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Trial registered on ANZCTR


Registration number
ACTRN12619001222134
Ethics application status
Approved
Date submitted
2/07/2019
Date registered
4/09/2019
Date last updated
15/11/2019
Date data sharing statement initially provided
4/09/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Combined effects of timing of eating and exercise on blood sugar control in individuals with type 2 diabetes
Scientific title
Combined effects of time-restricted eating and exercise on postprandial metabolism in individuals with type 2 diabetes
Secondary ID [1] 298620 0
None
Universal Trial Number (UTN)
U1111-1236-0877
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 diabetes 313481 0
Overweight/Obesity 313482 0
Condition category
Condition code
Metabolic and Endocrine 311908 311908 0 0
Diabetes
Diet and Nutrition 311909 311909 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
In a randomised, cross-over design (with a 6-day washout period between each), participants will complete four trial conditions (including one control condition) where they attend the laboratory between 7 am and 10 pm to have serial blood samples taken and subsequently measured and all meals provided through the following conditions:
1) A normal "control" eating condition (eating all meals within 12 h; at 8 am, 2 pm and 8 pm);
2) Exercise breaks (3 x 15 min walking bouts on a treadmill at 60% VO2peak, each in the 45 min - 1 hour post meal periods (i.e. 15 min exercise after each meal) with a control eating condition (eating all meals within 12 h, at 8 am, 2 pm and 8 pm);
3) Time-restricted eating condition (eating all meals within 8 h; at 10 am, 2 pm and 6 pm);
4) Exercise breaks (3 x 15 min walking bouts on a treadmill at 60% VO2peak, each in the 45 min - 1 hour post meal periods (i.e. 15 min exercise after each meal) with time-restricted eating (eating all meals within 8 h, at 10 am, 2 pm and 6 pm).

In all conditions, except for exercise times, participants will remain seated and will be provided the opportunity to move during standardised toilet breaks throughout the day and may bring books or computers etc to entertain themselves between measures in all conditions.

All meals will be provided at standardised times (#1/2: 8 am, 2 pm and 8 pm; #3/4: 10 am, 2 pm and 6 pm) and each meal will be of similar composition to typical macronutrient intake of ~50% carbohydrate, ~30% fat and ~20% protein. All meals will be designed by an accredited practicing dietitian and will be of the same foods for all participants, but calculated for energy intake relative to each individuals total daily energy requirements (as determined by resting metabolic rate multiplied by an activity factor of 1.4). No snacks will be provided but water can be consumed ad libitum in the first trial and will be repeated in the subsequent trials.
Intervention code [1] 314879 0
Lifestyle
Intervention code [2] 314880 0
Behaviour
Intervention code [3] 315272 0
Treatment: Other
Comparator / control treatment
1) A normal "control" eating condition (eating all meals within 12 h).

All meals will be provided at standardised times (control = 8 am, 2 pm and 8 pm) and each meal will be of similar composition to typical macronutrient intake of ~50% carbohydrate, ~30% fat and ~20% protein. All meals will be designed by an accredited practicing dietitian and will be of the same foods for all participants, but calculated for energy intake relative to each individuals total daily energy requirements (as determined by resting metabolic rate multiplied by an activity factor of 1.4).
Control group
Active

