
99 Commercial Road, Prahran
Victoria, 3181
Country 59264 0
Australia
Phone 59264 0
+613 9903 0725
Fax 59264 0
Email 59264 0
geraldineooi@gmail.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary