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Trial registered on ANZCTR


Registration number
ACTRN12617001613392
Ethics application status
Approved
Date submitted
20/10/2017
Date registered
8/12/2017
Date last updated
5/04/2019
Date data sharing statement initially provided
5/04/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of liraglutide on weight loss in patients with inadequate weight loss following bariatric surgery
Scientific title
Effect of liraglutide on weight loss in patients with inadequate weight loss following bariatric surgery: A Randomised Controlled Trial
Secondary ID [1] 293173 0
Nil
Universal Trial Number (UTN)
U1111-1186-7782
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obesity 305159 0
Failure of adequate weight loss following Laparoscopic Adjustable Gastric Band 305161 0
Condition category
Condition code
Diet and Nutrition 304483 304483 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
48 Patients will be recruited to a double blinded randomised placebo trial whereby patients who have undergone LAGB and achieved a stable, reasonable weight loss (EWL 25-40%; TBWL 5-12%) at 12-18 months post-operation are randomised to liraglutide 3.0 mg or placebo.
Medications will be provided by the manufacturer (Novo Nordisk). In the active treatment arm liraglutide from pre-filled multidose disposable pens (6mg/ml liraglutide, 3ml) will be utilized in the study. Liraglutide and placebo are solutions for injection. The dose of liraglutide utilized in the study will be 3.0mg administered subcutaneously daily from multidose pens. The placebo (control) arm of the study will utilise saline from identical pre-filled multidose disposable pens. Doses of saline will replicate those administered from the active (liraglutide) arm of the study. Each subject will be trained on how to use the multi-dose pen by the trial coordinator and written directions will be provided.
The multi-dose pens will not be disposed we will perform drug accountability and pharmacy reconciliation. Only after drug accountability will pens be sent for destruction.
The trial co-ordinator will assess the amount of trial product returned compared to what was dispensed at the last dispensing visit. Drug/placebo administration will occur daily for the 12 month trial duration, 365 days.
Intervention code [1] 299421 0
Treatment: Drugs
Comparator / control treatment
There will be two arms to this trial with patients being randomised to liraglutide 3.0 mg (active treatment arm) or placebo. The treating practitioner, co-ordinators and patients will be blinded to programme assignment.
Control group
Placebo

Outcomes
Primary outcome [1] 303715 0
The primary endpoint will be the total body weight loss,achieved, measured in %, one year from the commencement of the trial, using clinician assessment and calibrated digital scales.
Timepoint [1] 303715 0
One Year
Secondary outcome [1] 339952 0

o Any complications of the LAGB including, need for re-operation. (band intolerance, slippage or pouch development, erosion, access port leaks, infection and tubing problems).
Band Intolerance, slippage and pouch development.
At the first visit, a barium swallow will be performed to assess the band is in the correct position.
At each monthly visit the patient will be asked if any of the following symptoms have occurred, such as dysphagia, persistent vomiting or any acid reflux which would indicate the formation of a pouch. If there is a pouch, the fluid from the band is removed to allow the oesophagus to recover and the fluid is gradually reintroduced over a period of 1-2 months.
Should a patient have a slippage, this would require a re-operation to correct the position of the band.
An erosion requires the removal of the band
The amount of fluid in the band will be checked and recorded by the physician at the first visit Any indication of a leak in the system, such as marked increase in appetite would initiate a check of the amount of fluid in the system. If there is a leak, the port and tubing are replaced which is a minor operation requiring day surgery only
Any infection would be noted at the clinical examination initially and the at the monthly visits


Timepoint [1] 339952 0
At each clinical visit, at 1,2,3,4,5,6,7,8,9,10,11 and 12 month visit
Secondary outcome [2] 339953 0
Any complications related to treatment (liragluatide 3.0mg or placebo), vomiting, persistent nausea.
These symptoms will be patient reported and treated according to the physicians assessment
.

