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Trial registered on ANZCTR


Registration number
ACTRN12616000637448
Ethics application status
Approved
Date submitted
11/05/2016
Date registered
17/05/2016
Date last updated
16/01/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Effects of fat vs. carbohydrate availability on markers of circadian genetics
Scientific title
Effects of high fat vs. high carbohydrate diets on markers of circadian genetics in sedentary overweight and obese men
Secondary ID [1] 289181 0
None
Universal Trial Number (UTN)
U1111-1182-7841
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 diabetes 298732 0
Obesity 298733 0
Condition category
Condition code
Diet and Nutrition 298779 298779 0 0
Obesity
Metabolic and Endocrine 298780 298780 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study will employ two conditions, administered in a randomized design, for each participant. One condition will involve participants being on a high fat, low carbohydrate diet (Condition A) for five days. The other condition will involve participants being on a high carbohydrate, low fat diet (Condition B) for five days. Dietary interventions will be separated by a one week washout and all food for each intervention period will be provided prior to the consumption period. Skeletal muscle biopsies will be collected in the morning (8 am) and at night (8 pm) on day 5 of each diet regime, as well as at the end of a 7 day food diary period of each participants typical dietary intake (to establish individual baselines) prior to each dietary intervention - i.e. eight biopsies per person in total over the trials.
To achieve this, participants will complete 8 x 2.5 h visits to the laboratory. During each morning visit, DXA (for body composition), resting metabolic rate (RMR) and a blood sample will be measured. Following from these a single muscle biopsy will be obtained. Participants will then be free to leave the laboratory and will return in the evening. For each evening visit, a blood sample and a muscle biopsy will be obtained.

An initial RMR and DXA measure, prior to each baseline period of 7 day food record, will be used to calculate participants energy requirements for the provided dietary periods.

Throughout the two x 7 day baseline measurement periods and each of the two x 5 day periods of dietary modification, participants will wear activity and glucose monitors and record their dietary intake.

Condition A: Dietary intake will be a high fat diet, with a composition of 65% energy from fat, 15% energy from carbohydrate and 20% energy from protein
Condition B: Dietary intake will be a high carbohydrate diet, with a composition of 65% energy from carbohydrate, 15% energy from fat and 20% energy from protein
Intervention code [1] 294710 0
Lifestyle
Intervention code [2] 294731 0
Prevention
Comparator / control treatment
The participants act as their own control (where Condition A is the control condition) and complete both dietary conditions.
Control group
Active

