Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615001229561
Ethics application status
Approved
Date submitted
4/11/2015
Date registered
10/11/2015
Date last updated
18/12/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Effects and Mechanisms of Action of an Endoscopically Placed Duodenal-Jejunal Sleeve Device (Endobarrier) in Obese Patients with Type II Diabetes
Scientific title
Effects of Immediate Endobarrier Insertion on Weight Loss and Glycaemic Control Compared with Standard Nutritional Care and Delayed Endobarrier Insertion in Patients with Type II Diabetes
Secondary ID [1] 287734 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 Diabetes Mellitus 296582 0
Obesity 296583 0
Condition category
Condition code
Metabolic and Endocrine 296835 296835 0 0
Diabetes
Diet and Nutrition 296836 296836 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
40 patients will be recruited for this study. All patients will have an Endobarrier device inserted. Endobarrier insertion occurs endoscopically by trained endoscopists and is fluoroscopically assisted for delivery to just below the pyloric sphincter where the device will settle and attach to the mucosa. The procedure takes approximately 45 minutes.

Following recruitment the patients will be randomised to either have an Endobarrier device inserted immediately (20 patients-Group “ETG-0”) or to be treated with standard, conservative weight loss management. Those that did not immediately have a device inserted will be randomised again after 6 months. Half of these patients will then have a device inserted immediately (10 patients-Group “ETG-6”) or continue with standard conservative management for a total of 12 months before the device is inserted (10 patients- Group “ETG-12”) . The Endobarrier device will be removed after a maximum insertion period of 12 months.
Intervention code [1] 293129 0
Treatment: Devices
Comparator / control treatment
50% of participants receive standard nutritional care for 6- 12 months prior to device insertion. Standard nutritional care involves patients being seen at 3 monthly intervals by the Accredited Practicing Dietitian for the trial for 1 hour indvidualised dietary advice for dietary modification to improve diet quality and promote weight loss (calorie control).
Control group
Active

Outcomes
Primary outcome [1] 296446 0
Weight loss - assessed via weight on digital scales at each appointment.
Timepoint [1] 296446 0
Measured at initial appointment, baseline (device insertion), 1 month, 2 months, 6 months, 12 months and 24 months.

For the delayed insertion group, weight will be measured 3-monthly prior to insertion and then as above.
Secondary outcome [1] 318462 0
Quality of life as measured by the SF-36 v2
Timepoint [1] 318462 0
Measured at initial visit, 6 months, 12 months and 24 months
Secondary outcome [2] 318463 0
Liver function - measured via blood tests measuring liver fibrosis markers e.g. hyaluronic acid and a liver function panel including GGT, AST, ALT.

Liver function will also be assessed by fibroscan to determine fibrosis
Timepoint [2] 318463 0
Blood panels conducted at initial appointment, baseline (device insertion), 1 month, 2 months, 6 months, 12 months and 24 months.