Timepoint [2] 339953 0
At each clinical visit, 1,2,3,4,5,6,7,8,9,10,11 an 12 month time points
Secondary outcome [3] 340038 0
Change in fasting lipids (total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol), This is a composite measure
Timepoint [3] 340038 0
These tests are at the start visit and the final 12 month visit
Secondary outcome [4] 340039 0
Change in quality of swallowing using a validated questionnaire focusing on quality of swallowing.( Mounes Dakkak, M.R.c.P., and John R. Bennett' M-D. )
J Clinical Gastroenterology 1992; 14(2):99-100
Timepoint [4] 340039 0
These questionnaires will be given at the first visit and at the 12 month visit
Secondary outcome [5] 340040 0
Change in any medication throughout the trial. Patients will be asked to bring all medications with them to each visit
Timepoint [5] 340040 0
This will be checked at each visit. At clinical visits,1, 2, 3, 4, 5, 6, 7, 8 ,9, 10, 11, and 12.
Secondary outcome [6] 340041 0
Rates of follow-up achieved and fail to attend rates
Timepoint [6] 340041 0
These rates will be assessed at each scheduled time point. 1,2,3,4,5,6,7,8,9,10,11,and 12 month
Secondary outcome [7] 340043 0
Drug compliance – comparing the amount of trial product returned to what was dispensed at the last dispensing visit and blood levels of the medication.

Timepoint [7] 340043 0
Patients will be asked to bring all dispensed medication with them to each visit, 1,2,3,4,5,6,7,8,9,10,11 and 12 month time points
Secondary outcome [8] 340165 0
Change in Insulin resistance by serum assay.
Timepoint [8] 340165 0
At the beginning of the trial, then 3, 6 ,9, and 12 month visit
Secondary outcome [9] 340166 0
Change in fasting Glucose by serum assay.
Timepoint [9] 340166 0
At the beginning of the trial, then 3, 6 ,9, and 12 month visit
Secondary outcome [10] 340167 0
Change in C-Peptide by serum assay.
Timepoint [10] 340167 0
At the beginning of the trial, then 3, 6 ,9, and 12 month visit
Secondary outcome [11] 340168 0
Change in Haemaglobin HbA1c by serum assay.
Timepoint [11] 340168 0
At the beginning of the trial, then 3, 6 ,9, and 12 month visit
Secondary outcome [12] 340169 0
Change in Serum Insulin
Timepoint [12] 340169 0
At the beginning of the trial, then 3, 6 ,9, and 12 month visit
Secondary outcome [13] 340170 0
Change in Thyroid function by serum assay.
Timepoint [13] 340170 0
At the beginning of the trial and at the 12 month visit
Secondary outcome [14] 340171 0
Change in Iron studies by serum assay.
Timepoint [14] 340171 0
At the beginning of the trial and at the 12 month visit
Secondary outcome [15] 340172 0
Change in Renal function using urine for micralbuminuria
Timepoint [15] 340172 0
At the beginning of the trial and at the 12 month visit
Secondary outcome [16] 340173 0
Change in High sensitive C-reactive protein by serum assay.
Timepoint [16] 340173 0
At the beginning of the trial and at the 12 month visit
Secondary outcome [17] 340174 0
Change in RBC Folate by serum assay.
Timepoint [17] 340174 0
At the beginning of the trial and at the 12 month visit
Secondary outcome [18] 340175 0
Change in Quality of Life, using Rand 36 item health survey, (SF-36)
Timepoint [18] 340175 0
These questionnaires will be given at the first visit and at the 12 month visit
Secondary outcome [19] 340176 0
Change in any Aspect of health utility using EQ-5D questionnaire.
Timepoint [19] 340176 0
These questionnaires will be given at the first visit and at the 12 month visit
Secondary outcome [20] 340177 0
Any change in mood/depression using Beck Depression Index (BDI)
Timepoint [20] 340177 0
These questionnaires will be given at the first visit and at the 12 month visit
Secondary outcome [21] 340180 0
Surgical complications:

Slipped band

.This would be evident by adverse symptoms such as vomiting and nocturnal reflux. A diagnostic barium meal would be used for assessment. This complication requires a re operation with the band repositioned
Timepoint [21] 340180 0
At each visit ,1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12.