Outcomes
Primary outcome [1] 298252 0
Metabolomics analysis of serum, plasma and skeletal muscle tissue using mass spectrometry of Lipids (fatty acids, lysolipids, phospholipids, sphingolipids, eicosanoids, monoacylglycerols, diacylglycerols, sterols, steroids, bile acid, polyunsaturated Fatty Acid (n3 and n6), endocannabinoid), Amino Acids (creatine/guanidine/acetamido metabolism, histidine metabolism, lysine metabolism, methionine/cysteine/SAM metabolism, phenylalanine/tyrosine metabolism, leucine/isoleucine/valine metabolism, tryptophan metabolism, alanine/aspartate metabolism, urea cycle products, and polyamine metabolism products), Nucleotides (pyrimidine and purine metabolism products), Energy (glycolysis, gluconeogenesis and TCA cycle metabolites), Carbohydrates (pentose metabolism, aminosugar metabolism, fructose/mannose/galactose metabolism, advanced glycation end products) and Cofactors and Vitamins (nicotinate/nicotinamide metabolism, ascorbate/aldarate metabolism, pantothenate/CoA metabolism, vitamin B metabolites, vitamin A, riboflavin). This is a composite analysis.
Timepoint [1] 298252 0
Morning (~8 am) and night (~8 pm) muscle, serum and plasma samples from both baseline days prior to the dietary interventions, day 5 of the high fat diet and day 5 of the high carbohydrate diet.
Secondary outcome [1] 323661 0
Body composition using DXA
Timepoint [1] 323661 0
Measured pre-study for energy calculations, then measured at the end of each baseline dietary period (morning of the 7th day), and on the morning of day 5 of each condition
Secondary outcome [2] 323662 0
Resting metabolic rate measured using an online gas analyser whilst resting, fasted in the morning for 45 minutes
Timepoint [2] 323662 0
Measured pre-study for energy calculations, then measured at the end of each baseline dietary period (morning of the 7th day), and on the morning of day 5 of each condition
Secondary outcome [3] 323664 0
Blood profiles (including glucose, lactate, ketones, insulin, triglycerides, cholesterol, ghrelin, GLP-1, inflammation markers and other metabolic markers) measured using plasma samples either immediately (glucose, lactate, triglycerides, cholesterol, ketones) or stored at -80 degrees celcius and measured using ELISA assay (ghrelin, GLP-1, inflammatory markers (e.g. IL-6, and other metabolic markers). This is a composite secondary outcome.
Timepoint [3] 323664 0
Measured at 8 am and 8 pm of each of the two baseline testing sessions, day 5 of the high fat diet and day 5 of the high carbohydrate diet using plasma samples.
Secondary outcome [4] 323666 0
Protein synthesis genes (using PCR)
Timepoint [4] 323666 0
Measured at 8 am and 8 pm of each of the two baseline testing sessions, day 5 of the high fat diet and day 5 of the high carbohydrate diet using plasma samples.
Secondary outcome [5] 323731 0
Protein expression (using Western Blotting)
Timepoint [5] 323731 0
Measured at 8 am and 8 pm of each of the two baseline testing sessions, day 5 of the high fat diet and day 5 of the high carbohydrate diet using plasma samples.
Secondary outcome [6] 336880 0
Change in blood glucose area under the curve using subcutaneous continuous blood glucose monitors, validated with serial finger prick samples.
Timepoint [6] 336880 0
For assessment of baseline (i.e. from insertion at day-7 to day 0) habitual glucose patterns, including the 3-h postprandial periods, as well as the dietary provision periods (High fat diet vs High carbohydrate diet) from Day 1 to day 5) with finger prick validation samples at 1 h post insertion (i.e. 5 pm of the day before), prior to breakfast, prior to lunch, prior to dinner and the morning after the trial.
Secondary outcome [7] 342054 0
Habitual dietary analysis using diet record information from Easy Diet Diary application and timing of meal consumption from time-stamped photos
Timepoint [7] 342054 0
Seven days of dietary recording prior to each of the two 5 x day diet provision periods
Secondary outcome [8] 342055 0
Acitivity monitor analysis (from inclinometer (ActivPal), accelerometer (ActiGraph) and energy expenditure (SenseWear armband)
Timepoint [8] 342055 0
Measured during the habitual periods (2 x 7 days) and the experimental diet periods (2 x 5 days). Also focusing on the 3 hour postprandial meal periods to couple with blood glucose and dietary data

Eligibility
Key inclusion criteria
Overweight or obese as defined by a BMI between 27-32.5 kg/m2
Sedentary (for both occupation and recreational time - no more than 150 minutes of regular physical activity during a week, typical television watching time >3 h per day).

Minimum age
30 Years
Maximum age
45 Years
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Major or chronic illness that impairs mobility or eating/digestion/metabolism (i.e. type 2 diabetes, cancer, gastrointestinal disorders); previous bariatric surgery; shift workers; smokers; individuals with strict dietary intake regimes (i.e. vegan, avoidance of principal study foods); individuals who do not regularly consume a breakfast meal; individuals who do not have a regular dietary pattern of meals (i.e. breakfast, lunch, dinner); individuals who are currently restricting their dietary intake (i.e. actively trying to diet and lose weight); individuals who have not been weight stable for the last 3 months.

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)
Sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using computer-generated, randomised sequence. An independent third party will prepare the computer-generated randomisation lists and sealed envelopes for randomisation. Once informed consent is obtained, the sealed randomisation envelope will be opened revealing the trial-condition order.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
This study will be the first of its kind to be able to measure circadian metabolomics in human muscle tissue and therefore we do not have anything to gauge the differences we may see from other research.
Our previous studies of high fat vs high carbohydrate diets with exercise have used sample sizes of 8 participants in order to observe changes at rest in enzyme activity associated with aerobic metabolism and substrate utlisation (see Yeo et al., Appl. Physiol. Nutr. Metab. 2011; 36: 12–22). To account for the potential participant dropout, 10 participants will be recruited

Data from the two conditions (High fat, low carbohydrate and high carbohydrate, low fat) will be analysed using Generalised Linear Mixed Models, with baseline measures of dietary intake, body fatness, resting metabolic rate, age etc. as covariates.
Statistical significance will be set at p<0.05.
Statistical analysis will be undertaken using SPSS (Version 22 for Windows, SPSS Inc, Chicago, IL).

