Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618001888257
Ethics application status
Approved
Date submitted
11/10/2018
Date registered
20/11/2018
Date last updated
20/11/2018
Date data sharing statement initially provided
20/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Effects on Non-Alcoholic Steato-Hepatitis (NASH) liver disease, obesity-associated metabolic
disturbances, weight loss, safety and quality of life in adults with NASH and obesity undergoing endoscopic sleeve gastroplasty.
Scientific title
Endoscopic Sleeve Gastroplasty (ESG) for obesity complicated by non­-alcoholic steato­hepatitis (NASH) +/­ type  two diabetes mellitus: A feasibility study.
Secondary ID [1] 295800 0
None
Universal Trial Number (UTN)
U1111-1222-0536
Trial acronym
E.O.N. (Endoscopic sleeve gastroplasty for Obesity complicated by NASH)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-alcoholic fatty liver disease 309262 0
obesity 309263 0
Condition category
Condition code
Metabolic and Endocrine 308135 308135 0 0
Metabolic disorders
Diet and Nutrition 308935 308935 0 0
Obesity
Oral and Gastrointestinal 308936 308936 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
EON (Endoscopic sleeve gastroplasty for Obesity complicated by NASH) Study is a feasibility study of endoscopic sleeve gastroplasty to evaluate the impact of this procedure on participants’ NASH liver disease and metabolic status.

NASH is an increasingly prevalent cause of advanced liver disease, which is associated with the Metabolic syndrome and its risks of diabetes mellitus and cardiovascular disease. There is presently no medical therapy for NASH. While lifestyle intervention is the mainstay of management most patients do not achieve or maintain their dietary goals or weight loss.

Bariatric surgery improves hepatic steatosis and liver tests. It also improves type 2 diabetes mellitus and may improve hepatic inflammation and fibrosis associated with NASH. Despite the increasing prevalence of obesity and the long-term benefits of bariatric surgery the incidence of procedures has plateaued since 2008; this may be because of the risk of surgical complications and the frequent need for hospital admission. Endoscopic surgery allows abdominal operations to be performed through the mouth, avoiding external incisions or scars. The endoscopic sleeve gastroplasty (ESG) procedure is an alternative to conventional surgical sleeve gastrectomy. ESG may lead to improvements in hepatic steatosis, inflammation and fibrosis, and in metabolic perturbations present in individuals who are obese and have NASH liver disease, with less complications than associated with conventional surgery.

As part of the EON Study, endoscopic sleeve gastroplasty (ESG) will be performed using a technique described by Abu Dayyeh et al. (Abu Dayyeh BK, Acosta A, Camilleri M et al. Clinical Gastroenterology Hepatology 2016; dx.doi.org/10.1016/j.cgh.2015.12.030) Patients will receive intra-procedural sub cutaneous heparin (5000IU).
A standard upper endoscope (GIF-H190; Olympus Australia, Notting Hill, VIC) will be used to examine the oesophagus and stomach for any anatomic contraindications. The procedure will be performed with the patient under general anaesthesia and with carbon dioxide insufflation. The procedure will be performed as a day-case procedure with participants being discharged home following recovery in the endoscopy recovery area.
An oesophageal overtube will be placed, and then 3 parallel suture placement sites (anterior, greater curvature, and posterior) lines will be marked by using argon plasma coagulation starting at the incisura and extending proximally to the gastro-oesophageal junction.
ESG will be created by using an interrupted triangular suture pattern that invaginates the greater curvature of the stomach to reduce the functional capacity of the stomach by 80%.
A second layer of sutures will be placed over the length of the central sleeve in an interrupted pattern to further reduce the gastric volume and reinforce the sleeve. The sutures will be full thickness, enabled by a tissue screw that captures the muscularis propria, avoiding gastric wall delamination. The tissue screw is part of the EndoStitch endoscopic suturing device that will be attached to the endoscope (OverStitch endoscopic suturing system; Apollo Endosurgery, Austin, Texas, USA).
Participants’ post-procedural diet will consist of liquid protein shakes for 4 weeks, then 2 weeks of a pureed diet before transitioning to a regular diet. The post-procedural diet will provide 70g of protein and 1000-1200 calories per day.
Repeat upper endoscopy will be performed at 3 months to evaluate ESG durability.

Before undergoing the study, intervention participants will undergo liver and metabolic evaluations, physical examination and psychological evaluation. Participants will undergo nutritional assessment and receive specific education on post-procedural diet with a clinical dietician.
Following the intervention subjects will be followed up until week 48 end-of-study clinical evaluations. There will be clinical assessments at weeks 4, 12, 24 and 36 post-intervention. There will be questionnaires to screen for adverse events at weeks 4, 8, 12, 24 and 36. The end-of study evaluations will assess the impact of the intervention of participants’ liver, metabolic, nutritional status and quality of life. End-of study evaluations include liver biopsy, blood and urine tests, medical and dietician clinical assessments and a quality of life questionnaire.

The ESG intervention will be performed by a specialist gastroenterologist with additional training and extensive expertise in interventional endoscopy. The procedure will be provided with the support of gastroenterology endoscopy nursing and specialist anaesthetist staff. Clinical assessments will be performed by a specialist gastroenterologist/ hepatologist, clinical dietician or nurse member of the investigating team.
The procedure will take place in the Gastroenterology endoscopy unit at Lyell McEwin Hospital Adelaide. Clinical assessments and follow-up will take place in the Department of Gastroenterology & Hepatology, Department of Clinical Nutrition, Department of Endocrinology or Clinical Trials Unit at Lyell McEwin Hospital Adelaide.
Intervention code [1] 312281 0
Treatment: Surgery
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 307724 0
NASH liver disease as assessed by improvement in liver histology (defined as resolution of steato-hepatitis without worsening of fibrosis, using the NAFLD Activity Score and Kleiner fibrosis classification of liver fibrosis), and by serum liver function tests.
Timepoint [1] 307724 0
Blood tests at weeks 24 and 48 post-ESG procedure. Liver biopsy at week 48 post-ESG procedure.
Primary outcome [2] 307898 0
Composite outcome of change in metabolic status (insulin resistance or glycaemic control, urinary albuminuria, lipid profiles) and blood pressure as assessed by HOMA-IR, HbA1c, fasting serum glucose and insulin, total cholesterol, HDL, LDL, triglycerides, urinary albumin: creatinine ratio. Systolic and diastolic blood pressure (mmHg) recorded using a digital blood pressure monitor..
Timepoint [2] 307898 0
Week 48 post-ESG intervention.
Primary outcome [3] 307899 0
Composite outcome of change in weight/ improvement of obesity as assessed by digital scale, calculation of body mass index.
Timepoint [3] 307899 0
Measurement of weight and calculation of body mass index at weeks 12, 24, 36 and 48 post-ESG procedure.
Secondary outcome [1] 352653 0
Health-related quality of life as assessed by SF36 score.
Timepoint [1] 352653 0
Week 48 following ESG procedure.
Secondary outcome [2] 353271 0
Incidence of adverse clinical events arising following ESG procedure, such as venous thromboembolism, re-intervention or unplanned hospital admissions. This will be assessed at week 4 post-ESG with a modified version of the World Health Organisation "RF1" patient safety Adverse Event Detection Questionnaire, and at weeks 8, 12, 24, 36 and 48 using a study-specific adverse event screening tool.

assessed using ICH/ FDA classification of adverse events in clinical trials (“Clinical safety data management: Definitions and standards for expedited reporting.” United States Food and Drug Administration; 1995 ).
Timepoint [2] 353271 0
Week 0 collection of ESG procedure data, questionnaires at weeks 4, 8, 12, 24, 36, and week 48 clinical assessment.

