Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616000144415
Ethics application status
Approved
Date submitted
3/02/2016
Date registered
8/02/2016
Date last updated
8/02/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
Testing of the protein leverage hypothesis (PLH): effect of percent dietary protein on total energy intake in lean healthy adults
Scientific title
Testing of the protein leverage hypothesis (PLH): effect of percent dietary protein on total energy intake in lean healthy adults
Secondary ID [1] 288472 0
nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
obesity 297508 0
Condition category
Condition code
Diet and Nutrition 297705 297705 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Each participant attended three 4-day periods of in-house dietary manipulation. Participants were given ad libitum access to diets containing 10%, 15% and 25% protein over the three 4day periods. Carbohydrate was adjusted to be 60, 55 and 45% energy and dietary fat was kept constant at 30%. Food intake was measured by recording the weight of the food before and after serving, to the nearest gram. Energy intake was calculated using the nutritional information for each recipe. The trial was a randomised crossover-trial, each participant completed each of the three 4-day interventions with at least a one week washout period between interventions.
Intervention code [1] 293808 0
Lifestyle
Comparator / control treatment
The trial was a randomised crossover-trial, each participant participant was their own control
Control group
Active

Outcomes
Primary outcome [1] 297237 0
Energy intake (MJ): Participants were given ad libitum access to study food with no access to other foods during each intervention period. Participants were offered 3 main meals at a designated time each day and had free access to additional study snack foods. Participants were asked to leave any uneaten snack foods and/or empty packages in a designated fridge. Food intake was measured by recording the weight of the food before and after serving to the nearest gram. Total energy intake was then calculated using the nutritional information for each recipe.
Timepoint [1] 297237 0
Weight of food was measured immediately before and after each main meal for each 4-day treatment period. Snack food was weight at the beginning of each day and was monitored and weighed by the study coordinator every 2 hours from 7.30am until 7.30pm. Any leftover or empty packages from snacks consumed overnight (7.30pm-7.30am) were weighed at 7.30am the next day.
Secondary outcome [1] 320421 0
Serum levels of glucose
Timepoint [1] 320421 0
Measured at baseline and on the morning of day 5 following each of the three 4 day interventions.
Secondary outcome [2] 320422 0
Glucose control measured by Continuous Glucose Monitoring System
Timepoint [2] 320422 0
Measured throughout each of the three 4 day interventions.
Secondary outcome [3] 320423 0
Plasma levels of Fibroblast Growth Factor 21 protein.
Timepoint [3] 320423 0
Measured at baseline and on the morning of day 5 following each of the three 4 day interventions
Secondary outcome [4] 320424 0
Plasma levels of total Ghrelin protein
Timepoint [4] 320424 0
On the morning of day 5 following each of the three 4 day interventions.
Secondary outcome [5] 320425 0
Body mass was measured by digital scales.
Timepoint [5] 320425 0
Measured at baseline and on the morning of day 5 following each of the three 4 day interventions.
Secondary outcome [6] 320426 0
Food palatability using visual analogue scales
Timepoint [6] 320426 0
Questionnaires were administered for each food provided on day 4 of each of the 4 day interventions.
Secondary outcome [7] 320427 0
24 hour levels of urinary urea
Timepoint [7] 320427 0
Measured the day prior to and on day 4 of each of the three interventions.
Secondary outcome [8] 320488 0
Serum levels of triglycerides
Timepoint [8] 320488 0
Measured at baseline and on the morning of day 5 following each of the three 4 day interventions.
Secondary outcome [9] 320489 0
Serum levels of total cholesterol
Timepoint [9] 320489 0
Measured at baseline and on the morning of day 5 following each of the three 4 day interventions.
Secondary outcome [10] 320490 0
Serum levels of HDL cholesterol
Timepoint [10] 320490 0
Measured at baseline and on the morning of day 5 following each of the three 4 day interventions.
Secondary outcome [11] 320491 0
Plasma levels of Glucagon Like Polypeptide 1 protein
Timepoint [11] 320491 0
On the morning of day 5 following each of the three 4 day interventions.
Secondary outcome [12] 320492 0
Plasma levels of Cholecystokinin
Timepoint [12] 320492 0
Measured on the morning of day 5 following each of the three 4 day interventions.
Secondary outcome [13] 320494 0
Appetite rating using visual analogue scales
Timepoint [13] 320494 0
Appetite questionnaires were administered hourly from breakfast until 22:00.
Secondary outcome [14] 320502 0
Blood pressure was measured by Omron Standard Blood Pressure Monitor.
Timepoint [14] 320502 0
Measured at baseline and on the morning of day 5 following each of the three 4 day interventions

Eligibility
Key inclusion criteria
Lean, healthy male and female participants.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion criteria included diabetes, high blood pressure, gastrointestinal problems, asthma, eczema or hay fever, chronic medical conditions, anaemia, allergies or strong dislikes to any study foods, smoking, following a weight reducing diet within the 3 months prior to the screening interview, pregnancy and breastfeeding, a history of eating disorders or irregular eating habits. Vegetarian and vegans were excluded to aid in preparation of the intervention foods.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Each subject was screened to determine eligibility for the study. At this point the trial coordinator was unaware of the sequence of interventions the subject would be allocated. Once it was determined that the participant was eligible to be included in the trial the trial coordinator would allocate the participant to a group of subjects that were available to complete the trial on the same dates. When the subjects in each group were finalised the group was then randomly allocated an order of intervention. Allocation of order was concealed by randomly selecting a sequence from an envelope.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
All possible sequences of interventions were printed the same number of times and placed in an envelope prior to the start of the study. The total number of sequences printed exceeded the number of groups that would be required to complete the trial. Once each group was finalised a sequence was randomly selected from the envelope.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Crossover
Other design features
Within subject design, each participant completed each of the interventions. This was an in-house study and each group of subjects remained together throughout the full experiment.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
The study aimed to recruit 24 lean subjects, comprising equal numbers of men and women. The sample size calculation was based on a previous ad libitum study. From this study it was calculated that in order to detect a difference of 0.5MJ given an SE of 0.41, a sample size of 10 gives 92% power and 9 gives 88% power.

One-way within-subject ANOVA and post hoc analysis using the Bonferroni correction for multiple comparisons to test for between treatment effects . Mixed model linear regression to test for significant effects of the interventions and for differences in the change from baseline between each intervention for measurements taken prior to and following each intervention.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
10/01/2008
Date of last participant enrolment
Anticipated
Actual
18/01/2010
Date of last data collection
Anticipated
Actual
Sample size
Target
24
Accrual to date
Final
30
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 5220 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 12692 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 292815 0
Government body
Name [1] 292815 0
National Health and Medical Research Council
Country [1] 292815 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
The University of Sydney, NSW 2006
Country
Australia
Secondary sponsor category [1] 291556 0
Individual
Name [1] 291556 0
Alison Gosby
Address [1] 291556 0
The University of Sydney, NSW 2006
Country [1] 291556 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294320 0
Sydney Local Health District
Ethics committee address [1] 294320 0
Research Development Office
Royal Prince Alfred Hospital
Camperdown, NSW 2050
Ethics committee country [1] 294320 0
Australia
Date submitted for ethics approval [1] 294320 0
28/02/2007
Approval date [1] 294320 0
23/03/2007
Ethics approval number [1] 294320 0
X07-0044
Ethics committee name [2] 294321 0
The University of Sydney Human Research Ethics Committee
Ethics committee address [2] 294321 0
Human Research Ethics Committee
The University of Sydney, NSW 2006
Ethics committee country [2] 294321 0
Australia
Date submitted for ethics approval [2] 294321 0
07/05/2007
Approval date [2] 294321 0
07/06/2007
Ethics approval number [2] 294321 0
10153

Summary
Brief summary
Protein intake has remained relatively stable through the development of the obesity epidemic, yet total energy intake has risen. The protein leverage hypothesis (PLH) proposes that a separate and dominant appetite for protein drives excess energy intake when dietary protein is diluted by fat and carbohydrate. The PLH has been shown in various other species, including non-human primates where excess total energy intake occurs when the percent protein of the diet decreases. Experimental and population-level data also suggest the same may be true in humans (meta-analysis included in the current manuscript). Experimental verification of the protein leverage hypothesis is lacking because it is difficult to separate the role of protein from confounding influences on intake associated with concurrent changes in dietary fat and carbohydrate. The unequivocal test for the PLH is to develop protocols that disguise macronutrient composition of foods offered to subjects under ad libitum feeding conditions. We have recently developed these protocols and in the current study report experiments in which they were applied to confirm the PLH in humans. Here we show that reducing dietary protein by 5% whilst controlling palatability, availability, variety and sensory aspects of the diet resulted in subjects increasing total energy intake by 12%, and this increase was mainly due to increased intake of foods available between meals. We therefore confirm the PLH in humans and show that any change in the nutritional environment that dilutes dietary protein with carbohydrate and fat will promote increased energy intake. Our findings provide a new understanding of a major global health problem, and have considerable implications for the management of obesity.
Trial website
Trial related presentations / publications
Gosby, A. K., Conigrave, A. D., Lau, N. S., Iglesias, M. A., Hall, R. M., Jebb, S. A., et al. (2011). Testing Protein Leverage in Lean Humans: A Randomised Controlled Experimental Study. PLoS One, 6(10).
Public notes

Contacts
Principal investigator
Name 63282 0
Prof Stephen Simpson
Address 63282 0
Charles Perkins Centre, Bldg D17, The University of Sydney, NSW 2006
Country 63282 0
Australia
Phone 63282 0
+61 2 8627 1613
Fax 63282 0
Email 63282 0
[email protected]
Contact person for public queries
Name 63283 0
Alison Gosby
Address 63283 0
Charles Perkins Centre, Bldg D17, The University of Sydney, NSW 2006
Country 63283 0
Australia
Phone 63283 0
+61 2 86271689
Fax 63283 0
Email 63283 0
[email protected]
Contact person for scientific queries
Name 63284 0
Alison Gosby
Address 63284 0
Charles Perkins Centre, Bldg D17, The University of Sydney, NSW 2006
Country 63284 0
Australia
Phone 63284 0
+61 2 86271689
Fax 63284 0
Email 63284 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
EmbaseRaised FGF-21 and triglycerides accompany increased energy intake driven by protein leverage in lean, healthy individuals: A randomised trial.2016https://dx.doi.org/10.1371/journal.pone.0161003
N.B. These documents automatically identified may not have been verified by the study sponsor.