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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]

None

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Overweight and obesity

Metabolic and endocrine

Condition category

Condition code

Diet and Nutrition

Obesity

Metabolic and Endocrine

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]

Treatment: Other

Intervention code [2]

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]

Circadian metabolic profiling of serum and skeletal muscle tissue (Composite endpoint)

Timepoint [1]

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]

Blood glucose

Timepoint [1]

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]

Circulating levels of insulin

Timepoint [2]

Secondary outcome [3]

Blood lipids (cholesterol, triglycerids)

Timepoint [3]

Secondary outcome [4]

Ghrelin in blood

Timepoint [4]

Secondary outcome [5]

GLP-1

Timepoint [5]

Secondary outcome [6]

Inflammatory markers in blood, of which not all are pre-specified but potentially including interleukins (e.g. IL-6)

Timepoint [6]

Secondary outcome [7]

Body composition assessed by DXA scan

Timepoint [7]

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]

Peak oxygen uptake assessed by direct measurement of expired gas on a cycle ergometer test

Timepoint [8]

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]

Blood pressure

Timepoint [9]

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]

Enjoyment of physical activity assessed using the Physical Activity Enjoyment Scale (questionnaire)

Timepoint [10]

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

Sex

Males

Can healthy volunteers participate?

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

6/03/2017

Actual

20/03/2017

Date of last participant enrolment

Anticipated

14/08/2017

Actual

20/07/2017

Date of last data collection

Anticipated

31/08/2017

Actual

8/08/2017

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment postcode(s) [1]

3065 - Fitzroy

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Novo Nordisk Foundation

Address [1]

Tuborg Havnevej 19
2900 Helleup
Copenhagen

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Australian Catholic University Human Research Ethics Committee

Ethics committee address [1]

Research Services
Australian Catholic University
Melbourne Campus
Locked Bag 4115
FITZROY VIC 3065

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

20/10/2016

Approval date [1]

29/11/2016

Ethics approval number [1]

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

Prof John Hawley

Address

Level 5, 215 Spring St
Centre for Exercise and Nutrition
Mary MacKillop Institute for Health Research
Melbourne, 3000
VICTORIA

Country

Australia

Phone

+61 3 9953 3552

Fax

[email protected]

Contact person for public queries

Name

Prof John Hawley

Address

Level 5, 215 Spring St
Centre for Exercise and Nutrition
Mary MacKillop Institute for Health Research
Melbourne, 3000
VICTORIA

Country

Australia

Phone

+61 3 9953 3552

Fax

[email protected]

Contact person for scientific queries

Name

Prof John Hawley

Address

Level 5, 215 Spring St
Centre for Exercise and Nutrition
Mary MacKillop Institute for Health Research
Melbourne, 3000
VICTORIA

Country

Australia

Phone

+61 3 9953 3552

Fax

[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

Source	Title	Year of Publication	DOI
Embase	The effect of morning vs evening exercise training on glycaemic control and serum metabolites in overweight/obese men: a randomised trial.	2021	https://dx.doi.org/10.1007/s00125-021-05477-5

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically