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Trial registered on ANZCTR


Registration number
ACTRN12614000723684
Ethics application status
Approved
Date submitted
23/06/2014
Date registered
8/07/2014
Date last updated
8/07/2014
Type of registration
Retrospectively registered

Titles & IDs
Public title
Exercise and liver fat reduction in pre-diabetes: moving beyond weight loss
Scientific title
In overweight/obese adults, which modality and dose of exercise training compared to placebo control reduces liver fat?
Secondary ID [1] 284855 0
Nil
Universal Trial Number (UTN)
Nil
Trial acronym
Nil
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-alcoholic fatty liver disease 292249 0
Obesity 292309 0
Condition category
Condition code
Metabolic and Endocrine 292590 292590 0 0
Metabolic disorders
Oral and Gastrointestinal 292645 292645 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Our proposed research will use innovative and valid, non-invasive techniques, including proton magnetic resonance spectroscopy (MRS), to measure the effect of 8 weeks of: i) low-intensity/low energy expenditure aerobic exercise training (LO-LO); ii) low-intensity/high energy expenditure aerobic exercise (LO-HI) iii) high-intensity/low energy expenditure aerobic exercise training (HI-LO) iv) progressive resistance (PRT) and v) placebo control on liver fat content, abdominal triglyceride partitioning (subcutaneous and visceral fat), serum aminotransferases, blood lipids/hormones, insulin sensitivity and aerobic fitness (VO2max/peak) in overweight and obese individuals with pre-diabetes.

Specifically, subjects allocated to LO-LO will receive a supervised progressive cycling exercise program involving 2 days of exercise per week with one additional session at home each week, 45 minutes per session at 50% of maximal aerobic power (VO2max) (135 min per week). Subjects allocated to LO-HI will undertake 3 days of supervised exercise per week with one additional session at home each week, 60 minutes per session at 50% of VO2max (240 min per week); those in HI-LO will receive 2 days of supervised exercise per week with one additional session at home each week, 45 minutes per session at 70% of VO2max (135 min per week). Subjects allocated to PRT will receive a supervised progressive resistance training program involving 3 days of exercise per week, 8-10 exercises per session, 1-3 sets per exercise at 60-80% of 1-repetition maximum (1-RM) with sessions lasting 45- 60 minutes including warm up and cool down on a cycle ergometer.

For the LO-LO, the LO-HI and HI-LO groups all supervised exercise sessions will be performed on a stationary cycle ergometer and supervised on a one-on-one basis by an exercise physiologist. The additional home-based session will involve brisk walking at the prescribed intensity. The PRT sessions will also be supervised by an exercise physiologist on a one-on-one basis.

All exercise interventions will be progressed. The LO-LO group will begin cycling for 30 minutes at 50% V02 peak and this will progress to 45 minutes by week 3 of the intervention. The HI-LO group will begin cycling at 50% intensity for 30 minutes and this will progress to 45 minutes at 70% V02 peak by week 3 of the intervention. The LO-HI group will begin cycling for 45 minutes at 50% intensity and this will progress to 60 minutes by week 3 of the intervention. Heart rates and ratings of perceived exertion will be continuously monitored and the power output (Watts) increased in accordance with training adaptations over the 8 weeks to keep the same relative exercise intensity.


Supervised sessions will be logged by the exercise physiology with heart rates, ratings of perceived exertion and blood pressure recorded. Adherence to home based sessions will be monitored using a home log book and record heart rates and ratings of perceived exertion.
Intervention code [1] 289652 0
Lifestyle
Intervention code [2] 289682 0
Treatment: Other
Comparator / control treatment
Subjects allocated to the placebo control group will undertake three days of stretching, core strength and fit-ball exercise for 15-30 minutes per session. These subject will receive exercise instruction (home-based) with fortnightly supervised training sessions. The supervised sessions will occur at the training institute and will involve instruction of a new set of stretches/fit ball exercises to be performed at home for the following 2 weeks. The home-based sessions will be logged in a home diary in order to monitor compliance. The control group is designed to elicit no cardiometabolic benefit and to control for factors of attention and participation in a lifestyle program.
Control group
Placebo

Outcomes
Primary outcome [1] 292446 0
Intrahepatic lipid concentration as assessed using proton magnetic resonance spectroscopy (MRS)
Timepoint [1] 292446 0
Baseline and and post- 8 week intervention
Secondary outcome [1] 308970 0
Abdominal fat content (including subcutaneous and visceral adipose tissue) as assessed magnetic resonance imaging (MRI)
Timepoint [1] 308970 0
Baseline and post- 8 week intervention
Secondary outcome [2] 308971 0
Cardiorespiratory fitness assessed via graded exercise test to maximal aerobic capacity. The test will start at 35 Watts and 65 Watts for men and women respecitively and increase by 25W every 2.5 minutes until volitional fatigue or other test termination criteria reached.
Timepoint [2] 308971 0
Baseline and post- 8 week intervention
Secondary outcome [3] 308972 0
serum aminotransferases assessed via fasting blood test
Timepoint [3] 308972 0
Baseline and post-8 week intervention
Secondary outcome [4] 308973 0
Blood lipids/ hormones assessed via fasting blood test
Timepoint [4] 308973 0
Baseline and post- 8 week intervention
Secondary outcome [5] 308974 0
insulin sensitivity assessed via oral glucose tolerance test
Timepoint [5] 308974 0
Baseline and post- 8 week intervention

Eligibility
Key inclusion criteria
Subjects must be inactive (exercising less than 3 days per week), overweight or obese adults (Body Mass Index > 25 kg/ meters squared), diagnosed with pre-diabetes in the last two years (defined as impaired fasting glucose and/or impaired glucose tolerance) and 29- 59 yrs of age
Minimum age
29 Years
Maximum age
59 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Subjects will be excluded if taking lipid lowering or insulin sensitizing medication or if they report a high alcohol intake (> 20 g/day of ethanol)

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)
Randomization will take place after baseline assessments by equally distributed pre-generated lists (www.randomization.com) of permuted blocks. Allocation will be concealed by use of sealed opaque envelopes in which the trial participiant opens to reveal group allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Type of endpoint(s)
Statistical methods / analysis


125 participants will undertake this study (n= 25 per group).
Sample size estimate was based on a projected change in IHTG (intrahepatic triglyceride) in the aerobic exercise group of 10% versus 0% in the control group, for a total effect size = 0.81, based on papers with an intervention similar to our design that were included in our meta-analysis of previous studies. A priori, two-tailed power calculations at an alpha of 0.05 and beta of 0.20 gave an actual power of 0.801 for a sample size of 25 in each group using G-Power software (University of Trier, Trier, Germany).


Data will be analysed using the Statistical Package for Social Science (SPSS). A two-way ANOVA for repeated measures will be used to compare time and treatment effects. Significance will be set at p<0.05. Intention to treat analysis will be employed with imputed means for missing data.

Specifically, the effect of exercise volume/energy expenditure will be assessed by comparison of LO-LO and LO-HI; the effect of exercise intensity will the assessed by comparison of LO-LO and HI-LO; and the effect of exercise modality will be compared by comparison of PRT with LO-LO and HI-LO and Placebo Control by 2-way repeated measures ANOVA

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)
NSW

Funding & Sponsors
Funding source category [1] 289465 0
Charities/Societies/Foundations
Name [1] 289465 0
Diabetes Australia Research Trust
Address [1] 289465 0
Diabetes Australia
GPO BOX 3156
CANBERRA ACT 2601
Country [1] 289465 0
Australia
Primary sponsor type
Individual
Name
Dr Nathan Johnson
Address
The University of Sydney
Discipline of Exercise and Sport Science
PO Box 170,
Lidcombe
NSW, 2141
C42
Country
Australia
Secondary sponsor category [1] 288149 0
Individual
Name [1] 288149 0
Dr Kieron Rooney
Address [1] 288149 0
The University of Sydney
Discipline of Exercise and Sport Science
PO Box 170,
Lidcombe,
NSW, 2141
C42
Country [1] 288149 0
Australia
Secondary sponsor category [2] 288150 0
Individual
Name [2] 288150 0
Professor Ian Caterson
Address [2] 288150 0
Boden Institute of Obesity, Nutrition, Exercise and Eating Disorders, Univerity of Sydney.
Medical Foundation Building (K25)
92-94 Parramatta Road,
Camperdown
NSW 2050
Country [2] 288150 0
Australia
Secondary sponsor category [3] 288151 0
Individual
Name [3] 288151 0
Professor Jacob George
Address [3] 288151 0
Department of Medicine,
Westmead Hospital,
PO Box 412
Westmead,
NSW 2145
Country [3] 288151 0
Australia
Secondary sponsor category [4] 288152 0
Individual
Name [4] 288152 0
Ms Shelley Keating
Address [4] 288152 0
The University of Sydney
Discipline of exercise and Sport Science
PO Box 170,
Lidcombe,
NSW, 2141
C42
Country [4] 288152 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291224 0
Human Research Ethics Committees (HRECs) of the University of Sydney
Ethics committee address [1] 291224 0
Human Ethics Office
Margaret Telfer Building (K07)
University of Sydney
NSW 2006
Ethics committee country [1] 291224 0
Australia
Date submitted for ethics approval [1] 291224 0
Approval date [1] 291224 0
01/04/2011
Ethics approval number [1] 291224 0
03-2011/13364

Summary
Brief summary
Exercise per se has recently been shown to be effective in the management of fatty liver, independent of weight loss. Sustained weight loss is becoming increasingly recognised as an unrealistic and unsustainable outcome of lifestyle intervention. There are currently no practical guidelines for physical activity in fatty liver disease. This research aims to examine the components of regular exercise which result in an hepatic benefit by comparing i) low-intensity/low energy expenditure aerobic exercise training (LO-LO); ii) low-intensity/high energy expenditure aerobic exercise (LO-HI) iii) high-intensity/low energy expenditure aerobic exercise training (HI-LO) iv) progressive resistance (PRT) and v) a placebo control on hepatic and visceral fat, liver enzymes, and other health outcomes in overweight and obese sedentary individuals with pre-diabetes.

We hypothesize that: the high-intensity/low energy expenditure aerobic exercise training will result in greater improvement in liver fat content than a) low-intensity/low energy expenditure aerobic exercise training b) low-intensity/high energy expenditure aerobic exercise training and c) placebo control; that the progressive resistance training will result in greater improvement in liver fat content than a) low-intensity/low energy expenditure aerobic exercise training b) low-intensity/high energy expenditure aerobic exercise training and c) placebo control; and that all exercise training groups will result in greater improvement in liver fat content than the placebo control group
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 49402 0
Dr Nathan Johnson
Address 49402 0
The Univerity of Sydney
Discipline of Exercise and Sport Science
PO Box 170,
Lidcombe
NSW, 2141
C42
Country 49402 0
Australia
Phone 49402 0
+612 9351 9137
Fax 49402 0
Email 49402 0
nathan.johnson@sydney.edu.au
Contact person for public queries
Name 49403 0
Ms Shelley Keating
Address 49403 0
The Univerity of Sydney
Discipline of Exercise and Sport Science
PO Box 170,
Lidcombe
NSW, 2141
C42
Country 49403 0
Australia
Phone 49403 0
+61405735200
Fax 49403 0
Email 49403 0
shelley.keating@sydney.edu.au
Contact person for scientific queries
Name 49404 0
Dr Nathan Johnson
Address 49404 0
The Univerity of Sydney
Discipline of Exercise and Sport Science
PO Box 170,
Lidcombe
NSW, 2141
C42
Country 49404 0
Australia
Phone 49404 0
+612 9351 9137
Fax 49404 0
Email 49404 0
nathan.johnson@sydney.edu.au

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