Fibroscan conducted at initial visit,2 months, 6 months, 12 months and 24 months
Secondary outcome [3] 318464 0
Psychological wellbeing measured using hospital anxiety and depression scale
Timepoint [3] 318464 0
Measured at initial visit, 6 months, 12 months and 24 months
Secondary outcome [4] 318465 0
Intraluminal digestion of triglycerides measure by a 13C labeled mixed triglyceride breath test
Timepoint [4] 318465 0
Measured at initial visit, 1 months, 12 months and 24 months
Secondary outcome [5] 318466 0
fasting insulin measured via blood assay
Timepoint [5] 318466 0
Blood panels conducted at initial appointment, baseline (device insertion), 1 month, 2 months, 6 months, 12 months and 24 months.
Secondary outcome [6] 318467 0
mucosal microbiome - Community profiling will enable characterisation of the bacterial diversity of the gastric and duodenal mucosa-associated microbiome. Microbial DNA extractions from snap-frozen samples will be undertaken using previously established methods. Extracted DNA will be amplified using barcoded primer sets that target one of the hypervariable regions of the gene encoding 16S ribosomal RNA (rRNA). Sequencing of these PCR products will allow identification of microbes to a genus/species level.
Timepoint [6] 318467 0
Baseline versus device removal (12 months of device dwelling)
Secondary outcome [7] 318468 0
Cardiopulmonary reserve and exercise capacity measured by a 6 minute walk test - composite outcome
Timepoint [7] 318468 0
Measured at initial visit, 6 months, 12 months and 24 months
Secondary outcome [8] 318662 0
Fasting blood glucose measured by blood assay
Timepoint [8] 318662 0
Blood panels conducted at initial appointment, baseline (device insertion), 1 month, 2 months, 6 months, 12 months and 24 months.
Secondary outcome [9] 318663 0
Stool microbiome - Community profiling will enable characterisation of the bacterial diversity of the gastric and duodenal mucosa-associated microbiome. Microbial DNA extractions from snap-frozen samples will be undertaken using previously established methods. Extracted DNA will be amplified using barcoded primer sets that target one of the hypervariable regions of the gene encoding 16S ribosomal RNA (rRNA). Sequencing of these PCR products will allow identification of microbes to a genus/species level.
Timepoint [9] 318663 0
Baseline vs device removal (12 months of device dwelling)

Eligibility
Key inclusion criteria
1. Aged between 18 and 65 years.
2. Functional level equivalent to an ECOG score of 2 or less.
3. Obese – BMI over 35.
4. Type II diabetes mellitus on oral hypoglycaemic agents but not insulin.
5. English speaking.
6. Willing to participate in a 3 year trial and with capacity to consent.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria prior to recruitment will include:
1. Prior gastric or intestinal surgery including (not exclusively) the following:
a. Nissen Fundoplication, gastrectomy,
b. Vertical Banded Gastroplasty, Gastric Bypass, gastric partitioning, gastric stapling, gastric resection, placement of the LAPBAND (Trademark) System,
c. Small bowel resection, colon resection, colostomy,
d. Gynaecological surgery.
2. Any inflammatory disease of the gastrointestinal tract including oesophagitis, gastric ulceration, duodenal ulceration, cancer or specific inflammation such as Crohn’s disease.
3. Potential upper gastrointestinal bleeding conditions such as oesophageal or gastric varices, congenital or acquired intestinal telangiectasis, or other congenital anomalies of the gastrointestinal tract such as atresias or stenoses.
4. A large hiatal hernia.
5. A structural abnormality in the oesophagus or pharynx such as a stricture or diverticulum.
6. Significant coronary artery disease. (Previous myocardial infarction or angina in the past 90 days.)
7. Any medical condition that requires or is likely to require anticoagulation or dual anti-platelet therapy during the study period.
8. Any condition that requires the patient to take non-steroidal anti-inflammatory drugs during the study period.
9. Any active malignancy.
10. Any medical condition with a likely survival of 5 years or less.
11. Any patient likely to require abdominal surgery during the study period.
12. Patient or family history of connective tissue disease.
13. Known upper gastrointestinal abnormality.
14. Pregnancy.
15. Known chronic pancreatitis.
16. Poor functional status ECOG greater than or equal to 3.
17. Antibiotic use at the time of endoscopy.
18. Any other medical condition which would not permit elective endoscopy.
19. Major prior or present psychological disorder including alcoholism or drug addiction.

Exclusion criteria after recruitment will include:
1. Inadequate cardiopulmonary reserve for anaesthetisation.
2. Structural or mucosal abnormality found during upper endoscopy that would preclude implantation.
3. Withdrawal of consent.
4. Clinician concern regarding any of the above exclusion criteria.

