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Trial registered on ANZCTR


Registration number
ACTRN12616000710426
Ethics application status
Approved
Date submitted
24/05/2016
Date registered
30/05/2016
Date last updated
18/01/2019
Date data sharing statement initially provided
18/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
The effects of exenatide extended release ( Bydureon) on appetite and gastric emptying in Prader-Willi syndrome
Scientific title
The effects of a exenatide extended release ( Bydureon) on appetite and gastric emptying in Prader-Willi syndrome
Secondary ID [1] 289245 0
Nil known
Universal Trial Number (UTN)
Trial acronym
ENGAGE PWS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prader-Willi syndrome 298820 0
Condition category
Condition code
Metabolic and Endocrine 298876 298876 0 0
Other endocrine disorders
Human Genetics and Inherited Disorders 298878 298878 0 0
Other human genetics and inherited disorders
Neurological 298966 298966 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Administration of exenatide extended realease ( Bydureon) 2mg subcutaneous injection once weekly on adults with Prader-Willi Syndrome for 12 weeks. Adherence will be monitored by return of empty or unused injection pens by the patients or carers of patients.

Gastric emptying assessment is performed using the gold standard gastric scintigraphy.
Participants will fast from 10:00pm the night before the study. On the day of the study, anthropometric measurements will be taken and fasting blood samples will be drawn. In St Vincent Hospital’s nuclear medicine unit, a cannula will be placed in participants’ arms and they will be given a meal (scrambled eggs with potato, ricotta and cheese) labelled with 99mTc Calcium Phytate Colloid and asked to eat it within 10 minutes. Participants will then lie supine during four 10-minute scans: immediately after eating the meal and at 1 hour, 2 hours and 4 hours postprandial. Blood samples will be collected prior to meal ingestion and immediately before each scanning time point. Plasma and serum will be obtained from blood samples collected during the study by centrifugation and stored at -80°C until being analysed for levels of glucose, insulin, gut hormones and lipids. Appetite will be assessed using hunger and fullness visual analogue scales before and hourly after the meal. After completion of the scintigraphy study, participants will have a DXA scan to quantify lean mass and fat mass.
Intervention code [1] 294785 0
Treatment: Drugs
Comparator / control treatment
Lean and obese healthy control groups will be enrolled to compare baseline gastric emptying, anthropometric characteristics, appetite scores, cognitive function scores , and circulating levels of hormones, lipids and cytokines between groups to determine differences between the PWS group and the lean and obese control groups. .
The control groups will not receive exenatide treatment.
Control group
Active

Outcomes
Primary outcome [1] 298351 0
To determine the gastrointestinal safety of exenatide extended release (Bydureon) treatment in PWS by assessing its effects on gastric emptying using gold standard gastric scintigraphy.
Timepoint [1] 298351 0
Week 0,4 and 12 of post commencement of treatment with exenatide extended release ( Bydureon)
Primary outcome [2] 298352 0
To assess appetite using Visual Analogue Scale for hunger and fullness ( validated in PWS) in the following comparisons:
a) between groups at baseline and
b) between baseline and post commencement of treatment of weekly exenatide ( Bydureon) in PWS group
Timepoint [2] 298352 0
a) at week 0 before commencement of treatment
b)at baseline ,week 4 and 12 post commencement of treatment with exenatide extended release ( Bydureon)
Primary outcome [3] 298433 0
To assess body weight using digital weighing scales in the following comparisons:
a) between groups at baseline and
b) between baseline and post commencement of treatment of weekly exenatide ( Bydureon) in PWS group
Timepoint [3] 298433 0
a) at week 0 before commencement of treatment
b)at baseline ,week 4 and 12 post commencement of treatment with exenatide extended release ( Bydureon)
Secondary outcome [1] 323919 0
To assess gastric emptying rate at baseline in adults with PWS compared to lean and obese control subjects using gastric emptying scintigraphy.
Timepoint [1] 323919 0
Week 0 before commencement of treatment
Secondary outcome [2] 324117 0
To assess the effects of weekly administration of weekly exenatide ( Bydureon) on behaviour using the Hyperphagia Questionnaire ( validated in PWS) in PWS group
Timepoint [2] 324117 0
0, 4 and 12 weeks post commencement of treatment with exenatide extended release ( Bydureon)
Secondary outcome [3] 324118 0
To assess cognitive function using three tablet-based games (Cambridge Neuropsychological Automated Testing Battery (CANTAB) software, Cambridge, UK) in the following comparisons:
a) between groups at baseline and
b) between baseline and post commencement of treatment of weekly exenatide ( Bydureon) in PWS group
Timepoint [3] 324118 0
a) at week 0 before commencement of treatment
b)at baseline ,week 4 and 12 post commencement of treatment with exenatide extended release ( Bydureon)
Secondary outcome [4] 324119 0
To assess anthropometric characteristics (height, weight, waist/hip circumference) in the following comparisons:
a)between groups at baseline and
b) between baseline and post commencement of treatment of weekly exenatide (Bydureon) in PWS group
This is a composite secondary outcome.
Anthropometric characteristics (height, weight, waist/hip circumference) will be asessed with the following method:
a)height- using wall mounted stadiometer
b)weight-using digital weighing scales
c)waist/hip circumference- using tape measure
Timepoint [4] 324119 0
a) at week 0 before commencement of treatment
b)at baseline ,week 4 and 12 post commencement of treatment with exenatide extended release ( Bydureon)
This is a composite secondary outcome.
Secondary outcome [5] 324121 0
To assess circulating factors ( hormones) using immunoassay in the following comparisons:
a)between groups at baseline and
b) between baseline and post commencement of treatment of weekly exenatide ( Bydureon) in PWS group
Timepoint [5] 324121 0
a) at week 0 before commencement of treatment
b)at baseline ,week 4 and 12 post commencement of treatment with exenatide extended release ( Bydureon)
Secondary outcome [6] 324227 0
To assess circulating factors ( lipids) using colorimetric assay in the following comparisons:
a)between groups at baseline and
b) between baseline and post commencement of treatment of weekly exenatide ( Bydureon) in PWS group
Timepoint [6] 324227 0
a) at week 0 before commencement of treatment
b)at baseline ,week 4 and 12 post commencement of treatment with exenatide extended release ( Bydureon)
Secondary outcome [7] 324228 0
To assess circulating factors ( cytokines) using immunoassay in the following comparisons:
a)between groups at baseline and
b) between baseline and post commencement of treatment of weekly exenatide ( Bydureon) in PWS group
Timepoint [7] 324228 0
a) at week 0 before commencement of treatment
b)at baseline ,week 4 and 12 post commencement of treatment with exenatide extended release ( Bydureon)
Secondary outcome [8] 365901 0
To assess composite outcome of arterial stiffness and heart rate variability a) between groups at baseline and b)between baseline and post commencement of treatment of weekly exenatide ( Bydureon) in PWS group using a Sphygmocor Device and by 3-lead ECG for 10 minutes.
Timepoint [8] 365901 0
a) at week 0 before commencement of treatment b)at baseline ,week 4 and 12 post commencement of treatment with exenatide extended release ( Bydureon)
Secondary outcome [9] 365902 0
Side effects of Bydureon will be monitored closely by the study investigators throughout the study period. Possible side effects include nausea vomiting, diarrhoea, constipation and low blood sugar levels. These symptoms are unlikely to occur; if experienced, they are usually not harmful. Investigators are constantly in contact with participants via email and phone and will be notified of any symptoms that the participants experience by the parents, carers or healthcare provider.
Timepoint [9] 365902 0
Throughout the study period once commencement of treatment
Secondary outcome [10] 365903 0
Plasma and serum will be obtained from blood samples collected during the study by centrifugation and stored at -80°C until being analysed for levels of IGF-1, 25 O,H Vitamin D and HbA1c . This is a composite secondary outcome as Vitamin D and Insulin-like growth factor ( IGF-1) concentrations may be related.
Timepoint [10] 365903 0
At baseline before commencement of treatment.
Secondary outcome [11] 365904 0
Assessment of behaviour using a behavioural questionnaire using the Hyperphagia Questionnaire validated for use in PWS.
Timepoint [11] 365904 0
Assessed at baseline before commencement of treatment, at week 4 and week 12 of treatment
Secondary outcome [12] 365905 0
Assessment of cognition using a validated three tablet-based games will be performed. The CANTAB Cambridge Cognition software has been validated to use in those with cognitive impairment.
Timepoint [12] 365905 0
Assessed at baseline before commencement of treatment, at week 4 and week 12 of treatment

Eligibility
Key inclusion criteria
PWS group: genetic diagnosis of PWS
BMI-matched group( instead of Obese group): healthy; any obesity-related comorbidities must be treated, BMI -matched to PWS cohort.
Lean group: health; BMI <25
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
PWS: Uncontrolled access to food in current living situation; history of psychological illness within previous 12 months; pregnant women.
Obese: unstable body weight within previous 3 months (+/- 2kg or greater); pregnant women.
Lean: unstable body weight within previous 3 months (+/- 2kg or greater); pregnant women.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
For baseline gastric emptying, anthropometric characteristics, appetite scores, cognitive function scores , and circulating levels of hormones, lipids and cytokines, we will perform between-group comparisons to determine differences between the PWS group and the lean and obese control groups.

Treatment effects on gastric emptying, anthropometric characteristics, appetite scores, cognitive function scores , food-related behavioural assessment scores and circulating levels of hormones, lipids and cytokines will be assessed in the PWS group at 4 weeks and 12 weeks post-treatment compared to baseline. Multiple linear regression will be used to determine factors that predict treatment effects on endpoints.

