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Trial registered on ANZCTR


Registration number
ACTRN12612000651886
Ethics application status
Approved
Date submitted
7/06/2012
Date registered
19/06/2012
Date last updated
11/11/2020
Date data sharing statement initially provided
13/06/2019
Date results information initially provided
13/06/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
The TEMPO Diet Trial: Type of Energy Manipulation for Promoting optimum metabolic health and body composition in Obesity
Scientific title
Long-term effects of very low energy diet versus conventional diet on adiposity, lean body mass, muscle strength and bone density in obese adults (postmenopausal women), and mechanisms promoting changes
Secondary ID [1] 280385 0
Nil
Universal Trial Number (UTN)
U1111-1130-1982
Trial acronym
The TEMPO Diet Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obesity 286364 0
Cardiovascular disease 286365 0
Sarcopenia 286366 0
Osteoporosis 286367 0
Neuroendocrine function 286368 0
Condition category
Condition code
Diet and Nutrition 286608 286608 0 0
Obesity
Metabolic and Endocrine 286609 286609 0 0
Normal metabolism and endocrine development and function
Musculoskeletal 286610 286610 0 0
Normal musculoskeletal and cartilage development and function

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Two 12-month dietary interventions will be compared: very low energy diet (VLED) and conventional diet. The VLED is an approximately 2,100 kilojoule (500 calorie) per day diet consisting of meal replacement shakes, bars or desserts. No other foods will be consumed during the VLED except for low calorie jelly, strained broth and certain vegetables. The VLED will be used for a minimum of 3 months and a maximum of 5 months, after which time participants will switch to either a partial meal replacement program for further weight loss if required (~1,500 kcal per day), or the conventional diet for weight maintenance for the remainder of the 12 months. The conventional diet is a lifestyle weight management program consisting of moderate kilojoule restriction (~500 kcal deficit per day) and involves general recommendations for healthy eating such as increasing fruit and vegetable intake and reducing the intake of processed or fatty foods (e.g. cakes, chocolate, visible fat on meat, etc).
Intervention code [1] 284750 0
Lifestyle
Intervention code [2] 285110 0
Treatment: Other
Intervention code [3] 285112 0
Prevention
Comparator / control treatment
Effects of the very low energy diet will be compared to effects of the conventional diet. The conventional diet will be deemed as the 'control' in this study.
Control group
Active

Outcomes
Primary outcome [1] 287259 0
Body weight and composition:

* Body weight / body mass index
* Fat mass and fat distribution
* Fat free mass
* Thigh muscle diameter
* Bone mass

Methods: Weight will be measured with scales; height (stretch stature) will be measured with a stadiometer for calculation of body mass index; fat mass, fat free mass and bone mass will be determined with the 4-compartment model for assessment of body composition, comprising independent measures of body density (using the BodPod, Cosmed, Italy), total body water using the deuterium dilution technique, and dual energy X-ray absorptiometry (DXA, Hologic, Bedford, MA, USA); fat distribution (abdominal obesity) will be estimated from investigation of DXA scans between lumbar vertebrae L2 and L4 and L3 and L6. Additionally, we will use a Siemens Sonata (Malvern, PA, USA) 1.5 Tesla magnet to determine total, visceral and subcutaneous adiposity by magnetic resonance imaging (MRI). MRI will also be used to determine thigh muscle diameter at the midpoint between the patella and inguinal crease.
Timepoint [1] 287259 0
0, 3, 6, 12, 24 and 36 months after commencement of either diet
Primary outcome [2] 287349 0
Parameters that affect body composition (adaptive responses to energy restriction):

* Resting metabolic rate
* Neuroendocrine status (i.e. thyroid hormone function)

Methods: Resting metabolic rate will be measured in the morning in the fasted state with indirect calorimetry using the TrueOne 2400 (Parvo Medics, Sandy, UT, USA) ventilated hood. Thyroid hormone function will be assessed by determining the circulating concentrations of thyroid stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4) and reverse T3 in morning blood samples collected in the fasted state. Commercial kits or pathology services will be used for these analyses of thyroid function.
Timepoint [2] 287349 0
0, 0.25, 1, 3, 6 and 12 months after commencement of either diet
Secondary outcome [1] 297759 0
Other indices of body composition:

* Waist circumference
* Hip circumference
* Hepatic fat
* Thigh fat
* Muscle strength

Methods: Waist and hip circumference will be determined using a tape measure. We will use a Siemens Sonata (Malvern, PA, USA) 1.5 Tesla magnet to determine hepatic fat content by magnetic resonance spectroscopy (MRS) as well as magnetic resonance imaging (MRI) to determine thigh fat at the midpoint between the patella and inguinal crease. Muscle strength will be determined using a Jamar hydraulic hand dynamometer (Lafayette Instrument Company, Lafayette, IN, USA).
Timepoint [1] 297759 0
0, 3, 6, 12, 24 and 36 months after commencement of either diet
Secondary outcome [2] 297760 0
Parameters of metabolic health:

