Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12613001037796
Ethics application status
Approved
Date submitted
13/09/2013
Date registered
18/09/2013
Date last updated
26/07/2019
Date data sharing statement initially provided
26/07/2019
Date results provided
26/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of exercise intensity on cardiac and vascular function, and intra-abdominal fat in obese children and adolescents.
Scientific title
Effect of exercise intensity on cardiac and vascular function, and intra-abdominal fat in obese children and adolescents.
Secondary ID [1] 283194 0
Nil
Universal Trial Number (UTN)
U1111-1147-9048
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obesity and overweight in children and adolescents 290059 0
Condition category
Condition code
Diet and Nutrition 290434 290434 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Eligible participants are randomized to the three arms of the study: a high intensity interval training group, a moderate intensity exercise group and a control group. Participants in all three interventions and their general practitioners are given results from study examinations after each testing session (at baseline, 3 months and 12 months).

The exercise intervention arms combine dietary advice with an exercise training intervention over 12 months. Participants assigned to these arms will receive dietary education sessions that will parallel sessions provided to those assigned to the control group. They will attend a 30 minutes session every second week for three months, followed by one session every two months for the next nine months.

Participants in the exercise groups will be asked to train three times a week for twelve months. In the first three months, they will perform two supervised sessions in the gymnasium in the School of Human Movement Studies, UQ St Lucia. The remaining one session will be performed at home. During the following nine months, all exercising training will be performed at home.

The exercise training in both groups will be by walking or running on a treadmill, or on a bike for the older children. The younger children will have an exercise activity adjusted to age, gender and climate (to be discussed with clinical investigators). Each session, participants will be given the choice of using a treadmill or stationary bike.

All participants will perform a 10-minute warm up at 60% of maximal heart rate (HRmax).

Participants randomised to the high intensity interval training (HIIT) group will either walk, run or cycle at 85-95% of their maximal heart rate at intervals of 4 x 4 minutes, with 3 minute active breaks (~60% of HRmax) between intervals. Total exercise time in this group will be 40 minutes.

Participants randomised to the moderate intensity exercise (MICT) group will walk, run or cycle continuously at 70% HRmax for approximately 44 minutes to equalize the energy expenditure performed by the HIIT. Total exercise time in this group will be 50 minutes.

All participants will perform a 5-minute cool down period.

Participants will be encouraged to maintain the required HR through a reward system. For example, the younger children (7-12) will get stars/stickers on a public board, giving them feedback on their progress compared to others in the study. Participants will be required to fill out a training diary to record the one unsupervised session every week that they do. An compliance of 80% to training sessions will be required.
Intervention code [1] 287922 0
Lifestyle
Comparator / control treatment
The control group will receive dietary education sessions. Participants assigned to this group are asked to attend ten 30-minute individual diet intervention sessions over the twelve months. They will attend a session every second week for three months, followed by one session every two months for the next nine months. Assessment will occur at three months and twelve months.

Healthy eating education sessions will be led by a dietitian following recent dietary guidelines (NHRMC 2013). Emphasis of the sessions will be on portion sizes and regular meal times. The dietitian will be blinded to allocation of participants.
Control group
Active

Outcomes
Primary outcome [1] 290457 0
Myocardial function assessed by a full resting echocardiogram and an exercise echocardiogram.

LV standard Doppler echocardiographic indices will be measured and body surface area (m2) will be used to normalize cardiac dimensions for differences in body size. Mitral annulus excursion (MAE, mm), pulsed wave tissue Doppler velocities; peak systolic (S’), peak early diastolic (E’) and peak late diastolic (A’) will be measured at the AV-plane level in 4-chamber and 2-chamber view and a mean of the 4 points will be used. Right ventricle function standard Doppler echocardiographic indices will be measured and TAPSE, S’, E’, A’. Deformation (strain) and deformation rate (strain rate) will also be analyzed.

Peak systolic (S’) tissue velocity will be the primary outcome measure with the other measures of myocardial structure and function used for the secondary objectives.