To detect a difference in 4-hour gastric retention between groups with statistical power 1- beta>0.85, we will require 8 individuals in each group. Allowing for a drop-out rate of 20%, this requires 10 participants for each of the control groups. As we anticipate that some PWS participants may not be eligible to enter the treatment arm of the study, we aim to recruit 20 individuals in the PWS group initially.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
20/06/2016
Actual
8/12/2016
Date of last participant enrolment
Anticipated
30/09/2019
Actual
Date of last data collection
Anticipated
28/12/2019
Actual
Sample size
Target
40
Accrual to date
28
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 293624 0
Charities/Societies/Foundations
Name [1] 293624 0
Garvan Foundation
Country [1] 293624 0
Australia
Primary sponsor type
Other
Name
Garvan Institute of Medical Research
Address
384 Victoria Street
Darlinghurst NSW 2010
Country
Australia
Secondary sponsor category [1] 292477 0
None
Name [1] 292477 0
N/A
Address [1] 292477 0
N/A
Country [1] 292477 0
Other collaborator category [1] 279001 0
Hospital
Name [1] 279001 0
St Vincent's Hospital
Address [1] 279001 0
390 Victoria Street
Darlinghurst NSW 2010
Country [1] 279001 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295062 0
St Vincent's Hospital Human Research Ethics Committee
Ethics committee address [1] 295062 0
Level 6, de Lacy Building
St Vincent’s Hospital
390 Victoria Street
Darlinghurst NSW 2010
Ethics committee country [1] 295062 0
Australia
Date submitted for ethics approval [1] 295062 0
01/11/2015
Approval date [1] 295062 0
03/05/2016
Ethics approval number [1] 295062 0

Summary
Brief summary
Prader-Willi syndrome (PWS) is a rare genetic disorder that causes individuals with the
disease to have an insatiable appetite, which often leads to the development of morbid obesity. The only way that this appetite can be controlled is through constant vigilance, behavioural restraints and environmental modifications; there is currently no pharmacological treatment for excessive appetite in PWS.
A single injection of exenatide, a GLP-1 hormone agonist, has been shown to increase feelings of fullness after a meal in adults with PWS. The effects of the long term administration of a GLP-1 agonist on appetite and weight management in PWS, however, have not been studied. The proposed study aims to redress this by assessing changes in gastric emptying rate, fullness, hunger, food-related behaviours, appetite hormones, cognitive function and body weight in a cohort of 20 adults with PWS treated for 12 weeks with the GLP-1 agonist Bydureon.
Study participants will undergo a meal study prior to beginning Bydureon treatment to assess their response of hormones and appetite to food intake. As there have been some studies demonstrating that Bydureon slows gastric emptying, participants’ gastric emptying rate will be also be assessed by scintigraphy so that changes in gastric motility can be monitored for tolerance, with a normal gastric emptying range established from 10 lean control individuals and 10 obese control individuals. If PWS particpants’ gastric emptying rate falls within the normal range, they will begin a 12-week Bydureon treatment period with weekly injections of the drug.
After 4 weeks of Bydureon treatment, gastric emptying rate will be measured again. If it has slowed below the normal range, treatment will be discontinued. Otherwise, treatment will be continued up to 12 weeks, after which PWS participants will undergo a further meal/scintigraphy study to determine the effect that Bydureon treatment has had on appetite, weight, behaviour and cognitive function. Body weight will be measured again 12 weeks after completion of the treatment period.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 886 886 0 0
/AnzctrAttachments/370723-ENGAGE_Protocol_v2.docx
Attachments [2] 887 887 0 0
/AnzctrAttachments/370723-Letter - HREC FINAL approval at HREC Exec meeting 02 05 2016 OOS - 15 291 (1).pdf
Attachments [3] 888 888 0 0
/AnzctrAttachments/370723-ENGAGE_PICF_PersonResponsible_v4.pdf
Attachments [4] 889 889 0 0
/AnzctrAttachments/370723-ENGAGE_PICF_Self_v4.pdf
Attachments [5] 895 895 0 0
/AnzctrAttachments/370723-Scintigraphy protocol.pdf
Attachments [6] 896 896 0 0
/AnzctrAttachments/370723-Bydureon_Consumer_Information.pdf
Attachments [7] 897 897 0 0
/AnzctrAttachments/370723-Bydureon_Product_Information.pdf

Contacts
Principal investigator
Name 65950 0
A/Prof Alexander Viardot
Address 65950 0
Garvan Institute of Medical Research
384 Victoria Street,
Darlinghurst NSW 2010
Country 65950 0
Australia
Phone 65950 0
+61283822622
Fax 65950 0
Email 65950 0
a.viardot@garvan.org.au
Contact person for public queries
Name 65951 0
Alexander Viardot
Address 65951 0
Garvan Institute of Medical Research
384 Victoria Street,
Darlinghurst, NSW 2010
Country 65951 0
Australia
Phone 65951 0
+61283822622
Fax 65951 0
Email 65951 0
a.viardot@garvan.org.au
Contact person for scientific queries
Name 65952 0
Alexander Viardot
Address 65952 0
Garvan Institute of Medical Research
384 Victoria Street
Darlinghurst NSW 2010
Country 65952 0
Australia
Phone 65952 0
+61283822622
Fax 65952 0
Email 65952 0
a.viardot@garvan.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The study is not a sponsored study so all data is purely for scientific use without any commercial involvement.


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.