For the 12 month duration of the trial
Secondary outcome [22] 340181 0
Surgical Complication.

Band Erosion.

This would be evident by patient reported symptoms of pain in stomach region. A very rare occurrence. This is diagnosed by gastroscopy. The band would need to be removed in this scenario.
Timepoint [22] 340181 0
At each visit ,1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12.

For the 12 month duration of the trial
Secondary outcome [23] 340182 0
Surgical complication.

Band intolerance.

This is evident when there is persistent vomiting despite all measures taken to alleviate symptoms. This requires removal of the band.
Timepoint [23] 340182 0
At each visit ,1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12.

For the 12 month duration of the trial
Secondary outcome [24] 340183 0
Surgical complications.

Port leaks.

This occurs during a band adjustment when either the port or tubing is accidentally punctured.
This requires a replacement port and tubing involving a day procedure under general anaesthetic.
Timepoint [24] 340183 0
At each visit ,1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12.

For the 12 month duration of the trial
Secondary outcome [25] 340231 0
Change in Vitamin B12 by serum assay
Timepoint [25] 340231 0
At the beginning of the trial and at the 12 month visit.
Secondary outcome [26] 340234 0
Change in Plasma Homocystine by serum assay
Timepoint [26] 340234 0
At the beginning of the trial and at the 12 month visit
Secondary outcome [27] 340235 0
Change in PTH by serum assay
Timepoint [27] 340235 0
At the beginning of the trial and at the 12 month visit

Eligibility
Key inclusion criteria
Patients will be considered for inclusion if they are 12-18 months post LAGB, have achieved a stable weight but have not achieved 12% total body weight loss; are 20-65 years of age. A “Stable Weight” is defined as a weight that is consistent within a 4 kg range over a 3 month period.
Minimum age
20 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients will be excluded from this study if they: have hypersensitivity to liraglutide or any of its excipients; have a past history of GLP-1 analogue associated pancreatitis; will not accept the randomisation process; have a correctable mechanical issue with the LAGB that could explain the lack of weight loss; have a history of previous obesity surgery other than LAGB; have medical issues which contraindicate the application of either arm of the study such as acute myocardial infarction within the past 6 months, dementia, bulimia, active psychosis, concurrent experimental drug use, current pregnancy, lactation, illicit drug use, excessive alcohol intake, use of drugs known to affect body composition, cytotoxic drugs, internal malignancy, or major organ failure; have used a GLP-1 agonist in the previous 12 months; are unable to understand the risks, realistic benefits and compliance requirements of the interventions.
There has been an increase in thyroid cancer reported in rodent models that have utilised liraglutide 3.0 mg and whilst this has not been validated in humans, patients with a personal or family history of medullary thyroid cancer will be excluded. Pancreatitis has been identified as a potential side effect although no studies to date have confirmed this. Because of this concern patient who are at risk of pancreatitis for other reasons (drugs, excessive alcohol intake, known symptomatic gallstones) will be excluded. Nausea is an expected side effect of liraglutide 3.0 mg and it is possible that the gastric band will need to be deflated acutely if the nausea is severe and causes vomiting. Therefore, patients who reside more than one hour from the Clinic will be excluded. Tachycardia is an occasional side effect of liragulatide 3.0 mg with the mechanism currently unknown. Patients with known tachycardia will therefore be excluded. Patients with congestive heart failure NY-HA class III-IV or inflammatory bowel disease will be excluded.

