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Trial registered on ANZCTR


Trial ID
ACTRN12613001069741
Ethics application status
Approved
Date submitted
23/09/2013
Date registered
24/09/2013
Date last updated
27/08/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
The combined effect of Liraglutide and Sleeve Gastrectomy on Metabolic, Cardiac, Neurological and Sleep Function in Obese Diabetes: A Twelve-Month Randomised Study.
Scientific title
The combined effect of Liraglutide and Sleeve Gastrectomy on Metabolic, Cardiac, Neurological and Sleep Function in Obese Individuals with Type 2 Diabetes Mellitus: A Twelve-Month, Randomised, Parallel-Group, Placebo-Controlled Study.
Secondary ID [1] 283286 0
Nil
Universal Trial Number (UTN)
U1111-1137-7794
Trial acronym
LIRASLEEVE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 Diabetes Mellitus 290168 0
Obesity 290169 0
Condition category
Condition code
Metabolic and Endocrine 290555 290555 0 0
Diabetes
Diet and Nutrition 290560 290560 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients who have elected to have bariatric surgery or medical management for weight loss will be randomised to receive 1.8mg liraglutide daily, administered subcutaneously, for 12 months. Participants will commence liraglutide/placebo treatment within 2 weeks of bariatric surgery taking place or starting medical management for obesity.
Participants will be asked to return any unused study drug at each study visit; this will be used as a way to monitor adherence to the study medication protocol. Furthermore, fasting blood glucose will be measured at each study visit, as a way of monitoring glycaemic control in the study participants.
Intervention code [1] 288011 0
Treatment: Drugs
Comparator / control treatment
Placebo, containing the same constituents and excipients as the liraglutide pen injector, apart from the active component (liraglutide).
Control group
Placebo

Outcomes
Primary outcome [1] 290578 0
The change in body weight, as assessed by standard anthropometric measures, such as weight, height, waist circumference, BMI calculation and body composition (evaluated by dual x-ray absorptiometry).
Timepoint [1] 290578 0
12 months
Secondary outcome [1] 304827 0
Change in metabolic variables, including glycaemic control, which will be determined by glycosylated HbA1c, fasting plasma glucose, fasting insulin, number of patients taking insulin compared to baseline, insulin dose and medication usage.
Timepoint [1] 304827 0
12 months
Secondary outcome [2] 304828 0
Change in cardiac function, determined by change in clinical cardiac endpoints such as heart rate and blood pressure. Cardiac magnetic resonance will be used to measure left ventricular mass, left ventricular mass index, left ventricular ejection fraction, left ventricular diastolic function, left atrial size, right ventricular function and aortic function-distensibility. Echocardiography will be used to measure left ventricular ejection fraction and left ventricular diastolic function.
Timepoint [2] 304828 0
12 months
Secondary outcome [3] 304829 0
The change in neural and neurocognitive function, assessed by MRI brain and the IntegNeuro cognitive assessment tool.
Timepoint [3] 304829 0
12 months
Secondary outcome [4] 304830 0
Change in sleep function, as measured by the Epworth Sleepiness Scale, and overnight polysomnography, from which the apnoea-hypopnoea index will be calculated.
Timepoint [4] 304830 0
12 months

Eligibility
Key inclusion criteria
- Subjects diagnosed with type 2 diabetes mellitus who have elected to undergo bariatric surgery or medical management for weight loss
- Body mass index greater than 35kg/m2 or 30kg/m2 with at least 2 medical co-morbidities
- Body weight less than 150kg; waist circumference less than 150cm
- HbA1c: 7%-10% (both inclusive) in subjects on anti-diabetes combination therapy
- HbA1c: 7%-11% (both inclusive) in subjects on anti-diabetes monotherapy
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Impaired liver function, defined as alanine aminotransferase (ALT) greater than or equal to 3 times the upper limit of normal (one retest within one week is permitted with the results from the last sample being conclusive)
- Impaired renal function, defined as serum-creatinine greater than or equal to 135umol/l for males and 110umol/l for females (one retest within one week is permitted with the results from the last sample being conclusive)
- Clinically significant active cardiovascular disease including history of myocardial infarction within the past 6 months and/or heart failure (New York Heart Association (NYHA) class III and IV) at the discretion of the Investigator
- Proliferative retinopathy or maculopathy requiring acute treatment as judged by the Investigator
- Recurrent major hypoglycaemia as judged by the Investigator
- Use of any drug (except for anti-diabetes medication), which in the Investigator's opinion could interfere with the glucose level (e.g. systemic corticosteroids)
- Pregnancy or lactation
- History of pancreatitis or pancreatic cancer
- Patients with a past history of GLP-1 analogue associated pancreatitis
- History of medullary thyroid cancer
- Contraindications to liraglutide or any of its excipients
- Hypersensitivity to liraglutide or similar drugs
- Suspected or known abuse of alcohol or narcotics

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)
Participants will be screened and recruited to the study at visit 1 (-6 weeks before administration of study drug/placebo). Subsequently, participants will be randomised to treatment (liraglutide or placebo) at visit 3 (-1 weeks before administration of study drug/placebo). In order to avoid bias, both researchers and participants will be blind to the treatment group allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation list will be created by the allocation study nurse using a Microsoft Excel spreadsheet, in consultation with The George Institute for Global Health, Australia. Block randomisation will be used, such that balance across the treatment groups is achieved. On site randomisation will be carried out by an un-blinded study nurse, who will ensure allocation of participants to the correct treatment group. A study independent advisor from The George Institute will oversee the randomisation process.
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 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Based on previous studies, which have determined the effect of liraglutide on weight loss, we have determined that with a sample size of 120, we will be able to detect a weight difference of 5.1kg, with 80% power and a significance level of 0.05. Furthermore, we will be powered (80%) to detect a difference in fat mass of 1kg by DXA scanning, with a significance level of 0.05.
Statistical analysis will be performed using SPSS version 19 (SPSS Inc., Chicago, Illinois). The George Institute will assist with statistical analysis of results obtained throughout the study. Statistical methods to be used will include analysis of covariance, logistic regression models and survival analyses. Specific statistical tests will include student's t-test, Mann-Whitney U test, and Wilcoxon rank tests. All data will be analysed using the intention-to-treat principle.

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)
NSW
Recruitment hospital [1] 1537 0
Royal North Shore Hospital - St Leonards
Recruitment postcode(s) [1] 7376 0
2065 - Royal North Shore Hospital

Funding & Sponsors
Funding source category [1] 288026 0
Commercial sector/Industry
Name [1] 288026 0
Novo Nordisk
Address [1] 288026 0
Level 3
21 Solent Circuit
BAULKHAM HILLS NSW 2153
AUSTRALIA
Country [1] 288026 0
Australia
Primary sponsor type
Hospital
Name
Northern Sydney Local Health District
Address
Royal North Shore Hospital
Reserve Road, St Leonards,
NSW 2065
Country
Australia
Secondary sponsor category [1] 286742 0
None
Name [1] 286742 0
Address [1] 286742 0
Country [1] 286742 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289947 0
Northern Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 289947 0
Research Office,
Level 13, Kolling Institute,
Reserve Road,
Royal North Shore Hospital
St Leonards,
NSW 2065
Ethics committee country [1] 289947 0
Date submitted for ethics approval [1] 289947 0
Approval date [1] 289947 0
09/07/2013
Ethics approval number [1] 289947 0
1211-383M

Summary
Brief summary
This project will examine the effect of weight loss induced by the administration of the GLP-1 analogue, liraglutide, in combination with bariatric surgery or medical management on factors associated with metabolic and end-organ abnormalities. It is likely that liraglutide will improve the metabolic and neurohormonal profile of patients with obesity. Complications of obesity including cardiac pathology, neurocognitive dysfunction and sleep-disordered breathing may improve as a result of weight loss, with the use of a GLP-1 analogue.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 43218 0
Prof Greg Fulcher
Address 43218 0
Department of Diabetes, Endocrinology and Metabolism,
Level 3, Acute Services Building,
Royal North Shore Hospital,
Reserve Road,
St Leonards,
NSW 2065
Country 43218 0
Australia
Phone 43218 0
+61294631680
Fax 43218 0
Email 43218 0
greg.fulcher@sydney.edu.au
Contact person for public queries
Name 43219 0
Dr Rachel McGrath
Address 43219 0
Department of Diabetes, Endocrinology and Metabolism,
Level 3, Acute Services Building,
Royal North Shore Hospital,
Reserve Road,
St Leonards,
NSW 2065
Country 43219 0
Australia
Phone 43219 0
+61294631470
Fax 43219 0
Email 43219 0
Rachel.McGrath@health.nsw.gov.au
Contact person for scientific queries
Name 43220 0
Dr Rachel McGrath
Address 43220 0
Department of Diabetes, Endocrinology and Metabolism,
Level 3, Acute Services Building,
Royal North Shore Hospital,
Reserve Road,
St Leonards,
NSW 2065
Country 43220 0
Australia
Phone 43220 0
+61294631470
Fax 43220 0
Email 43220 0
Rachel.McGrath@health.nsw.gov.au