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Trial registered on ANZCTR


Registration number
ACTRN12616000578404
Ethics application status
Approved
Date submitted
27/04/2016
Date registered
4/05/2016
Date last updated
4/05/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Effects of Reducing Prolonged Sitting on the Endothelial Function in Overweight/Obese Adults
Scientific title
Effects of Reducing prolonged sitting on the Endothelial function in overweight/obese adults : The REDUCE Study
Secondary ID [1] 288894 0
nil
Universal Trial Number (UTN)
Trial acronym
The REDUCE Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Endothelial function 298225 0
Condition category
Condition code
Cardiovascular 298358 298358 0 0
Normal development and function of the cardiovascular system
Metabolic and Endocrine 298359 298359 0 0
Normal metabolism and endocrine development and function
Neurological 298360 298360 0 0
Studies of the normal brain and nervous system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This randomised crossover trial in overweight or obese adults will involve two acute experimental conditions (each of 6 hours duration), to examine the impact of prolonged uninterrupted sitting, or breaking up sitting with brief bouts of simple resistance activities (3 minutes every 30 minutes) on endothelial function. Twenty five inactive and injury-free participants aged between 35-75 years will be recruited. Participants will visit the Physical Activity Laboratory at Baker IDI on 3 separate occasions.
Participants will first attend a familiarisation session 3-7 days prior to the commencement of the experimental trial, in order to ensure optimal safety and to allow orientation with the testing procedures and measurement devices. During this visit, 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 also be obtained. Activity intensity levels will be monitored and assessed using heart-rate monitoring, and the Borg rate of perceived exertion scale (RPE – numbered scale from 6-20) and visual analogue scales (VAS – continuous scale from ‘extremely easy’ to ‘extremely difficult’).
Each participant will then complete two experimental conditions in a laboratory setting, supervised by the study staff to ensure adherence to the experimental conditions. The two conditions will be separated by a minimum 5-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 when necessary.
Before starting the experimental conditions, participants will sit for the first one hour, during which baseline measurements will be taken. Participants will be then given a standardised breakfast meal of croissant with ham & cheese, Pine and mango juice with a choice of Corn flakes or Sultana bran (with Milk). This will comprise 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.
The two experimental conditions are-
1) Uninterrupted Sitting (control condition): Participants will sit quietly for 5 hours.
2) Simple Resistance Exercises and Interrupted Sitting: Identical procedure to Condition 1, however, participants will complete a 3 min bout of simple resistance activities every 30 minutes. 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 27 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.
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, as well as lunch and dinner following each condition. All food packs will be matched for 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 each meal. The lunch (based on 27 % estimated energy requirements-consisting of bread roll with a choice of Turkey/Cheese/Cranberry/Lettuce roll or Ham/Cheese/Cranberry/Lettuce roll or Turkey/Cheese/Mayonnaise/Lettuce roll or Ham/Cheese/Mayonnaise/Lettuce roll with a choice of Lemonade or Fanta) will be consumed before leaving the laboratory, and the dinner meals (based on 40% estimated energy requirements-consisting of Mongolian beef, apricot muesli bar and roasted cashews) between 7-9pm in the evening. Participants will be instructed to only consume the food contained in the packs, and to perform their habitual pattern of daily activities for the next 24 hours. The meals will be self-selected from pre-selected options and will be the same meal for both conditions.

Before leaving the laboratory on the experimental days, participants will be fitted with both a 24 hour ambulatory blood pressure monitor (ABPM) and a continuous glucose monitoring system (CGMS). 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. This will require them to take 3 blood samples with a finger prick blood taking device provided by the research staff. The next morning before breakfast participants will simply remove both devices (tape and all), put in a pre-prepared envelope and mail it back to Baker IDI (unless collected by researchers).
Intervention code [1] 294352 0
Lifestyle
Comparator / control treatment
One day of prolonged sitting without activity breaks: Participants will sit
quietly in a comfortable chair for a 6 hour period
Control group
Active