Eligibility
Key inclusion criteria
Obesity (body mass index) of greater than or equal to 35kg/m2, and up to 45kg/m2.
Diagnosis of non-alcoholic steato-hepatitis (NASH) based on liver biopsy.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
-Cirrhosis
-Significant alcohol consumption (>20g/day females, >30g/day males)
-Other causes of liver disease (untreated viral hepatitis, auto-immune hepatitis)
-Other significant medical morbidity associated with a poor long term prognosis or high pre-procedural risk. (This includes a history of previous unprovoked deep vein thrombosis or pulmonary embolism.)
-Anti-coagulation
-Use of medications that may affect the natural history of NAFLD/ NASH (obeticholic acid, pioglitazone, incretin mimetics, such as liraglutide; SGLT-2 inhibitors).
-History of previous gastric or oesophageal surgery, gastric ulcer, hiatus hernia >5cm.
-Pregnancy. (Where applicable) female subjects should avoid pregnancy pre-operatively and for 12 to 18 months post-operatively.
-Current active psychiatric illness, substance abuse or dependence.
-Presence of chronic, un-evaluated abdominal pain symptoms.
-Unwilling to consent to study requirements for monitoring and follow up.

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



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
For this feasibility study data will be expressed as medians with inter-quartile ranges, or as means with standard deviation.
No power calculation is required.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
26/11/2018
Actual
Date of last participant enrolment
Anticipated
20/12/2019
Actual
Date of last data collection
Anticipated
18/12/2020
Actual
Sample size
Target
10
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 12139 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment postcode(s) [1] 24483 0
5112 - Elizabeth Vale

Funding & Sponsors
Funding source category [1] 300391 0
Hospital
Name [1] 300391 0
Lyell McEwin Hospital Department of Gastroenterology & Hepatology research funds
Country [1] 300391 0
Australia
Primary sponsor type
Individual
Name
Dr Damian Harding (Chief researcher)
Address
Department of Gastroenterology & Hepatology
Lyell McEwin Hospital
Haydwon Road
Elizabeth Vale
South Australia 5112
Australia
Country
Australia
Secondary sponsor category [1] 299845 0
Individual
Name [1] 299845 0
Prof Rajvinder Singh
Address [1] 299845 0
Department of Gastroenterology & Hepatology
Lyell McEwin Hospital
Haydown Road
Elizabeth Vale
South Australia 5112
Australia
Country [1] 299845 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301200 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [1] 301200 0
Ethics committee country [1] 301200 0
Australia
Date submitted for ethics approval [1] 301200 0
11/02/2018
Approval date [1] 301200 0
12/04/2018
Ethics approval number [1] 301200 0
Q20170308

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 86202 0
Dr Damian Harding
Address 86202 0
Department of Gastroenterology & Hepatology
Lyell McEwin Hospital
Haydown Road
Elizabeth Vale
South Australia 5112
Country 86202 0
Australia
Phone 86202 0
+61 (08) 8282 1897
Fax 86202 0
Email 86202 0
[email protected]
Contact person for public queries
Name 86203 0
Damian Harding
Address 86203 0
Department of Gastroenterology & Hepatology
Lyell McEwin Hospital
Haydown Road
Elizabeth Vale
South Australia 5112
Country 86203 0
Australia
Phone 86203 0
+61 (08) 8282 1897
Fax 86203 0
Email 86203 0
[email protected]
Contact person for scientific queries
Name 86204 0
Damian Harding
Address 86204 0
Department of Gastroenterology & Hepatology
Lyell McEwin Hospital
Haydown Road
Elizabeth Vale
South Australia 5112
Country 86204 0
Australia
Phone 86204 0
+61 (08) 8282 1897
Fax 86204 0
Email 86204 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?
De-identified data (includes subject gender, age, liver status, metabolic data, physical findings) obtained at baseline and at the completion of the study.
When will data be available (start and end dates)?
Individual participant data for this trial will be available at completion of the study (when week 48 data are complete for all recruited subjects), and until 2 years after the completion of the study.
Available to whom?
Case-by-case basis at the discretion of the principal investigator.
Available for what types of analyses?
To achieve the aims of the study.
How or where can data be obtained?
Access subject to approval of the principal investigator.


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.