Outcomes
Primary outcome [1] 320579 0
Area under the curve for interstitial glucose concentrations, measured using continuous glucose monitors, across each condition for 24-hours
Timepoint [1] 320579 0
Measured continuously from 7:30 am to 7:30 am for 24 hours (including 14 hours in the laboratory).
Secondary outcome [1] 372098 0
Area under the curve for venous insulin concentrations across each condition for 14-hours
Timepoint [1] 372098 0
Measured every hour from 8 am to 10 pm, and collected every 30 min for 2 hours after each meal.
Secondary outcome [2] 372099 0
Area under the curve for venous glucose concentrations across each condition for 14-hours
Timepoint [2] 372099 0
Measured every hour from 8 am to 10 pm, and collected every 30 min for 2 hours after each meal (total of 26 measures).
Secondary outcome [3] 372100 0
Brachial arterial blood pressure will be measured every hour across each condition using an automated oscillatory blood pressure monitor (Welch Allyn Connex 3400 ProBP Automatic Blood Pressure Machine).
Timepoint [3] 372100 0
Measured every hour from 8 am to 10 pm in each condition
Secondary outcome [4] 372101 0
Cognitive performance will be assessed using a battery of cognitive tasks performed on a laptop (using Cogstate)
Timepoint [4] 372101 0
Cognitive tasks will be assessed at 6 timepoints throughout the 14 hour laboratory visit; for all conditions cognition will be assessed at baseline (~7.30 am), pre-lunch (i~1.30 pm), post-lunch (~3.30 pm); further, the other three timepoints will be made at times relative to the meal conditions, i.e. post-breakfast (~11.30 am in TRE groups and ~9.30 am in control groups), pre-dinner (~5.30 pm in TRE groups and ~7.30 pm in control groups), and post dinner (~7.30 pm for TRE groups and ~9.30 pm for control groups).
Secondary outcome [5] 372103 0
Blood lipids (composite measure using Cobas disc of total cholesterol, triglycerides, HDL cholesterol and LDL cholesterol (calculated))
Timepoint [5] 372103 0
Every hour across the 14 hour laboratory stay and one fasting sample the following day
Secondary outcome [6] 372107 0
Self-reported fatigue will be collected using visual analogue scales (score between 0 - 100)
Timepoint [6] 372107 0
Measured every 2 h throughout the 14 h conditions
Secondary outcome [7] 372108 0
Self-reported appetite will be collected using visual analogue scales (score between 0 - 100)
Timepoint [7] 372108 0
Measured every 2 h throughout the 14 h conditions
Secondary outcome [8] 372109 0
Substrate utilisation measured from expired oxygen and carbon dioxide levels (indirect calorimetry)
Timepoint [8] 372109 0
Measured at 11 time points over 24 hours; specifically, at ~7:40 am, ~8:40 am, ~9:50 am, ~10:40 am, ~1:45 pm, ~2:40 pm, ~5:45 pm, ~6:40 pm, ~7:50 pm, ~8:40 pm and the next day at ~7:40 am.
Secondary outcome [9] 372180 0
Measures of glycaemic variability from the continuous glucose monitor data
Timepoint [9] 372180 0
Measured over 24 hours in each condition from the continuous glucose monitor data

Eligibility
Key inclusion criteria
• Aged 35 to 65 years old
• Diagnosed (by a GP/endocrinologist) with type 2 diabetes mellitus (T2D), with an HbA1c between 6.5% - 9.9%, and either diet-controlled or taking a maximum of two oral antihyperglycemic agents (excluding sulphonylureas, insulin and GLP-1 agonists)
• Body mass index (BMI) between 25 - 45 kg/m2 (but total mass not >200 kg due to DXA measures)
Minimum age
35 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Meeting current guidelines for physical activity (i.e. greater than 150 minutes of moderate physical activity per week for greater than 4 weeks);
• Taking glucose lowering medications which recommend not fasting (i.e. sulphonylureas, or insulin) or requiring injecting (i.e. GLP-1 agonists);
• Currently following a strict diet (i.e. vegan, coeliac/gluten free, ketogenic);
• Participate in regular fasting (defined as fasting for equal to or greater than 16 h per day or having completed twelve 24-h fasts within the past year);
• Participating in shift work (i.e. greater than 3 h between 10 pm and 5 am for 1 day per week (more than 50 days per year))
• Not weight stable (greater than 5 kg change over last 3 months);
• On prescribed medications required to be taken with food in the early morning or late evening or taking other prescribed medications for greater than 3 months;
• Current smoker (tobacco, nicotine or marijuana) or within 3 months of quitting;
• Women who are pregnant, breastfeeding (within 24 wk);
• Psychopharmacological treatment that has not been stable for more than 3 months;
• Medications known to promote weight gain, weight loss or interact with glucose metabolism (i.e. corticosteroids);
• Diagnosed gastrointestinal conditions, surgery (i.e. bariatric) or impaired nutrient absorption;
• Known physical activity contraindications;
• Major illness/physical problems (acute or chronic) that may limit the ability to perform walking on a treadmill for 15 minutes;
• Previous hospitalisation/treatment for cardiac event.

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)
Completed by an independent researcher using sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Blocked randomisation using a randomisation table created by computer software (i.e. computerised sequence generation), in block sizes of 4-8.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis
Following recent recommendations on data analysis of cross-over trials (Kenward and Roger, 2010), linear mixed models with random intercepts will be used to evaluate the differential effects of the experimental conditions on the selected outcomes. Models will be adjusted for potential confounding variables and marginal means with 95% confidence intervals will be calculated. A probability level of 0.05 will be adopted.

Power calculations
Power calculations will be made in relation to the primary outcome of glucose AUC from continuous glucose monitoring. Based on data from Dempsey et al, (Diabetologia, 2017), we estimate that the effect size (Cohen’s d for repeated measures) of an acute one-day exposure to the exericse + control (group #3), relative to control (Group #4), would be 1.8 (very large) for glucose AUC. Sample size calculation indicates that n=5 participants would be required to detect an effect size of 1.8 with a power of 0.80 and a of 0.05. Due to the multiple comparisons, and to account for an expected 15-20% attrition, we will aim to recruit 20 participants for 16 to complete the intervention.


Recruitment
Recruitment status
Recruiting
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] 26926 0
3065 - Fitzroy

Funding & Sponsors
Funding source category [1] 303161 0
University
Name [1] 303161 0
Australian Catholic University
Address [1] 303161 0
Locked Bag 4115
Fitzroy 3065 VIC
Country [1] 303161 0
Australia
Primary sponsor type
Individual
Name
Dr Evelyn Parr
Address
Exercise and Nutrition Research Program
Mary MacKillop Institute for Health Research
Level 5, 215 Spring Street
Melbourne 3000 VIC
Country
Australia
Secondary sponsor category [1] 303176 0
None
Name [1] 303176 0
Address [1] 303176 0
Country [1] 303176 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303723 0
Australian Catholic University Human Research Ethics Committee
Ethics committee address [1] 303723 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] 303723 0
Australia
Date submitted for ethics approval [1] 303723 0
21/03/2019
Approval date [1] 303723 0
21/06/2019
Ethics approval number [1] 303723 0
2019-61HC

Summary
Brief summary
Newly diagnosed individuals with T2D can be managed primarily by alterations to diet and physical activity (exercise) patterns, which are used to help control blood glucose. However, uptake and adherence to any behaviour change strategy is typically challenging and therefore low. Recently, time-restricted eating (TRE) has emerged as a promising therapeutic strategy that allows meals to be consumed alongside societal norms. Rather than stipulating the composition of meals, TRE aims to reduce the ‘eating window’ to facilitate a longer overnight fast (i.e. eating between 10 am-6 pm, rather than over periods longer than 12 h). Via TRE, meal timing can be aligned with the biological circadian rhythm. Specifically, an earlier dinner may contribute to better glucose control due to the known deterioration of the hormone insulin to regulate glucose declining over the day. In those with T2D, a later breakfast may also be beneficial to avoid eating at the same time as the morning spike in fasting glucose, which is known as the ‘dawn phenomenon’ in individuals with T2D and coincides with the increased circadian concentrations of cortisol, known to stimulate the liver to release glucose into the circulation. Acutely, to our knowledge, TRE has not been measured in individuals with type 2 diabetes.
TRE performed over a period of weeks has been shown to effectively reduce post-meal insulin, blood pressure, and evening appetite; if continued for up to one year it has been demonstrated to result in sustained weight loss. However, there are a lack of studies investigating the acute, one-day effects of TRE, particularly in the context of other behaviours that might influence circadian rhythm. Exercise, for example, is a potent stimulus known to influence both circadian rhythm and glucose control. For individuals with T2D, just 10 minutes of walking in each of the 1 hour post-prandial period across a day is enough to improve blood glucose control. However, it is unknown whether strategically-timed exercise combined with TRE would result in an additive benefit to glucose control over the course of a day. In addition, it is unknown whether the benefits of exercise for glucose control would mitigate the detrimental effect of an extended feeding window on glucose control.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 94574 0
Dr Evelyn Parr
Address 94574 0
Exercise and Nutrition Research Program
Mary MacKillop Institute for Health Research
Level 5, 215 Spring Street
Melbourne 3000 VIC
Country 94574 0
Australia
Phone 94574 0
+61 392308278
Fax 94574 0
Email 94574 0
evelyn.parr@acu.edu.au
Contact person for public queries
Name 94575 0
Dr Evelyn Parr
Address 94575 0
Exercise and Nutrition Research Program
Mary MacKillop Institute for Health Research
Level 5, 215 Spring Street
Melbourne 3000 VIC
Country 94575 0
Australia
Phone 94575 0
+61 392308278
Fax 94575 0
Email 94575 0
evelyn.parr@acu.edu.au
Contact person for scientific queries
Name 94576 0
Dr Evelyn Parr
Address 94576 0
Exercise and Nutrition Research Program
Mary MacKillop Institute for Health Research
Level 5, 215 Spring Street
Melbourne 3000 VIC
Country 94576 0
Australia
Phone 94576 0
+61 392308278
Fax 94576 0
Email 94576 0
evelyn.parr@acu.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Potentially identifiable information.
What supporting documents are/will be available?
No other documents available
Summary results
No Results