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Trial registered on ANZCTR


Registration number
ACTRN12617000392369
Ethics application status
Approved
Date submitted
14/03/2017
Date registered
16/03/2017
Date last updated
21/05/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Mitigating the effects of sitting on vascular dysfunction in type 2 diabetes: the MOVE trial
Scientific title
Interrupting prolonged sitting to mitigate the effects of vascular endothelial dysfunction in patients with type 2 diabetes
Secondary ID [1] 291449 0
Nil known
Universal Trial Number (UTN)
Trial acronym
MOVE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Endothelial Function 302482 0
Type 2 Diabetes 302483 0
Condition category
Condition code
Cardiovascular 302042 302042 0 0
Other cardiovascular diseases
Metabolic and Endocrine 302043 302043 0 0
Diabetes
Diet and Nutrition 302064 302064 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This randomised crossover trial in overweight or obese adults diagnosed with type 2 diabetes will involve three acute experimental conditions (each of 8 hours duration; 1 hour to achieve steady state and a 7 hour experimental period beginning when breakfast is served) to examine the impact of prolonged uninterrupted sitting, or breaking up sitting with brief bouts of simple resistance activities on endothelial function. Twenty four inactive and injury-free participants aged between 35-70 years will be recruited. Participants will visit the Physical Activity Laboratory at the Baker Heart and Diabetes Institute on 4 separate occasions.
Participants will initially be screened for eligibility via a telephone-administered interview, with likely candidates invited to attend a medical screening & familiarisation at the Baker. During the visit participants will be able to ask further questions prior to giving signed consent to participate. The medical screening will consist of a medical examination by the study physician, resting 12 lead electrocardiogram and a point-of-care HbA1c test (finger prick) to determine eligibility immediately. After eligibility has been confirmed, participants will proceed to the familiarisation part of visit 1. In order to ensure optimal safety and to allow orientation with the testing procedures and measurement devices, the study staff will familiarize participants with simple resistance activities, ensuring they are comfortable with the exercises and suitable technique and movement consistency are achieved. Anthropometric measurements (weight, height and waist circumference) will be obtained and participants will be shown the FMD procedure.
Participants will be instructed not to alter their habitual pattern of daily activities while involved in the trial. To minimise any potential diet-induced variability in the metabolic profile, participants will be provided with a standard ‘food pack’, containing a dinner meal for the night prior to each experimental condition, and dinner and breakfast following the experimental condition. All food packs will be matched or macronutrient composition (as % of total energy intake, with a macronutrient profile of 53-55% energy from carbohydrate, 12-15% energy from protein, and 30-33% energy from fat). Participants will be instructed to consume only the food items within the food pack for the dinner meal prior to the experimental condition, between 7-9pm that evening, and to then fast until the trial condition the next morning. They will also be asked to record their food and fluid intake in a food diary and to avoid and moderate and/or vigorous intensity activity for at least 72 hours prior to each experimental condition. To assess compliance and habitual physical activity, participants will be fitted with two objective activity monitors at the familiarisation session – an accelerometer (Actigraph model GT3X+) worn on the wrist, and an inclinometer (activPAL3TM) worn on the thigh, which will be worn for the week prior to each condition. The objective activity monitoring will be used in combination with an activity diary. At this visit participants will also be fitted with an Abbott Freestyle Libre Flash Glucose Monitoring system (Abbott Diabetes Care, Australia) with a sensor worn on the back of the upper arm. Flash glucose monitoring involves scanning the sensor with a reader device to upload glucose data approximately 4 times daily, with no need for finger prick calibrations. Participants will wear this system for the duration of the study, with a new sensor fitted at the beginning of the second experimental visit.
Each participant will then complete three experimental conditions in a laboratory setting, supervised by the study staff to ensure adherence to the experimental conditions. The three conditions will be separated by a minimum 6-day washout period to account for any residual physiological effects of the intervention. Participants will be advised to wear appropriate footwear and clothing to allow sufficient range of motion at the knee and hip (45 degrees to 90 degrees for half-squats or knee raises). In all experimental conditions participants will be seated in a comfortable lounge-chair and have access to a television, DVD player and reading materials such as newspapers and magazines. They will be instructed to minimise excessive movement, but will be allowed to visit the toilet (via wheelchair) when necessary.
Before starting the experimental conditions, participants will sit for the first hour, during which baseline blood pressure measurements will be taken. An in-dwelling venous cannula will be inserted, and a baseline blood sample drawn. Participants will be then given a standardised breakfast meal comprised of 33% of estimated daily energy requirements, with a macronutrient profile of 53-55% energy from carbohydrate, 12-15% energy from protein, and 30-33% energy from fat and the activity protocols begin.
The two activity interventions are;
A) Simple Resistance Exercises and Interrupted Sitting (30): Participants will complete a 3 min bout of simple resistance activities every 30 minutes, remaining seated at all other times (except for toilet breaks). The activities will be allocated into nine 20 second segments, alternating between body weight half squats, calf raises and brief gluteal contractions in-between single leg knee raises (total exercise time equals to 36 mins). This interchange between movements will provide rest for the corresponding muscle groups between each activity segment. To ensure appropriate standardisation, participants will complete each activity in a controlled manner within their range of motion (knee or hip 45 to 90 degrees for half-squats or knee raises), while synchronizing the tempo of each activity to a demonstration video playing.
B) Simple Resistance Exercises and Interrupted Sitting (60): As for condition A, except participants complete a 6 minute bout of simple resistance activities every 60 minutes throughout the 7 hour experimental period. This procedure will be completed on 6 occasions, totalling 36 minutes of activity. The simple resistance activities will follow exactly the same procedure as condition A, except each bout will last for 6 min.
Before leaving the laboratory on the experimental days, participants will be fitted with a 24 hour ambulatory blood pressure monitor (ABPM) to be worn until noon the following day in addition to the Libre. Participants will be asked to keep these devices on overnight after each trial to assess what happens to their blood glucose and blood pressure during this period. After the final study visit, the participant will remove both devices and mail back to the Baker in a provided parcel post bag.
Intervention code [1] 297491 0
Treatment: Other
Intervention code [2] 297492 0
Lifestyle
Comparator / control treatment
One day of prolonged sitting without activity breaks. Participants will sit quietly in a comfortable chair for an 8 hour period.
Control group
Active

Outcomes
Primary outcome [1] 301461 0
Endothelial function of femoral artery using high-resolution Doppler ultrasound.
Timepoint [1] 301461 0
On the trial days, assessed at baseline, 1, 3.5, 4.5 and 7 hours.
Secondary outcome [1] 332731 0
Postprandial glucose response from the venous blood and Flash Glucose Monitoring Sytem (Libre)
Timepoint [1] 332731 0
Venous blood samples collected every 30 minutes during the experimental condition. Glucose data from the Flash Glucose Monitoring System from familiarisation visit to the day after the final experimental visit.
Secondary outcome [2] 332732 0
Blood Pressure will be measured using an OMROM HEM-907 automatic digital blood pressure machine..
Timepoint [2] 332732 0
Measured at baseline, 0.5, 1.5, 2.5, 3.5, 4.5, 5.5, and 6.5 hours during each experimental condition.
Secondary outcome [3] 332733 0
Blood Pressure using 24 hour Ambulatory Blood Pressure Monitor
Timepoint [3] 332733 0
Measures blood pressure every 20 minutes during the day and every 30 minutes over night for the 24 hour period following each experimental condition.
Secondary outcome [4] 332734 0
Postprandial insulin response measured from the venous blood
Timepoint [4] 332734 0
Venous blood samples collected every 30 minutes during the experimental condition
Secondary outcome [5] 332735 0
A composite secondary outcome consisting of vasoconstrictive metabolites {Endothelin -1}, Catecholamines and inflammatory biomarkers {RNase Protection Assay, Inter-Cellular Adhesion Molecules (ICAMs), Vascular Cell Adhesion Molecules (VCAMs) and lipidomics} from the venous blood samples.
Timepoint [5] 332735 0
Venous blood samples collected every 30 minutes during the experimental condition
Secondary outcome [6] 332826 0
Postprandial triglyceride response measured from the venous blood
Timepoint [6] 332826 0
Venous blood samples collected every 30 minutes during the experimental condition

Eligibility
Key inclusion criteria
Overweight and obese participants aged between 35-70 years will be recruited from the local community. Eligibility will be based on having a BMI greater than or equal to 25 but less than 40 kg/m2, diagnosed with Type 2 diabetes for at least 3 months or more, controlled with a maximum of three anti hyperglycemic agents, and must be English speaking.
Minimum age
35 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria include HbA1c <6.5% or >10%, taking insulin, pregnancy, current smoker, self-reported sitting of < 5 h per day (i.e employment in a non-sedentary occupation), regularly engaging in moderate intensity physical activity for greater than or equal to 150 min per week or vigorous intensity physical activity greater than or equal to 75 min per week for > 3 months, and any known physical activity contraindications or major illness/physical problems (acute or chronic) that may limit participation in activity.

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)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised sequence generation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
A sample size of 24 individuals (15% attrition) would provide >90% power, assuming two-tailed alpha=0.05 and a standard deviation of 1% between individuals, to detect a change in FMD of 1% between the sitting and activity conditions. A 1% difference in FMD is associated with clinically meaningful ~7% difference in cardiovascular events.
Generalized linear mixed models with random intercepts will be used to evaluate the differential effects of the experimental conditions on the outcomes, adjusted for potential period effects and period-dependent confounders. Use of generalised linear mixed models allows for missing data points. All statistical analyses will be performed using Stata for Windows, version 14.1 or higher.

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

Funding & Sponsors
Funding source category [1] 295915 0
Charities/Societies/Foundations
Name [1] 295915 0
Heart Foundation
Address [1] 295915 0
Level 12, 500 Collins Street
Melbourne VIC 9000
Country [1] 295915 0
Australia
Primary sponsor type
Individual
Name
Professor David Dunstan
Address
Physical Activity Laboratory
Baker Heart and Diabetes Institute
Level 4, Alfred Centre
99 Commercial Road
Melbourne VIC 3004
Country
Australia
Secondary sponsor category [1] 294789 0
None
Name [1] 294789 0
Address [1] 294789 0
Country [1] 294789 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297196 0
Alfred Health Human Ethics Committee
Ethics committee address [1] 297196 0
Office of Ethics and Research Governance
Ground Floor, Linay Pavillion,
The Alfred Hospital,
55 Commercial Road
Melbourne VIC 3004
Ethics committee country [1] 297196 0
Australia
Date submitted for ethics approval [1] 297196 0
01/02/2017
Approval date [1] 297196 0
28/03/2017
Ethics approval number [1] 297196 0
50/17

Summary
Brief summary
The primary aim of this study is to characterise the effects of prolonged sitting on femoral artery endothelial function in patients with type 2 diabetes and to investigate the potentially beneficial effects of (i) 3 min every 30 min; and (ii) 6 min every 60 min of simple resistance activity (SRA) breaks on endothelial function, and postprandial glucose, insulin and lipid profiles in comparison to prolonged sitting. Secondary outcome measures will also provide information on the potential signalling pathways (insulin and SNS-mediated vasoconstriction pathways) that are contributing to the decline in vascular function with prolonged sitting.
For this, we propose to undertake a randomised crossover trial in twenty four inactive and injury-free overweight/obese adults aged between 35-70 years diagnosed with type 2 diabetes. This study will involve three acute experimental conditions (each of 8 hours duration), separated by a minimum 6-day washout period to account for any residual physiological effects of the intervention. Each participant will complete three conditions, involving (i) Uninterrupted Sitting - 8 hours of prolonged sitting; (ii) Simple Resistance Exercises (30) + Interrupted Sitting: 8 hours of sitting with 3 minutes of simple resistance activity breaks every 30 minutes; and (iii) Simple Resistance Exercises (60) + Interrupted Sitting: 8 hours of sitting with 6 minutes of simple resistance activity breaks every 60 minutes. Standardised breakfast and lunch will be provided for the test. Dinner will also be provided prior to each condition, and dinner and breakfast will be provided following each condition.
Vascular function will be directly measured using Flow Mediated Dilation (FMD). FMD is a widely-used non-invasive method to describe endothelial function and vasodilation of an artery following ischaemia. Participants will be fitted with a flash glucose monitoring system (Libre) to wear from the first visit to the day after the final study visit. During the experimental conditions, venous blood samples will be collected every 30 minutes and blood markers of endothelial function will also be measured, including endothelin-1 production. Changes in Sympathetic Nervous System (SNS) activity may help to explain any differences in FMD over the day and between conditions. SNS activity will be indirectly measured via catecholamine levels in the blood. Plasma markers of cardiovascular health and inflammation will also be measured, as well as blood pressure (during experimental sessions). At the conclusion of each condition, participants will be fitted with a 24 hour ambulatory blood pressure monitor (ABPM).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 73306 0
Prof David Dunstan
Address 73306 0
Physical Activity Laboratory
Baker Heart and Diabetes Institute
Level 4, Alfred Centre
99 Commercial Road
Melbourne VIC 3004
Country 73306 0
Australia
Phone 73306 0
+61 3 8532 1873
Fax 73306 0
Email 73306 0
David.Dunstan@baker.edu.au
Contact person for public queries
Name 73307 0
Ms Ashleigh Homer
Address 73307 0
Physical Activity Laboratory
Baker Heart and Diabetes Institute
Level 4, Alfred Centre
99 Commercial Road
Melbourne VIC 3004
Country 73307 0
Australia
Phone 73307 0
+61 3 8532 1786
Fax 73307 0
Email 73307 0
Ashleigh.Homer@baker.edu.au
Contact person for scientific queries
Name 73308 0
Ms Ashleigh Homer
Address 73308 0
Physical Activity Laboratory
Baker Heart and Diabetes Institute
Level 4, Alfred Centre
99 Commercial Road
Melbourne VIC 3004
Country 73308 0
Australia
Phone 73308 0
+61 3 8532 1786
Fax 73308 0
Email 73308 0
Ashleigh.Homer@baker.edu.au

No data has been provided for results reporting
Summary results
Not applicable