Recruitment
Recruitment status
Completed
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)
VIC
Recruitment postcode(s) [1] 13231 0
3065 - Fitzroy
Recruitment postcode(s) [2] 13232 0
3000 - Melbourne

Funding & Sponsors
Funding source category [1] 293568 0
Charities/Societies/Foundations
Name [1] 293568 0
Novo Nordisk Foundation
Address [1] 293568 0
Tuborg Havnevej 19
2900 Hellerup
Country [1] 293568 0
Sweden
Primary sponsor type
Individual
Name
Professor John Hawley
Address
Level 5, 215 Spring Street
Centre for Exercise and Nutrition
Mary MacKillop Institute for Health Research
Melbourne, 3000 VIC
Country
Australia
Secondary sponsor category [1] 292388 0
Individual
Name [1] 292388 0
Dr Evelyn Parr
Address [1] 292388 0
Level 5, 215 Spring Street
Centre for Exercise and Nutrition
Mary MacKillop Institute for Health Research
Melbourne, 3000 VIC
Country [1] 292388 0
Australia
Secondary sponsor category [2] 292389 0
Individual
Name [2] 292389 0
Professor Paolo Sassone-Corsi
Address [2] 292389 0
The Center for Epigenetics & Metabolism
324 Sprague Hall
Irvine, CA 92697-4049
Country [2] 292389 0
United States of America
Secondary sponsor category [3] 292390 0
Individual
Name [3] 292390 0
Dr Brooke Devlin
Address [3] 292390 0
Level 5, 215 Spring Street
Centre for Exercise and Nutrition
Mary MacKillop Institute for Health Research
Melbourne, 3000 VIC
Country [3] 292390 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295012 0
Australian Catholic University Human Research Ethics Committee
Ethics committee address [1] 295012 0
Manager, Ethics
c/o Office of the Deputy Vice Chancellor (Research)
Australian Catholic University
North Sydney Campus
PO Box 968
NORTH SYDNEY, NSW 2059
Ethics committee country [1] 295012 0
Australia
Date submitted for ethics approval [1] 295012 0
24/03/2016
Approval date [1] 295012 0
16/06/2016
Ethics approval number [1] 295012 0
2016-77H

Summary
Brief summary
Presently there is a large push in the non-scientific nutrition-diet community towards a high-fat diet for improving any disease state, with very little scientific evidence. In fact, research in animals (rats) has shown the negative effects of the high-fat, low carbohydrate diet to glucose regulation and weight management. In line with this research, much of the circadian rhythm and metabolomics literature published to date has been using animal models and no human data exists in this area. Establishing the circadian profile in a healthy middle aged population will act to inform future diet and exercise training studies. Currently, there are no dietary studies of circadian clock genes in humans and with increasing rates of type 2 diabetes and obesity, dietary alterations are common within today’s society that the consequences of such changes are not well understood.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 65762 0
Prof John Hawley
Address 65762 0
Level 5, 215 Spring Street
Mary MacKillop Institute for Health Research
Australian Catholic University
Melbourne 3000 VIC
Country 65762 0
Australia
Phone 65762 0
+61 3 9553 3552
Fax 65762 0
Email 65762 0
john.hawley@acu.edu.au
Contact person for public queries
Name 65763 0
Dr Evelyn Parr
Address 65763 0
Level 5, 215 Spring Street
Mary MacKillop Institute for Health Research
Australian Catholic University
Melbourne 3000 VIC
Country 65763 0
Australia
Phone 65763 0
+61 3 9230 8278
Fax 65763 0
Email 65763 0
evelyn.parr@acu.edu.au
Contact person for scientific queries
Name 65764 0
Prof John Hawley
Address 65764 0
Level 5, 215 Spring Street
Mary MacKillop Institute for Health Research
Australian Catholic University
Melbourne 3000 VIC
Country 65764 0
Australia
Phone 65764 0
+61 3 9553 3552
Fax 65764 0
Email 65764 0
john.hawley@acu.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary