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Trial registered on ANZCTR


Registration number
ACTRN12617000304336
Ethics application status
Approved
Date submitted
14/02/2017
Date registered
27/02/2017
Date last updated
15/03/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
The impact of exercise timing (morning vs. evening) on the circadian metabolic systems disrupted in the face of a high fat diet in middle-aged overweight men.

Scientific title
Effects of exercise timing on the deleterious effects of high fat diet on circadian metabolomics in middle/aged overweight men
Secondary ID [1] 291181 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Overweight and obesity 302061 0
Metabolic and endocrine 302081 0
Condition category
Condition code
Diet and Nutrition 301693 301693 0 0
Obesity
Metabolic and Endocrine 301712 301712 0 0
Metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All subjects will eat a high fat diet for 11 days. On day 6 of the high fat diet, subjects in arm 1 and arm 2 will commence the first of five daily exercise sessions finishing on day 10. Subjects in Arm 1 will compete exercise at 7 AM and subjects in Arm 2 at 6 PM.

Overview of design:
Twenty-four sedentary males, body mass index (BMI): 27-35 kg/m2), will be included in a randomised (1:1:1), parallel groups design. There will be two exercise groups (one group exercising in the morning and one in the evening), and a control group.

Materials:
Participants will receive a participant information letter outlining study procedures and a handbook to log physical activity and sleep during the intervention and a daily food checklist.

Procedures:
Experimental conditions will take place at the Exercise Science facilities within the Daniel Mannix Building at Australian Catholic University.

Participants will attend the laboratory on a minimum of 6 days (if allocated to the control group) or 11 days (if allocated to training), as detailed below.

Visit 1: Forms, Resting Metabolic Rate, Dual-Energy X-Ray Absorptiometry (DXA), blood pressure measurements, anthropometry measurements, instructions to complete a three-day food record, exercise pre-screening questionnaire, peak oxygen uptake test (VO2peak).

Visit 2, 2-7 days after visit 1: Continuous glucose monitor inserted, physical activity monitors put on, and food pick-up

Visit 3 and 4 (morning and evening visits for both visits): Muscle biopsies and blood collection, blood pressure measurements, food pick-up. Visit 3 will be the day after visit 2. Visit 4 will be 5 days after visit 3.

Visit 5-9 (only for participants allocated to training): Exercise training sessions, either in the morning or in the evening, depending on group allocation. All sessions will be conducted on a stationary cycle ergometer and supervised by an exercise physiologist. These visits will be on the five consecutive days after visit 4.

Visit 5 (for participants allocated to control, 6 days after visit 4) or Visit 10 (for participants allocated to training, the day following visit 9). Morning and evening visit: muscle biopsies and blood collection, blood pressure measurements.

Visit 6 (for participants allocated to control, 2 days after visit 5) or Visit 11 (for participants allocated to training, 2 days after visit 10): DXA scan, VO2peak, blood pressure measurement.

Description of study procedures:
Resting Metabolic Rate (RMR): Participants will lie down in a quiet, dim-lit room for 25 min where RMR will be measured using an automated gas analyser. A hood (clear) will be placed over the participants head and connected to the gas analyser. The 25 minutes includes a 10 minute rest period, followed by a 15 minute period of data collection.

DXA: participants will undergo a whole body DXA scan. Participants will lay supine on the scanning bed for the duration of the 15 minute scan. There will be one to two scans depending on the body shape of the participant. The machine uses small doses (<1% of the yearly radiation dose) of radiation to estimate tissue density. The total effective dose of radiation has been calculated for this machine and the scans for this study by a Medical Physicist. This test requires the participant be fasted with no food, fluid or exercise/activity prior to the test. Light clothing with no metal items (i.e. zips, domes, clips, underwire etc.) should be worn (gowns are available if need be) and all jewellery must be removed. All measures will be taken by trained researchers who hold radiation licences with Victorian Government and comply to the Code of Practice set out by the Australian Radiation Protection and Nuclear Safety Agency.

Blood pressure: blood pressure (BP) will be measured via an automated BP machine. Three measures will be taken, a minimum of 1 minute apart. Each measure is approximately 3 minutes in duration. The participant will have a cuff applied to the upper portion of the arm. This will inflate and tighten around the arm and then slowly release.

Three-day dietary record: Participants will be given a three day diet record to complete.

Continuous blood glucose monitoring (CGM): participants will be required to wear the minimally invasive Medtronic iPro2 blood glucose monitoring system from visit 2 and until visit 6/11. The monitor is the size of a 50 cent piece and the associated sensor inserted rather painlessly into the subcutaneous tissue of the lower back. The iPro2 will be worn continuously throughout the experimental conditions (16 days).

Physical activity and sleep monitors: to assess physical activity and sleep, participants will be fitted with an inclinometer (ActivPAL3TM) worn on the thigh, an ActiGraph accelerometer worn around the waist, and a SenseWear armband worn on the triceps muscle, to be worn continuously throughout the experiment..

Blood sampling: samples will be collected via a venipuncture into the antecubital vein. A total of 36 mL will be collected each of these days, in total 108 mL from each participant.

Muscle biopsy sampling: skeletal muscle biopsy samples will be obtained from the outer thigh (vastus lateralis) at 7:30 AM and 7:30 PM on three separate days throughout the experimental conditions. The muscle biopsy will be taken by Dr Andrew Garnham. Six muscle biopsies will be obtained from each participant in total.

Exercise: On the first, third, and fifth visit participants will do 10 x 1 min cycling at 85% peak power output (PPO) with one min rest between work intervals at low intensity. The second session and fourth condition will be continuous moderate-intensity cycling for 40 min at 65% PPO (visit 4) and for 60 min at 60% PPO (visit 6).

Dietary control:
During the supervised feeding protocol our accredited research dietitian will create meal plans to provide participants with all meals and snacks. The diet will be a high-fat, low carbohydrate diet containing 65% fat, 15% carbohydrate, 20% protein (including 50 g fibre). Using the RMR collected in the initial visit (Visit 1), participants’ total daily estimated energy requirements will be calculated using RMR x an activity factor of 1.4 to give calories/day. The participants allocated to training will get an extra 100 kcal high-fat snack to consume on training days. During the days of diet control, participants will be instructed to abstain from alcohol. Participants who are habitual caffeine drinkers, will be instructed to consume caffeine as usual on all days. Meal times will be within +/- 30 min of 08:00 am, 13:00, and 19:30 to ensure the trial days are adequately matched. On the days of biopsies, dinner will be at 18:30. Participants will have a single 20 min face-to-face session with the dietitian at visit 1.

Diet adherence will be assessed by a diet checklist, administrated by the dietitian. Exercise adherence will be assessed by exercise intensity, by the supervising exercise physiologist,
Intervention code [1] 297180 0
Treatment: Other
Intervention code [2] 297198 0
Behaviour
Comparator / control treatment
All procedures described in the 'Description of interventions' field will be replicated for the 'no exercise' condition except for the five exercise sessions and consumption of extra food (which is given to the two exercise conditions).
Control group
Active

Outcomes
Primary outcome [1] 301094 0
Circadian metabolic profiling of serum and skeletal muscle tissue (Composite endpoint)
Timepoint [1] 301094 0
Skeletal muscle biopsy sampling will take place at 7:30 AM and 7:30 PM on Visit 3 (Day 3), Visit 4 (Day 8), and visit 5 (for participants in the control group, Day 14)/Visit 10 (for participants in the exercise groups, Day 14).

Blood sampling will be undertaken at the same visits, immediately before the muscle biopsy sampling.
Secondary outcome [1] 331710 0
Blood glucose

Timepoint [1] 331710 0
Blood sampling will take place at 7:15 AM and 7:15 PM on Visit 3 (Day 3), Visit 4 (Day 8), and visit 5 (for participants in the control group, Day 14)/Visit 10 (for participants in the exercise groups, Day 14). Blood glucose will also be continuously measured using continuous glucose monitors throughout the study period.
Secondary outcome [2] 331765 0
Circulating levels of insulin
Timepoint [2] 331765 0
Blood sampling will take place at 7:15 AM and 7:15 PM on Visit 3 (Day 3), Visit 4 (Day 8), and visit 5 (for participants in the control group, Day 14)/Visit 10 (for participants in the exercise groups, Day 14).
Secondary outcome [3] 331766 0
Blood lipids (cholesterol, triglycerids)
Timepoint [3] 331766 0
Blood sampling will take place at 7:15 AM and 7:15 PM on Visit 3 (Day 3), Visit 4 (Day 8), and visit 5 (for participants in the control group, Day 14)/Visit 10 (for participants in the exercise groups, Day 14).
Secondary outcome [4] 331767 0
Ghrelin in blood
Timepoint [4] 331767 0
Blood sampling will take place at 7:15 AM and 7:15 PM on Visit 3 (Day 3), Visit 4 (Day 8), and visit 5 (for participants in the control group, Day 14)/Visit 10 (for participants in the exercise groups, Day 14).
Secondary outcome [5] 331768 0
GLP-1
Timepoint [5] 331768 0
Blood sampling will take place at 7:15 AM and 7:15 PM on Visit 3 (Day 3), Visit 4 (Day 8), and visit 5 (for participants in the control group, Day 14)/Visit 10 (for participants in the exercise groups, Day 14).
Secondary outcome [6] 331769 0
Inflammatory markers in blood, of which not all are pre-specified but potentially including interleukins (e.g. IL-6)
Timepoint [6] 331769 0
Blood sampling will take place at 7:15 AM and 7:15 PM on Visit 3 (Day 3), Visit 4 (Day 8), and visit 5 (for participants in the control group, Day 14)/Visit 10 (for participants in the exercise groups, Day 14).
Secondary outcome [7] 331770 0
Body composition assessed by DXA scan
Timepoint [7] 331770 0
Visit 1 (baseline) and Visit 6 (for participants in the control group, Day 16), or Visit 11 (for participants in the exercise groups, Day 16)
Secondary outcome [8] 331771 0
Peak oxygen uptake assessed by direct measurement of expired gas on a cycle ergometer test
Timepoint [8] 331771 0
Visit 1 (baseline) and Visit 6 (for participants in the control group, Day 16) or Visit 11 (for participants in the exercise group, Day 16)
Secondary outcome [9] 331772 0
Blood pressure
Timepoint [9] 331772 0
Visit 1 (baseline), visits 3 (day 3), visit 4 (Day 8), visit 5 (for participants in the control group, Day 14) or visit 10 (for participants in the exercise groups, Day 14), and visit 6 (for participants in the control group, Day 16) or visit 11 (for participants in the exercise groups, Day 16).
Secondary outcome [10] 331774 0
Enjoyment of physical activity assessed using the Physical Activity Enjoyment Scale (questionnaire)
Timepoint [10] 331774 0
At all exercise sessions for participants in the exercise groups (i.e. at visits 5-9, on days 9-13)

Eligibility
Key inclusion criteria
Male
Aged 30-45 y
BMI: 27-35 kg/m2
Sedentary (in terms of activity and job, less than 150 min/week moderate-intensity exercise for more than 3 months and sitting for more than 5 hours each day)
Able to ride a bicycle for up to 60 min
Minimum age
30 Years
Maximum age
45 Years
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Known cardiovascular disease or diabetes mellitus, major or chronic illness that impairs mobility or eating/digestion; taking prescription medications (i.e. beta-blockers, anti-arrhythmic drugs, statins, or insulin sensitising drugs); habitual physical activity of greater than or equal to 150 min/week of moderate-intensity exercise; previous bariatric surgery; shift workers; smokers; strict dietary intake regimes (i.e. vegan, avoidances of principal study foods); not regularly consuming a breakfast meal; not regularly consuming 3 meals per day (i.e. breakfast, lunch, dinner); current restriction of dietary intake (i.e. actively trying to diet and lose weight); not being weight stable (+/- 5 kg) 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)
Allocation will be concealed as the study personnel are not aware of the randomization procedure. The randomization is administrated by a central administration cite.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomization using a randomization table created by computer software (i.e. computerized 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)
Statistical methods / analysis

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] 15314 0
3065 - Fitzroy

Funding & Sponsors
Funding source category [1] 295621 0
Charities/Societies/Foundations
Name [1] 295621 0
Novo Nordisk Foundation
Address [1] 295621 0
Tuborg Havnevej 19
2900 Helleup
Copenhagen
Country [1] 295621 0
Denmark
Primary sponsor type
Individual
Name
Professor John Hawley
Address
Level 5, 215 Spring St
Centre for Exercise and Nutrition
Mary MacKillop Institute for Health Research
Melbourne, 3000
VICTORIA
Country
Australia
Secondary sponsor category [1] 294462 0
None
Name [1] 294462 0
Address [1] 294462 0
Country [1] 294462 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296941 0
Australian Catholic University Human Research Ethics Committee
Ethics committee address [1] 296941 0
Research Services
Australian Catholic University
Melbourne Campus
Locked Bag 4115
FITZROY VIC 3065
Ethics committee country [1] 296941 0
Australia
Date submitted for ethics approval [1] 296941 0
20/10/2016
Approval date [1] 296941 0
29/11/2016
Ethics approval number [1] 296941 0
2016-254H

Summary
Brief summary
The purpose of the present study is to investigate if exercise can reduce the disruptions to circadian metabolomics observed with the intake of a high fat diet. Additionally, the effect of timing of exercise (i.e. morning vs. evening) will be examined by comparing exercise performed in the morning versus in the evening.

We hypothesise that exercise will reduce the deleterious effects of high-fat diet on circadian metabolomics in overweight/obese individuals. Additionally, this study will give direct insight regarding the effects of timing of exercise on circadian metabolism.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 72494 0
Prof John Hawley
Address 72494 0
Level 5, 215 Spring St
Centre for Exercise and Nutrition
Mary MacKillop Institute for Health Research
Melbourne, 3000
VICTORIA
Country 72494 0
Australia
Phone 72494 0
+61 3 9953 3552
Fax 72494 0
Email 72494 0
john.hawley@acu.edu.au
Contact person for public queries
Name 72495 0
Prof John Hawley
Address 72495 0
Level 5, 215 Spring St
Centre for Exercise and Nutrition
Mary MacKillop Institute for Health Research
Melbourne, 3000
VICTORIA
Country 72495 0
Australia
Phone 72495 0
+61 3 9953 3552
Fax 72495 0
Email 72495 0
john.hawley@acu.edu.au
Contact person for scientific queries
Name 72496 0
Prof John Hawley
Address 72496 0
Level 5, 215 Spring St
Centre for Exercise and Nutrition
Mary MacKillop Institute for Health Research
Melbourne, 3000
VICTORIA
Country 72496 0
Australia
Phone 72496 0
+61 3 9953 3552
Fax 72496 0
Email 72496 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