Outcomes
Primary outcome [1] 297835 0
Endothelial function of superficial femoral artery using high-resolution Doppler ultrasound.
Timepoint [1] 297835 0
On the trial days, assessed at baseline, 0.5, 1.5, 2.5, 3.5 and 4.5 hours for the superficial femoral artery
Primary outcome [2] 298164 0
Endothelial function of brachial artery using high-resolution Doppler ultrasound.
Timepoint [2] 298164 0
On the trial days, assessed at baseline and 5 hours for the brachial artery.
Secondary outcome [1] 322867 0
Post prandial insulin response from the venous blood samples
Timepoint [1] 322867 0
Blood samples collected every 30 minutes during the experimental condition
Secondary outcome [2] 322868 0
Sympathetic nervous system activity measured using microneurography
Timepoint [2] 322868 0
At the end of the trial condition on the experimental days
Secondary outcome [3] 322869 0
A composite secondary outcome consisting of vasoactive metabolites {Endothelin -1 and Nitrate/nitrite} and inflammatory biomarkers {ELISA Assay, Intercellular Adhesion Molecules (ICAMs) and Vascular Cell Adhesion Molecules (VCAMs)} from the venous blood samples
Timepoint [3] 322869 0
Blood samples collected at baseline, 0.5, 2 and 5 hours
Secondary outcome [4] 322870 0
Postprandial glucose response from the venous blood and Continuous Glucose Monitoring System (CGMS)
Timepoint [4] 322870 0
Venous blood samples collected every 30 minutes during the experimental condition and CGMS for 24 hours after each experimental condition.
Secondary outcome [5] 322871 0
Blood Pressure using 24 hour Ambulatory Blood Pressure Monitor
Timepoint [5] 322871 0
for the 24 hour period following each experimental condition
Secondary outcome [6] 322872 0
Spontaneous baroreflex responses will be assessed using ECG and a beat-to-beat blood pressure monitors
Timepoint [6] 322872 0
assessed continuously during the experimental conditions

Eligibility
Key inclusion criteria
Overweight and obese participants aged between 35-75 years will be recruited from the local community. Eligibility will be based on having a BMI more than or equal to 25 but less than 40 kg/m2, and English speaking.
Minimum age
35 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria include pregnancy, employment in a non-sedentary occupation i.e. less than 5 hours sitting per day, regularly engaged in moderate-intensity exercise more than or equal to 150 min per week for more than 3 months, diagnosed diabetes, use of glucose/lipid lowering/antidepressant medications, current smoker, pre-menopausal or menopausal women, known physical activity contraindications, major illness/physical problems (acute or chronic) that may limit their ability to perform the activity bouts

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)
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
Power calculations have been made in relation to the primary outcome measure of FMD and reflect the cross-over design of the study. Based on our pilot data and previous publications, we have estimated that a final sample size of 20 will be sufficient to detect previously-observed effects sizes =0.481 ( partial eta squared ) for the significant reduction in primary outcome of FMD across time with a minimum power of 80% and a probability of 0.05 (2-tailed test). As a safeguard, and using our experience from clinical trials and behavioural interventions, we will over-sample to cover a conservatively estimated attrition rate of 25%. Thus, 25 participants will be recruited.

Generalized linear mixed models (GLMMs) with random intercepts will be used to evaluate the differential effects of the experimental conditions on the outcomes. All models will include a binary variable indicating the experimental condition (intervention vs. control), adjusted for potential period effects and period-dependent confounders (baseline values for the outcome of interest, dietary intake and physical activity). Given that the study will use a balanced orthogonal design and substantial imbalances due to dropout are unlikely, it will not be necessary to adjust for subject-level covariates (e.g., age). GLMMs are appropriate for correlated data (repeated measures) with various distributional assumptions and can easily accommodate missing data. A probability level of 0.05 will be adopted. All statistical analyses will be performed with Stata 14 (StataCorp LP).