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)
The random assignment of eligible patients will be computer generated by the Monash University School of Public Health and Preventative Medicine (SPHPM) data centre which employs this type of system for all major trials.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by
computer software (i.e. computerised sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis
All data from the study will be managed by the data-centre within CORE. Outcomes will be analysed by an independent biostatistician from the Monash University SPHPM according to intention-to-treat principles. For the primary endpoint, a 95% CI for the difference in group means between groups will be inspected and equivalence will be declared if the ends of the CI both fall within the equivalence margin (-5%, +5%). If necessary, a secondary set of analyses will be performed to adjust for baseline characteristics that are found to be imbalanced between groups where imbalance is pre-specified as a 0.25 standard deviation difference in means (quantitative measures) or an odds ratio of 1.5 (binary measures). Multivariate analysis will be performed using multiple logistic regression for binomial outcomes adjusting for baseline imbalances and potential covariates. Data analysis will be completed by an independent statistician who will be blinded to the allocation of groups. We will analyze by Intent to Treat, Last Observation Carried Forwards (ITT LOCF), Observed case and by Completer analysis, to give estimates of the effect size based on each of these scenarios.


Recruitment
Recruitment status
Recruiting
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
Recruitment hospital [1] 9215 0
The Avenue Private Hospital - Windsor
Recruitment postcode(s) [1] 17870 0
3181 - Windsor

Funding & Sponsors
Funding source category [1] 297799 0
Commercial sector/Industry
Name [1] 297799 0
Novo Nordisk
Address [1] 297799 0
Novo Nordisk Pharmaceuticals Pty. Ltd.
PO Box 7586
Baulkham Hills Business Centre NSW 2153
Australia
Country [1] 297799 0
Australia
Primary sponsor type
University
Name
Monash University
Address
Professor Wendy A Brown
Chair, Department of Surgery
Monash University
The Alfred Centre
99 Commercial Road
Melbourne VIC 3004
Country
Australia
Secondary sponsor category [1] 296863 0
Individual
Name [1] 296863 0
Professor Michael Cowley
Address [1] 296863 0
Michael Cowley, PhD FTSE

Professor, Department of Physiology, Building 13F, Clayton,
Director, Monash Obesity & Diabetes Institute,
Monash University, Victoria, 3800,
Country [1] 296863 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298857 0
The Avenue Hospital
Ethics committee address [1] 298857 0
40 The Avenue, Windsor VIC 3181
Ethics committee country [1] 298857 0
Australia
Date submitted for ethics approval [1] 298857 0
27/06/2017
Approval date [1] 298857 0
16/07/2017
Ethics approval number [1] 298857 0
230

Summary
Brief summary
This research project is testing whether a medication called Saxenda (also known as Liraglutide) can help you lose more weight. Saxenda is approved for use as a weight loss therapy in Australia because it has been shown in obese people to cause weight loss after one year of between 5% and 10% body weight.
We hypothesize pharmacotherapies can be used to improve weight loss following LAGB
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 78462 0
Prof Wendy Brown
Address 78462 0
Monash University
The Alfred Centre
99 Commercial Road
Melbourne VIC 3004
Country 78462 0
Australia
Phone 78462 0
+61 3 9903 0725
Fax 78462 0
+61 3 99030717
Email 78462 0
Wendy.Brown@monash.edu
Contact person for public queries
Name 78463 0
A/Prof John Wentworth
Address 78463 0
A/Prof John Wentworth
Staff Endocrinologist Royal Melbourne Hospital Department of Medicine
Senior Research Officer Walter and Eliza Hall Institute
300 Grattan St, Parkville VIC 3050
Country 78463 0
Australia
Phone 78463 0
+61 422992891
Fax 78463 0
+61 3 93470852
Email 78463 0
wentworth@wehi.edu.au
Contact person for scientific queries
Name 78464 0
Prof Michael Cowley
Address 78464 0
Professor, Department of Physiology, Building 13F, Clayton,
Director, Monash Obesity & Diabetes Institute,
Monash University, Victoria, 3800, Australia
Country 78464 0
Australia
Phone 78464 0
+61 (0) 3 9905 2526
Fax 78464 0
+61 (0) 3 9902 9400
Email 78464 0
michael.cowley@monash.edu

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Participant consent form does not include sharing of individual participant data
What supporting documents are/will be available?
Study protocol
Informed consent form
Ethical approval
Summary results
No Results