Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000141640
Ethics application status
Approved
Date submitted
16/01/2014
Date registered
5/02/2014
Date last updated
3/04/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Investigation of the Impact of Degree of Weight Loss on Physiological Adaptations to Weight Loss
Scientific title
An interventional study investigating if starting BMI or degree of weight loss affect physiological adaptations to weight loss using a VLED (very low energy diet)
Secondary ID [1] 283922 0
nil
Universal Trial Number (UTN)
U1111-1146-9120
Trial acronym
nil
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obesity 290921 0
Condition category
Condition code
Diet and Nutrition 291277 291277 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Very Low Energy Diet (VLED) (OptiFast) for 12 weeks. All participants will be placed on OptiFast for a duration of 12 weeks. The OPTIFAST program is a total food
replacement for the overweight. It is intended for use as part of the management of the moderately to severely overweight persons. The OPTIFAST program has been clinically developed and scientifically formulated to totally replace normal food intake. Weight loss is comparable to that achieved by total fasting whilst minimising the complications of severe ketosis and muscle loss. The OPTIFAST formulation includes high quality protein, sufficient quantities of protein (for nitrogen sparing
and to preserve lean body mass), carbohydrates, fatty acids, and follows the Recommended Dietary Intake (RDI) for vitamins, minerals and trace elements. Fortnightly measurements of urinary ketones will be taken to gauge adherence to diet.
Intervention code [1] 288608 0
Treatment: Other
Comparator / control treatment
Overweight adults compared to obese adults
Control group
Uncontrolled

Outcomes
Primary outcome [1] 291278 0
Degree of reduction in body weight required to bring about compensatory mechanisms (assessed using weight measurements via calibrated scales, measurements of gut hormones (amylin, PYY, GLP-1, leptin ,ghrelin, GIP,PP and INSL5)glucose, insulin and free fatty acids via serum assays)
Timepoint [1] 291278 0
12 weeks
Primary outcome [2] 291317 0
To investigate if body weight is equally regulated across a range of BMIs (assessed using weight measurements via calibrated scales, measurements of gut hormones (amylin, PYY, GLP-1, leptin ,ghrelin, GIP,PP and INSL5)glucose, insulin and free fatty acids via serum assays)
Timepoint [2] 291317 0
week 64
Secondary outcome [1] 306411 0
Degree of weight regain from week 13-64 (assessed via weight measurements using calibrated scales)
Timepoint [1] 306411 0
week 64
Secondary outcome [2] 306501 0
Change from baseline to week 12; and week 13-64 in gut hormone measurements, fasting glucose measurement, fasting insulin measurement and appetite (as measured by visual analogue scale)(assessed using weight measurements via calibrated scales, measurements of gut hormones (amylin, PYY, GLP-1, leptin ,ghrelin, GIP,PP and INSL5)glucose, insulin and free fatty acids via serum assays)
Timepoint [2] 306501 0
week 64

Eligibility
Key inclusion criteria
*Written informed consent obtained
*Age 18 – 65 years
*BMI 25-50kg/m2
*Stable body weight
*In good health
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
*Body builders
*Significant illness
*History of recent weight loss
*Past history of bariatric surgery
*Use of weight affecting pharmacotherapy
*Current smokers
*History of unstable thyroid disorder

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
The power calculations for this study were based on the expected change in ghrelin levels after weight loss. We propose that average percentage change in ghrelin between the 5% weight loss measurement and 15% weight loss measurement is at least in the vicinity of 0%. To account for natural variation not associated with weight loss we suppose that the percentage change between these two time periods is SD = 25. We assume that equivalence proven if mean percentage change is within +/- 10%. Assuming SD=25%, 70 subjects are required to achieve a power of 90%. To account for attrition, it is proposed that a total recruitment of 100 subjects as an appropriate sample size to study based on an expected attrition rate of 30%.


Additional to the exploration of equivalence between groups, for comparisons between two time points, changes in measurements will be analysed using either a paired t-test or the non-parametric Wilcoxon signed-rank test as appropriate. Changes in hormones and VAS will be analysed using linear mixed effect (lme) models to factor in fixed effects week (i.e. week of visit), time (time of measurement within week), , subject as the random effect and will also allow for adjustment and analysis with respect to covariates. Additionally, changes in hormones will also be modelled using various baseline anthropometric predictors and change in these measures after phase I.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
5/02/2014
Date of last participant enrolment
Anticipated
31/12/2015
Actual
5/06/2015
Date of last data collection
Anticipated
31/12/2018
Actual
Sample size
Target
100
Accrual to date
Final
104
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 1973 0
Austin Health - Heidelberg Repatriation Hospital - Heidelberg West
Recruitment postcode(s) [1] 7702 0
3081 - Heidelberg Heights

Funding & Sponsors
Funding source category [1] 288561 0
University
Name [1] 288561 0
University of Melbourne
Country [1] 288561 0
Australia
Primary sponsor type
University
Name
University of Melbourne
Address
1—100 Grattan Street,
Parkville, Victoria, 3010
Country
Australia
Secondary sponsor category [1] 287275 0
None
Name [1] 287275 0
Address [1] 287275 0
Country [1] 287275 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290423 0
Austin Health HREC
Ethics committee address [1] 290423 0
145 Studley Rd
Heidelberg VIC 3084
Ethics committee country [1] 290423 0
Australia
Date submitted for ethics approval [1] 290423 0
Approval date [1] 290423 0
14/11/2013
Ethics approval number [1] 290423 0
HREC/13/Austin/154

Summary
Brief summary
There is evidence that public health measures aimed at reducing the burden of obesity have not been effective. Whilst there are several possible reasons for this, including a multitude of competing messages, the overabundance of energy dense food and the near absence of obligatory physical activity, it is likely that the more important reason is the fact that weight appears to be physiologically regulated and defended. This means that using public health measures to combat obesity is not likely to work for obese subjects. What is not yet known is if subjects who are overweight (as opposed to obese), defend weight loss, nor is it known if modest (~5%) weight loss is defended. If overweight or modest weight losses are not defended, it would allow the targeting of public health messages towards the overweight and to focus on modest weight loss in the obese.
This study aims to investigate if overweight people defend weight loss as vigorously as obese people, and to determine at what degree of weight loss these physiological changes begin. Overweight and obese people will be recruited and placed on a VLED (very low energy diet) for a period of 12 weeks, aiming to decrease body weight by 15%. Measurements in body weight and a number of biomarkers will be taken at proscribed intervals. All participants will be followed up for a period of two years, to observe weight regain (if any). Gut hormone and other biomarker changes over the trial will be compared between the overweight cohort and the obese cohort, to determine any differences. For both cohorts, changes in gut hormones and other biomarkers will be compared at 5%, 10% and 15% baseline body weight lost, to determine when physiological defences increase.
Trial website
Trial related presentations / publications
Edwards KL, Kalfas S, Prendergast LA, Proietto J. Investigation of the impact of degree of weight loss on physiological adaptations to weight loss.
(Poster presentation at Australian and New Zealand Obesity Society Annual Scientific Meeting 2014)

Kira Edwards, Luke Prendergast, Stefanie Kalfas, Priya Sumithran, Joseph Proietto. Effect of weight loss on plasma INSL5 in humans.
(Poster presentation at the European Congress on Obesity 2017)

Kira Edwards, Luke Prendergast, Stefanie Kalfas, Priya Sumithran, Joseph Proietto. The Relationship between Degree of Weight Loss and Changes in Gut Hormones that Control Hunger and Satiety.
(Oral Presentation at the Australian and New Zealand Obesity Society Annual Scientific Meeting 2017; Finalist, ANZOS Early Career Researcher Awards)
Public notes

Contacts
Principal investigator
Name 45630 0
Prof Joseph Proietto
Address 45630 0
University of Melbourne, Department of Medicine
L2 Boronia Centre, Heidelberg Repatriation Hospital
300 Waterdale Rd
Heidelberg Heights VIC 3081
Country 45630 0
Australia
Phone 45630 0
+61 3 9496 2250
Fax 45630 0
+61 3 9496 2672
Email 45630 0
j.proietto@unimelb.edu.au
Contact person for public queries
Name 45631 0
Ms Kira Edwards
Address 45631 0
University of Melbourne, Department of Medicine
L2 Boronia Centre, Heidelberg Repatriation Hospital
300 Waterdale Rd
Heidelberg Heights VIC 3081
Country 45631 0
Australia
Phone 45631 0
+61 3 9496 2124
Fax 45631 0
+61 3 9496 2672
Email 45631 0
kedwards@unimelb.edu.au
Contact person for scientific queries
Name 45632 0
Prof Joseph Proietto
Address 45632 0
University of Melbourne, Department of Medicine
L2 Boronia Centre, Heidelberg Repatriation Hospital
300 Waterdale Rd
Heidelberg Heights VIC 3081
Country 45632 0
Australia
Phone 45632 0
+61 3 9496 2250
Fax 45632 0
+61 3 9496 2672
Email 45632 0
j.proietto@unimelb.edu.au

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
EmbaseImpact of starting BMI and degree of weight loss on changes in appetite-regulating hormones during diet-induced weight loss.2022https://dx.doi.org/10.1002/oby.23404
N.B. These documents automatically identified may not have been verified by the study sponsor.