* Fasting serum glucose
* Fasting serum insulin
* Fasting serum triglycerides
* Fasting serum cholesterol
* Fasting blood glycosylated hemoglobin
* Fasting serum C-reactive protein
* Blood pressure
Timepoint [2] 297760 0
0, 3, 6, 12, 24 and 36 months after commencement of either diet
Secondary outcome [3] 297761 0
Vascular function:

* Flow mediated dilatation
* EndoPAT
* Carotid intima-media thickness
* Pulse wave velocity
Timepoint [3] 297761 0
0, 3, 6, and 36 months after commencement of either diet
Secondary outcome [4] 297762 0
Other parameters that affect body composition (adaptive responses to energy restriction):

* Appetite
* Physical activity
* Neuroendocrine status (e.g. fasting serum concentrations of ACTH, cortisol, LH, FSH, estradiol, IGF-1 etc)
* Fasting serum gut hormone concentrations
* Circulating or urinary markers of bone turnover
* Sympathetic reactivity
* Fasting serum ketone bodies

Methods: Appetite will be assessed using visual analogue scales. Appetite will be measured in the morning after an overnight fast, as well as after a small breakfast meal that participants on the very low energy diet would usually eat as part of their diet. Physical activity will be assessed using Actigraph GT1M accelerometers, worn for 7 days prior to each time point, as well as by a questionnaire on physical activity. Concentrations of hormones, bone turnover markers and ketone bodies will be determined using commercial assay kits or pathology services. Sympathetic reactivity will be assessed by inspiration-induced vasoconstriction, as determined by laser Doppler fluximetry (MoorVMS-LDF Laser Doppler Blood Flow Monitor, Moor, England).
Timepoint [4] 297762 0
0, 0.25, 1, 3, 6 and 12 months after commencement of either diet
Secondary outcome [5] 297763 0
Effect of the ketotic state during a very low energy diet on the adaptive responses to energy restriction:

* Appetite
* Physical activity
* Resting metabolic rate
* Neuroendocrine status (e.g. fasting serum concentrations of thyroid hormones, ACTH, cortisol, LH, FSH, estradiol, IGF-1 etc)
* Fasting serum gut hormone concentrations
* Sympathetic reactivity
* Fasting serum ketone bodies

Methods: Please see Primary outcome 2 and Secondary outcome 4.
Timepoint [5] 297763 0
3.25 months after commencement of the VLED (corresponding to 1 week after switching to a non-ketogenic maintenance diet)

Only those participants in the VLED arm will undergo this sub-study. Following measurement of the adaptive responses to weight loss at 3 months as described above (at which point all participants will still be on the VLED, which results in ketosis due to its low carbohydrate & kilojoule content), volunteers will switch to a maintenance diet for 1 week followed by re-measurement at t = 3.25 months.

Eligibility
Key inclusion criteria
* Sedentary (< 60 minutes physical activity / week)
* Class I or II obesity (30-40 kg.m2)
* At least 5 years post-menopausal
Minimum age
45 Years
Maximum age
65 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
* Hypothyroidism or hyperthyroidism
* Diabetes
* Osteoporosis
* Smoker
* Non-ambulatory
* Gained or lost more than 2 kg in the last 6 months
* Taking medications known to affect heart rate, body composition or bone mass (e.g. glucocorticoids or beta blockers)
* Have taken anti-resorptive therapy within the last 3 years
* Alcohol or drug dependency
* Presence of metal in the body (e.g. from a pacemaker)

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 stratified according to BMI (30-34.9, 35-40 kg/m2) and age (45-54, 55-65 years) and then randomly allocated to either the VLED or the conventional diet. Allocation will not be concealed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation. Where VLED = 1 and conventional diet = 2. Where BMI (30-34.9 kg/m2) = A, BMI (35-40 kg/m2) = B, Age (45-54 years) = C, Age (55-65 years) = D. Each participant will therefore fall into one of four cell options: AC, AD, BC or BD. Each cell will have pair allocations of random sequence 1 or 2.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
2/09/2012
Actual
24/03/2014
Date of last participant enrolment
Anticipated
Actual
28/07/2016
Date of last data collection
Anticipated
31/10/2019
Actual
20/09/2019
Sample size
Target
100
Accrual to date
Final
101
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 285154 0
Government body
Name [1] 285154 0
National Health & Medical Research Council
Country [1] 285154 0
Australia
Primary sponsor type
Government body
Name
Sydney Local Health District
Address
Royal Prince Alfred Hospital
Missenden Road
Camperdown NSW 2050
Country
Australia
Secondary sponsor category [1] 284230 0
None
Name [1] 284230 0
None
Address [1] 284230 0
None
Country [1] 284230 0
Other collaborator category [1] 260773 0
Individual
Name [1] 260773 0
Professor Amanda Sainsbury-Salis
Address [1] 260773 0
The Boden Institute of Obesity, Nutrition, Exercise & Eating Disorders, Charles Perkins Centre, John Hopkins Drive, The University of Sydney, NSW, 2006
Country [1] 260773 0
Australia
Other collaborator category [2] 260774 0
Individual
Name [2] 260774 0
Professor Nuala Byrne
Address [2] 260774 0
Bond Institute of Health and Sport
Faculty of Health Sciences & Medicine
Bond University
Gold Coast QLD 4229
Country [2] 260774 0
Australia
Other collaborator category [3] 276841 0
Individual
Name [3] 276841 0
Professor Ian Caterson
Address [3] 276841 0
The Boden Institute of Obesity, Nutrition, Exercise & Eating Disorders
G85 Medical Foundation Building K25
The University of Sydney
NSW 2006
Country [3] 276841 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287170 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 287170 0
Royal Prince Alfred Hospital
50 Missenden Road
Camperdown
NSW 2050
Ethics committee country [1] 287170 0
Australia
Date submitted for ethics approval [1] 287170 0
12/03/2012
Approval date [1] 287170 0
03/05/2012
Ethics approval number [1] 287170 0
X12-0081 & HREC/12/RPAH/135