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)
A treating investigator will open an envelope corresponding to the patient’s sex and determine their treatment number. This number will correspond to a randomly generated list of numbers and its corresponding group allocation, (A or B.) This process will be repeated for group B with a repeated randomisation at 6 months for those without a device inserted. At this time a stratified (correcting for sex) block randomisation into 2 equal groups will occur using the same envelope method.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Eligible patients will be randomised into two groups (A and B) according to a stratified block randomisation scheme. Stratification will be based on sex as this is likely to be an important variable that should be corrected for to achieve treatment balance. This ensures that the cumulative number of assignments to each treatment arm will be balanced. Two groups of sealed envelopes divided by sex will contain the numbers 1 to 20.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Stepped-wedge design
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample size calculations were not performed as this is a pilot trial and number was selected based on maximal resource allowance.

Data will be statistically analysed in-house by adequately trained staff.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
Cancellation of Endobarrier listing on ARTG
Date of first participant enrolment
Anticipated
16/11/2015
Actual
1/02/2016
Date of last participant enrolment
Anticipated
Actual
1/07/2016
Date of last data collection
Anticipated
30/06/2018
Actual
Sample size
Target
40
Accrual to date
Final
15
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 4507 0
Princess Alexandra Hospital - Woolloongabba

Funding & Sponsors
Funding source category [1] 292277 0
Hospital
Name [1] 292277 0
Princess Alexandra Hospital
Country [1] 292277 0
Australia
Primary sponsor type
Hospital
Name
Princess Alexandra Hospital
Address
199 Ipswich Road
Wooloongabba QLD 4102
Country
Australia
Secondary sponsor category [1] 290963 0
None
Name [1] 290963 0
Address [1] 290963 0
Country [1] 290963 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293753 0
Metro South Human Research Ethics Committee
Ethics committee address [1] 293753 0
PAH Centres for Health Research
Level 7, Translational Research Institute
37 Kent Street
Woolloongabba QLD 4102
Ethics committee country [1] 293753 0
Australia
Date submitted for ethics approval [1] 293753 0
01/05/2015
Approval date [1] 293753 0
08/09/2015
Ethics approval number [1] 293753 0
HREC/15/PAH/246

Summary
Brief summary
The aim of the study is to obtain an understanding of mechanisms of action and the biological and psychosocial effects of an Endoluminal Bariatric Intervention (Endobarrier-DJBS) in an obese diabetic population.

Hypothesis:
Implantation of the Endobarrier device will reduce:
1. Body weight as compared to the baseline values and compared to control interventions,
2. Intraluminal digestion of triglycerides as measures by the 13C triglyceride breath test in patients with EB device as compared to baseline and controls;
3. Fasting insulin and fasting glucose during the intervention and improvement will be greater in actively treated subjects.
In addition the implantation of the Endobarrier device will:
4. Alter the mucosal and stool microbiome,
5. Improve liver function and parameters of fibrosis (elastography, blood tests, liver biopsy ).
6. Improve cardiopulmonary reserve and exercise capacity,
7. Improve quality of life, self-image, anxiety and depression will improve in actively treated subjects as compared to baseline.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 61166 0
Prof Gerald Holtmann
Address 61166 0
Princess Alexandra Hospital
199 Ipswich Road
Wooloongabba
QLD 4102
Country 61166 0
Australia
Phone 61166 0
+61731767792
Fax 61166 0
Email 61166 0
[email protected]
Contact person for public queries
Name 61167 0
Miss Jessica McMaster
Address 61167 0
Princess Alexandra Hospital
199 Ipswich Road
Wooloongabba
QLD 4102
Country 61167 0
Australia
Phone 61167 0
+61731767792
Fax 61167 0
Email 61167 0
[email protected]
Contact person for scientific queries
Name 61168 0
Prof Gerald Holtmann
Address 61168 0
Princess Alexandra Hospital
199 Ipswich Road
Wooloongabba
QLD 4102
Country 61168 0
Australia
Phone 61168 0
+61731767792
Fax 61168 0
Email 61168 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
SourceTitleYear of PublicationDOI
EmbaseInduction of Meal-related Symptoms as a Novel Mechanism of Action of the Duodenal-Jejunal Bypass Sleeve.2020https://dx.doi.org/10.1097/MCG.0000000000001353
N.B. These documents automatically identified may not have been verified by the study sponsor.