An exercise echocardiogram will performed to assess the heart's response to exercise on a cycle ergometer. After the resting echocardiogram images have been obtained, the individuals will exercise on a stationary cycle ergometer in upright position starting at 25 W with 25 W increments every 3 minutes until they have attained their maximum heart rate. Recordings will be done at baseline and at peak assessing apical 4-chamber and 2-chamber in B-mode and tissue Doppler. ECG and blood pressure will be monitored during the test.
Timepoint [1] 290457 0
Outcome will be measured at baseline, following 3 month intervention, and after 9 month follow up (12 months after starting study)
Primary outcome [2] 290458 0
Intra-abdominal fat will be measured using magnetic resonance imaging (MRI). Subjects will be positioned supine inside the bore of the magnet. A single slice at the level on the umbilicus will be used for analysis and calculation of the visceral fat and subcutaneous fat areas. A single trained investigator blinded to subject allocation will analyse each of the MRI images in a random order.
Timepoint [2] 290458 0
Outcome will be measured at baseline, following 3 month intervention, and after 9 month follow up (12 months after starting study)
Primary outcome [3] 290459 0
Arterial endothelial- dependent dilatation will be measured as flow-mediated dilatation (FMD) using high-resolution vascular ultrasound. The procedure requires a blood pressure cuff to be inflated around the participants forearm for 5 minutes. This will partially occlude blood flow to the hand. After 5 minutes the cuff will be released and the probe is placed against the forearm to measure the change in the diameter of the artery as the blood flow returns to normal, as method known as flow-mediated dilatation (FMD).
Timepoint [3] 290459 0
Outcome will be measured at baseline, following 3 month intervention, and after 9 month follow up (12 months after starting study)
Secondary outcome [1] 304550 0
Arterial stiffness will be assessed by measuring pulse wave velocity and pulse wave analysis using a SpygmoCor machine. The participants will be asked to lie down quietly for 15 minutes. Following this, pulse wave analysis and pulse wave velocity will be taken.
Timepoint [1] 304550 0
Outcome will be measured at baseline, following 3 month intervention, and after 9 month follow up (12 months after starting study)
Secondary outcome [2] 304551 0
VO2max will be measured during uphill treadmill walking or running, using ergospirometry. A warm-up period for 10 min (~60% of HRmax) will precede the test. A standardised Bruce protocol will be used for all participants. A levelling off of oxygen uptake (VO2) despite increased workload and respiratory exchange ratio =1.05 will be used as criteria for VO2max. Heart rate will be measured continuously during the test and specifically noted at 1 minute, 3 minutes and 5 minutes following the completion of exercise to determine heart rate recovery. Peak exercise blood pressure will also be measured.
Timepoint [2] 304551 0
Outcome will be measured at baseline, following 3 month intervention, and after 9 month follow up (12 months after starting study)
Secondary outcome [3] 304552 0
Dual-energy x-ray absorptiometry (DXA) will be used to determine body composition (fat and fat –free mass) as well as bone mineral density. This will require the participant to lie still while an x-ray of their entire body is taken using the DXA machine. This process will take about 7 minutes. DXA is able to measure total body composition and fat content with a high degree of accuracy comparable to hydrostatic weighing as well determination of bone mineral density.
Timepoint [3] 304552 0
Outcome will be measured at baseline, following 3 month intervention, and after 9 month follow up (12 months after starting study)
Secondary outcome [4] 304553 0
All blood analyses will be performed using standard local procedures, and all children/adolescents will receive an anaesthesia bandage one hour before blood collection. Oxidized-LDL and adiponectin will be measured in plasma using specific ELISA kits (Mercodia, Uppsala, Sweden). Total nitrite (NO2-) concentration will be quantified using a commercially available assay for nitric oxide (NO2-) detection (R&D systems, Inc., Minneapolis, MN, USA). To estimate ß-cell function (%B) and overall insulin sensitivity (%S), the homeostasis assessment model (HOMA) will be used. Gastro intestinal hormones and folate will be measured.
Timepoint [4] 304553 0
Outcome will be measured at baseline, following 3 month intervention, and after 9 month follow up (12 months after starting study)
Secondary outcome [5] 304554 0
Blood pressure will be measured while the participant is sitting and has rested for at least five minutes in a quiet room. It will be measured with a standard automated sphygmomanometer. Blood pressure will be measured at the same time of the day for each individual at pre- and post test. The first reading will be discarded and the mean of the next three consecutive readings with a coefficient of variation below 15% will be used in the study, with additional readings if required.
Timepoint [5] 304554 0
Outcome will be measured at baseline, following 3 month intervention, and after 9 month follow up (12 months after starting study)
Secondary outcome [6] 304555 0
Diet diaries will be given to participants and a four-day record will be requested (three weekdays and one weekend day).
Timepoint [6] 304555 0
This will be gathered prior to the initial assessment, 3-month reassessment and 12-month reassessment.
Secondary outcome [7] 304556 0
An accelerometer will be worn for seven days to measure physical activity.
Timepoint [7] 304556 0
This will be measured for seven days prior to baseline measurement testing, and again for seven days prior to the 3 month and 12 month re-assessments.
Secondary outcome [8] 304557 0
Height, weight and waist circumferences will be measured using standard approaches.
Timepoint [8] 304557 0
Outcome will be measured at baseline, following 3 month intervention, and after 9 month follow up (12 months after starting study)

Eligibility
Key inclusion criteria
Gender: Males and females are eligible. The study will endeavour to recruit approximately equal numbers of males and females.

Body mass index: Obese individuals, with a body mass index greater than or equal to an equivalent of 30kg/m2 in adults are eligible. Eligibility of obese individuals with a BMI greater than 99th percentile (CDC Growth Charts) will be assessed on an individual basis.

Age: Individuals aged 7-16 years old (inclusive) are eligible.

Ethnicity: All ethnic groups are eligible for the study. There is likely to be incidental recruitment of participants of Aboriginal or Torres Strait Islander ethnicity.

Blood pressure: Individuals with blood pressure less than the 95th percentile for systolic or diastolic values measured upon three or more occasions will be eligible

Lipid control: Individuals with fasting total cholesterol less than 5.5mmol/L and low-density lipoprotein cholesterol less than 3.0mmol/L are eligible.

Willingness to participate: Participants must be willing to be randomised to either High Intensity Aerobic Interval Training, Moderate Intensity Exercise or Control groups and to follow the protocol that they have been assigned.

Successful completion of self-monitoring: Successful seven accelerometer compliance and diet diary completion will be an indication of willingness to participate and will be required for eligibility
Minimum age
7 Years
Maximum age
16 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Unwilling to participate or participation in another study
- Coronary heart disease
- Congenital cardiac abnormalities (i.e. anomalous coronary artery origins)
- Family history of hypertrophic obstructive cardiomyopathy
- Any abnormality during the resting or exercise stress echo that indicates it would be unsafe to participate in the intervention
- Self reported kidney failure
- Any major organ transplant
- Considerable pulmonary disease including severe or poorly controlled asthma or exercise induced asthma
- Smoking
- Diabetes
- Epilepsy or history of seizures
- Orthopaedic and/or neurological limitations to exercise
- Diagnosed Attention Deficit Hypersensitivity Disorder (ADHD)
- Medications such as steroids
- Conditions not specifically mentioned above may serve as criteria for exclusion at discretion of the clinical site

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)
Participants will be recruited through advertising at the University of Queensland, as well as GP practices in surrounding suburbs. Alternatively, children who attend an obesity clinic at the Mater Children's Hospital will be approached. If interested, and it appears the participant may be eligible, they will receive a patient information and consent form. The information sheet will outline the aims of the study and also detail procedures involved. If the parent/guardian and child are willing to participant, they will be asked to attend visit 1 where the informed consent form will be signed and selected baseline measures will be taken. After successful completion of the study run-in (diet diary and accelerometer use), participants will be randomly allocated to intervention or control groups.

Allocation in the study will be concealed through central randomisation by computer.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
An increase of 1.5cm/s in peak systolic tissue velocity has been associated with a decrease in mortality in patients with cardiac disease. Using a standard deviation of 1cm/s would allow for an effect size of 1.1. To detect this change with alpha = 0.05 and power = 0.8, we need 27 persons in the study, i.e. 9 persons per group.

An increase of 2.5% in flow-mediated dilation has been associated with reduced cardiac events (cardiac death and hospitalisations) as well as being able to predict adverse outcomes (unstable angina, myocardial infarction and acute heart failure) in patients with suspected coronary artery disease. Using a standard deviation of 2.5% would allow for an effect size of 0.8. To detect this change with alpha = 0.05 and power = 0.8, we need 48 persons in the study, i.e. 16 persons per group.

A 26% decrease in intra-abdominal fat resulting from an exercise program has been correlated with improvements in cardiometabolic parameters. Decreases in triglycerides, total cholesterol to HDL ratio, OGTT-glucose, fasting insulin and leptin are associates with a loss of visceral adipose tissue volume as well as an improvement in cardiorespiratory fitness. Using a standard deviation of 19% would allow for an effect size of 0.9. To detect this change with alpha = 0.05 and power = 0.8, we need 30 persons in the study, i.e. 10 persons per group.

As the measure of flow mediated dilation has the highest number of participants required, this will set the sample size. To allow a loss to follow up of 20%, we will recruit 60 participants. This will allow for power to increase to 0.99 in both the peak systolic tissue velocity measure and the intra-abdominal fat measure.

An intention to treat analysis will be included. An as per protocol analysis will also be included where an adherence of 80% is required to successfully complete the study.

The primary study hypothesis will be tested based on a two-tailed significance level of 0.05.

In reporting the results, we will clearly distinguish between the primary hypothesis and secondary objectives and will discuss results from these different outcome measures appropriately. Significance tests of secondary objectives will also be performed at 0.05 levels of significance.

General linear modelling techniques will be used to determine the effects of the interventions on the outcome measures. Significance will be assumed when P<0.05.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/10/2013
Actual
3/02/2014
Date of last participant enrolment
Anticipated
1/01/2015
Actual
1/10/2015
Date of last data collection
Anticipated
Actual
1/10/2016
Sample size
Target
60
Accrual to date
Final
30
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 1505 0
Mater Children's Hospital - South Brisbane
Recruitment postcode(s) [1] 7344 0
4072 - University Of Queensland
Recruitment postcode(s) [2] 7345 0
4101 - South Brisbane

Funding & Sponsors
Funding source category [1] 287941 0
University
Name [1] 287941 0
Norwegian University of Science and Technology
Country [1] 287941 0
Norway
Primary sponsor type
Individual
Name
Professor Jeff Coombes
Address
Human Movement Studies Building (26B)
The University of Queensland
QLD 4072
Country
Australia
Secondary sponsor category [1] 286661 0
None
Name [1] 286661 0
Address [1] 286661 0
Country [1] 286661 0
Other collaborator category [1] 277611 0
University
Name [1] 277611 0
Norwegian University of Science and Technology
Address [1] 277611 0
Hogskoleringen 1 7491
Trondheim, Norway
Country [1] 277611 0
Norway

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289870 0
Medical Research Ethics Comittee
Ethics committee address [1] 289870 0
Ethics committee country [1] 289870 0
Australia
Date submitted for ethics approval [1] 289870 0
Approval date [1] 289870 0
24/07/2013
Ethics approval number [1] 289870 0
2013000539

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 42850 0
Miss Katrin Dias
Address 42850 0
The School of Human Movement Studies
Blair Drive
The University of Queensland
St Lucia
QLD 4072
Country 42850 0
Australia
Phone 42850 0
+61 7 3365 6983
Fax 42850 0
Email 42850 0
[email protected]
Contact person for public queries
Name 42851 0
Katrin Dias
Address 42851 0
The School of Human Movement Studies
Blair Drive
The University of Queensland
St Lucia
QLD 4072
Country 42851 0
Australia
Phone 42851 0
+61 7 3365 6983
Fax 42851 0
Email 42851 0
[email protected]
Contact person for scientific queries
Name 42852 0
Jeff Coombes
Address 42852 0
The School of Human Movement Studies
Blair Drive
The University of Queensland
St Lucia
QLD 4072
Country 42852 0
Australia
Phone 42852 0
+61 7 3365 6767
Fax 42852 0
Email 42852 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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
No additional documents have been identified.