Summary
Brief summary
For many years health professionals have recommended ‘slow and steady’ weight loss. Recently however an increasing number of health professionals have begun prescribing very low energy diets (VLEDs) for the management of excess body weight. VLEDs can induce fast weight losses of approximately 0.5 to 2 kilos per week, which some people find motivating. Moreover, some people report not feeling hungry while on a VLED.

While VLEDs are known to be safe and effective in the short-term, the long-term consequences are unknown. There is some concern that compared to slower weight loss, VLEDs may increase the likelihood of weight regain, particularly in the abdominal region, and this could increase the risk of cardiovascular disease. Additionally, VLEDs may cause greater losses of muscle mass, muscle strength and bone density compared to slower ‘conventional diets’, but this has never been tested.

This study will demonstrate whether or not there are any differences between VLED and conventional diet with respect to effects on body fat content and distribution, muscle mass, muscle strength or bone density for up to 3 years after commencement of either diet.
Trial website
http://sydney.edu.au/medicine/research/units/boden/clinical-trials.php#tempo
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34106 0
Prof Amanda Sainsbury-Salis
Address 34106 0
The Boden Institute of Obesity, Nutrition, Exercise & Eating Disorders, Charles Perkins Centre, John Hopkins Drive, The University of Sydney, NSW, 2006
Country 34106 0
Australia
Phone 34106 0
+61 4 23777801
Fax 34106 0
Email 34106 0
[email protected]
Contact person for public queries
Name 17353 0
Prof Professor Amanda Sainsbury-Salis
Address 17353 0
The Boden Institute of Obesity, Nutrition, Exercise & Eating Disorders, Charles Perkins Centre, John Hopkins Drive, The University of Sydney, NSW, 2006
Country 17353 0
Australia
Phone 17353 0
+61 4 23777801
Fax 17353 0
Email 17353 0
[email protected]
Contact person for scientific queries
Name 8281 0
Prof Professor Amanda Sainsbury-Salis
Address 8281 0
The Boden Institute of Obesity, Nutrition, Exercise & Eating Disorders, Charles Perkins Centre, John Hopkins Drive, The University of Sydney, NSW, 2006
Country 8281 0
Australia
Phone 8281 0
+61 4 23777801
Fax 8281 0
Email 8281 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All outcomes, subject to application.
When will data be available (start and end dates)?
Anticipated from June 2020 onward (no end date)
Available to whom?
Researchers who explain the reason for requesting the data, and who include relevant members of our team in the publication process.
Available for what types of analyses?
Unrestricted.
How or where can data be obtained?
Will be sent after signing data access agreement.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
2338Study protocol    Seimon RV, Gibson AA, Harper C, Keating SE, Johnso... [More Details]



Results publications and other study-related documents

Documents added manually

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseFast versus slow weight loss: development process and rationale behind the dietary interventions for the TEMPO Diet Trial.2016https://dx.doi.org/10.1002/osp4.48
EmbaseEffect of severe compared with moderate energy restriction on physical activity among postmenopausal female adults with obesity: a prespecified secondary analysis of the Type of Energy Manipulation for Promoting optimum metabolic health and body composition in Obesity (TEMPO) Diet randomized controlled Trial.2022https://dx.doi.org/10.1093/ajcn/nqac024
EmbasePostmenopausal women's experiences of weight maintenance following a very low energy diet.2023https://dx.doi.org/10.1002/osp4.654
EmbaseUrine dipsticks are not accurate for detecting mild ketosis during a severely energy restricted diet.2020https://dx.doi.org/10.1002/osp4.432
N.B. These documents automatically identified may not have been verified by the study sponsor.