Effects of fat vs. carbohydrate availability on markers of circadian genetics

• Register: ANZCTR
• Last refreshed on: 13 January 2020
• Main ID: ACTRN12616000637448
• Date of registration: 17/05/2016
• Prospective Registration: Yes
• Primary sponsor: Professor John Hawley
• 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
• Date of first enrolment: 20/09/2016
• Target sample size: 10
• Recruitment status: Completed
• URL: https://anzctr.org.au/ACTRN12616000637448.aspx
• Study type: Interventional
• Study design: Purpose: Prevention; Allocation: Randomised controlled trial; Masking: Open (masking not used);Assignment: Crossover;Type of endpoint: Efficacy;
• Phase: Not Applicable

Countries of recruitment

Australia

Contacts

• Name: Dr Evelyn Parr

• Name: Prof John Hawley

Key inclusion & exclusion criteria

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).


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.


Age minimum: 30 Years
Age maximum: 45 Years
Gender: Males

Health Condition(s) or Problem(s) studied

Metabolic and Endocrine - Diabetes

Diet and Nutrition - Obesity

Type 2 diabetes;Obesity;
Type 2 diabetes
Obesity

Intervention(s)

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 p

Primary Outcome(s)

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.[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(s)

Habitual dietary analysis using diet record information from Easy Diet Diary application and timing of meal consumption from time-stamped photos[Seven days of dietary recording prior to each of the two 5 x day diet provision periods]

Protein synthesis genes (using PCR) [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.]

Acitivity monitor analysis (from inclinometer (ActivPal), accelerometer (ActiGraph) and energy expenditure (SenseWear armband) [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]

Change in blood glucose area under the curve using subcutaneous continuous blood glucose monitors, validated with serial finger prick samples.[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.]

Protein expression (using Western Blotting)[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.]

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.[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.]

Body composition using DXA[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]

Resting metabolic rate measured using an online gas analyser whilst resting, fasted in the morning for 45 minutes[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 ID(s)

None

Source(s) of Monetary Support

Novo Nordisk Foundation

Secondary Sponsor(s)

Dr Evelyn Parr

Professor Paolo Sassone-Corsi

Dr Brooke Devlin

Ethics review

Status: Approved
Approval date:
Contact:

Australian Catholic University Human Research Ethics Committee