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] 293249 0
Government body
Name [1] 293249 0
National Health and Medical Research Council (NHMRC)
Address [1] 293249 0
Level 1

16 Marcus Clarke Street

Canberra ACT 2601
Country [1] 293249 0
Australia
Primary sponsor type
Individual
Name
Professor David Dunstan
Address
Physical Activity Laboratory
Baker IDI Heart and Diabetes Institute
Level 4, Alfred Centre
99 Commercial Road
Melbourne VIC 3004
Country
Australia
Secondary sponsor category [1] 292186 0
None
Name [1] 292186 0
Address [1] 292186 0
Country [1] 292186 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294727 0
Alfred Health Human Ethics Committee
Ethics committee address [1] 294727 0
OFFICE OF ETHICS & RESEARCH GOVERNANCE -
Ground Floor, Linay Pavilion,
The Alfred Hospital,
55 Commercial Road, Melbourne,
Victoria 3004, Australia
Ethics committee country [1] 294727 0
Australia
Date submitted for ethics approval [1] 294727 0
Approval date [1] 294727 0
26/02/2016
Ethics approval number [1] 294727 0

Summary
Brief summary
The primary aim of this study is to determine whether short activity breaks incorporating upright simple resistance activities can improve blood vessel (endothelial) function compared to 5 hours of prolonged, uninterrupted 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 five inactive and injury-free overweight/obese adults aged between 35-75 years. This study will involve two acute experimental conditions (each of 6 hours duration), separated by a minimum 5-day washout period to account for any residual physiological effects of the intervention. Each participant will complete two conditions, involving (i)Uninterrupted Sitting - 5 hours of prolonged sitting; and (ii) Simple Resistance Exercises + Interrupted Sitting: 5 hours of sitting with 3 minutes of simple resistance activity breaks every 30 minutes. Standardised breakfast will be provided for the test. Lunch and dinner will also 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. Venous blood samples will be collected every 30 minutes and blood markers of endothelial function will also be measured, including nitric oxide and 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; and directly measured using microneurography, where a microelectrode will be inserted under the skin to sit on top of the peroneal nerve (behind the knee) and record electrical activity. The SNS also helps to mediate the baroreflex, which regulates acute blood pressure changes by controlling heart rate, contractility and peripheral artery resistance. Spontaneous baroreflex responses will be assessed using ECG and a beat-to-beat finger BP cuff. Plasma markers of cardiovascular health and inflammation will also be measured. At the conclusion of each condition, participants will be fitted with both a 24 hour ambulatory blood pressure monitor (ABPM) and a continuous glucose monitoring system (CGMS).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 64818 0
Prof David Dunstan
Address 64818 0
Physical Activity Laboratory
Baker IDI Heart and Diabetes Institute
Level 4, Alfred Centre
99 Commercial Road
Melbourne VIC 3004
Country 64818 0
Australia
Phone 64818 0
+61 3 8532 1873
Fax 64818 0
+61 3 8532 1100
Email 64818 0
David.Dunstan@bakeridi.edu.au
Contact person for public queries
Name 64819 0
Dr Megan Grace
Address 64819 0
Physical Activity Laboratory
Baker IDI Heart and Diabetes Institute
Level 4, Alfred Centre
99 Commercial Road
Melbourne VIC 3004
Country 64819 0
Australia
Phone 64819 0
+61 3 8532 1855
Fax 64819 0
+61 3 8532 1100
Email 64819 0
megan.grace@bakeridi.edu.au
Contact person for scientific queries
Name 64820 0
Dr Megan Grace
Address 64820 0
Physical Activity Laboratory
Baker IDI Heart and Diabetes Institute
Level 4, Alfred Centre
99 Commercial Road
Melbourne VIC 3004
Country 64820 0
Australia
Phone 64820 0
+61 3 8532 1855
Fax 64820 0
+61 3 8532 1100
Email 64820 0
megan.grace@bakeridi.edu.au

No information has been provided regarding IPD availability
Summary results
No Results