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Trial registered on ANZCTR


Registration number
ACTRN12616000305426
Ethics application status
Approved
Date submitted
1/03/2016
Date registered
9/03/2016
Date last updated
3/03/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
High intensity exercise for non-alcoholic steatohepatitis- is it safe, effective, and feasible in practice?
Scientific title
In patients with non-alcoholic steatohepatitis, is high intensity interval training safe, feasible and effective for improving fitness and insulin sensitivity.
Secondary ID [1] 288666 0
nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
non-alcoholic steatohepatitis 297856 0
Condition category
Condition code
Metabolic and Endocrine 298031 298031 0 0
Metabolic disorders
Oral and Gastrointestinal 298065 298065 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
Participants will receive 12 weeks of supervised High Intensity Interval Training (HIIT), followed by 12 weeks of home-based HIIT (in an unsupervised environment). The HIIT protocol will consist of: warm-up for 5 min and at 60% of maximal heart rate (HRmax) followed by 4 x 4 min intervals at 85-95% HRmax interspersed with 3 min ‘recovery’ periods at 60% HRmax, then a 5 min cool down. All training will be conducted on three days per week. Weeks 1-12 will be supervised by an Accredited Exercise Physiologist and weeks 13-24 will be home-based (unsupervised).. Sessions will be generally conducted one-on-one with a maximum of 3 participants training at one time. All supervised sessions will be recorded on a clinical resource form and all home-based sessions will be recorded in an exercise log. Participants will be given a Polar heart rate monitor and taught how to monitor the intensity of their exercise sessions using heart rates and ratings of perceived exertion (RPE). All supervised exercise will be conducted on a treadmill, unless orthopaedic limitation exists in which a cycle ergometer will be used. Home-based exercise will involve walking/jogging or cycling depending on the access to exercise equipment and preferences of the individual participant.
Intervention code [1] 294080 0
Lifestyle
Intervention code [2] 294115 0
Treatment: Other
Comparator / control treatment
Participants randomised to the control group will perform 12 weeks of stretching on three days per week and then be invited to complete the HIIT protocol. Stretches will be performed for all major muscle groups (e.g. calves, quadriceps, hamstrings, pectorals, neck, arms) and held for 30-60 seconds and repeated three times. Stretch sessions will run for 30-45 minutes. Sessions will be generally conducted one-on-one with a maximum of 3 participants training at one time. All supervised sessions will be recorded on a clinical resource form.

The HIIT protocol will be commenced after week 12 assessments and will be identical to the supervised HIIT protocol (12 weeks, i.e. weeks 13-24). The 12-week home based phase will be identical to that described for the intervention group (i.e. weeks 25-36)

On completion of the HIIT intervention, all participants (n=22) will be prescribed an on-going exercise program based on an equivalent type and intensity of exercise, modified for an unsupervised home/gym environment.
Control group
Placebo

Outcomes
Primary outcome [1] 297544 0
Change in insulin sensitivity:assessed via the euglycemic hyperinsulinaemic clamp
Timepoint [1] 297544 0
This will be assessed at baseline and week 12 for the HIIT intervention, and baseline, week 12 and week 24 for the stretch control group who then go on to do HIIT.
Primary outcome [2] 297545 0
Change in cardiorespiratory fitness (VO2peak, assessed via expired air gas analysis during an exercise stress test)
Timepoint [2] 297545 0
This will be assessed at baseline and week 12 for the HIIT intervention, and baseline, week 12 and week 24 for the stretch control group who then go on to do HIIT.
Secondary outcome [1] 321360 0
Safety (adverse events). All participants will be asked to report physical symptoms, musculoskeletal injuries, acute illnesses, and health care utilisation. These will be recorded on session training sheets during the supervised phase and unsupervised phase. Any concerns about continued participant involvement will be raised with the participant’s GP or the study physician.
Timepoint [1] 321360 0
This will be assessed at baseline and week 12 for the HIIT intervention, and baseline, week 12 and week 24 for the stretch control group who then go on to do HIIT.
Secondary outcome [2] 321361 0
Change in body composition ( total body fat and lean muscle mass via dual energy X-ray absorbtiometry (DXA) )
Timepoint [2] 321361 0
This will be assessed at baseline and week 12 for the HIIT intervention, and baseline, week 12 and week 24 for the stretch control group who then go on to do HIIT.
Secondary outcome [3] 321362 0
Change in resting blood pressure (manual cuff)
Timepoint [3] 321362 0
This will be assessed at baseline and week 12 for the HIIT intervention, and baseline, week 12 and week 24 for the stretch control group who then go on to do HIIT.
Secondary outcome [4] 321363 0
Change in oxidative stress and antioxidant markers (composite outcomes) (high-mobility group protein B1 (HMGB-1), total F2-isoprostanes, protein carbonyls and glutathione peroxidase activity) via serum assays.
Timepoint [4] 321363 0
This will be assessed at baseline and week 12 for the HIIT intervention, and baseline, week 12 and week 24 for the stretch control group who then go on to do HIIT.
Secondary outcome [5] 321364 0
Psychosocial constructs, barriers and enablers of exercise (composite outcome) via questionnaires designed for this study and via semi-structured interview.
Timepoint [5] 321364 0
This will be assessed at baseline and week 12 and post-12 weeks of home based intervention (i.e.wk 24) for the HIIT intervention, and baseline, week 12 and week 24 and post 12 weeks home-based intervention (i.e. wk 36) for the stretch control group who then go on to do HIIT.
Secondary outcome [6] 321492 0
adherence via attendance records (supervised phase) and by daily exercise log and a 7 day accelerometer (during home-based period).
Timepoint [6] 321492 0
This will be assessed at week 12 and post-12 weeks of home based intervention (i.e.wk 24) for the HIIT intervention, and baseline, week 12 and week 24 and post 12 weeks home-based intervention (i.e. wk 36) for the stretch control group who then go on to do HIIT.
Secondary outcome [7] 321493 0
Visceral and liver fat via Magnetic resonance imaging and spectroscopy
Timepoint [7] 321493 0
This will be assessed at baseline and week 12 for the HIIT intervention, and baseline, week 12 and week 24 for the stretch control group who then go on to do HIIT.
Secondary outcome [8] 321494 0
Liver stiffness via transient elastography
Timepoint [8] 321494 0
This will be assessed at baseline and week 12 for the HIIT intervention, and baseline, week 12 and week 24 for the stretch control group who then go on to do HIIT.
Secondary outcome [9] 321498 0
Change in inflammatory markers (total and High Molecular Weight adiponectin, high sensitivity C-reactive protein (hs-CRP), IL-6, IL-10, tumour necrosis factor alpha (TNF-a)) assessed via blood test.
Timepoint [9] 321498 0
This will be assessed at baseline and week 12 for the HIIT intervention, and baseline, week 12 and week 24 for the stretch control group who then go on to do HIIT.
Secondary outcome [10] 321499 0
CK-18, via serum assay
Timepoint [10] 321499 0
This will be assessed at baseline and week 12 for the HIIT intervention, and baseline, week 12 and week 24 for the stretch control group who then go on to do HIIT.
Secondary outcome [11] 321500 0
Vascular structure and function using a) carotid artery intima media thickness using Doppler ultrasound, b) brachial artery reactivity using Doppler ultrasound and c) pulse wave velocity using a SpygmoCor.
Timepoint [11] 321500 0
This will be assessed at baseline and week 12 for the HIIT intervention, and baseline, week 12 and week 24 for the stretch control group who then go on to do HIIT.
Secondary outcome [12] 321501 0
Heart Rate Variability, via ECG
Timepoint [12] 321501 0
This will be assessed at baseline and week 12 for the HIIT intervention, and baseline, week 12 and week 24 for the stretch control group who then go on to do HIIT.
Secondary outcome [13] 321502 0
Blood lipids: the lipid profile from plasma will include assessment of total cholesterol (TC), very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides (TG) using cholesterol lipid assay kit
Timepoint [13] 321502 0
This will be assessed at baseline and week 12 for the HIIT intervention, and baseline, week 12 and week 24 for the stretch control group who then go on to do HIIT.
Secondary outcome [14] 332373 0
Health related quality of life via the Chronic Liver Disease Questionnaire. This questionnaire was added after 1 participant had been enrolled.
Timepoint [14] 332373 0
This will be assessed at baseline and week 12 for the HIIT intervention, and baseline, week 12 and week 24 for the stretch control group who then go on to do HIIT.

Eligibility
Key inclusion criteria
Men and women who are not currently meeting physical activity guidelines (<150 minutes of moderate or <75 min of vigorous exercise per week), aged 18-70 years, with biopsy-proven NASH.
Minimum age
18 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Unstable angina; Recent (4 weeks) myocardial infarction; Coronary Artery Disease; Uncompensated heart failure; New York Heart Association (NYHA) Functional Classification II-IV; Severe valvular illness; Pulmonary disease; Uncontrolled hypertension (systolic blood pressure > 200 mmHg and/or diastolic blood pressure >110 mmHg); Renal failure (Chronic Kidney Disease stages III-V); Orthopedic/neurological limitations; Cardiomyopathy; Planned operations during the research period; Physical impairment limiting the ability to exercise; Drug or alcohol abuse; Planning to or participation in another study; Not willing to sign the consent from; Females pregnant or expecting to be pregnant during the study period; Lactating females; Contraindication to exercise testing/training; Medication affecting insulin sensitivity and/or evidence of cirrhosis; Any other reason which would limit their ability to participate in this study.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



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

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)
QLD

Funding & Sponsors
Funding source category [1] 293022 0
Other
Name [1] 293022 0
Exercise and Sports Science Australia
Address [1] 293022 0
Locked Bag 102, Albion DC, QLD 4010
Country [1] 293022 0
Australia
Funding source category [2] 295822 0
Charities/Societies/Foundations
Name [2] 295822 0
Diabetes Australia Research Program
Address [2] 295822 0
GPO Box 3156 Canberra,
ACT, 2601,
Australia
Country [2] 295822 0
Australia
Primary sponsor type
University
Name
The University of Queensland
Address
School of Human Movement and Nutrition Sciences
The University of Queensland
St Lucia, 4072
Queensland, AUSTRALIA
Country
Australia
Secondary sponsor category [1] 291798 0
Hospital
Name [1] 291798 0
Princess Alexandra Hospital
Address [1] 291798 0
199 Ipswich Rd, Woolloongabba QLD 4102
Country [1] 291798 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294532 0
Metro South Human Research Ethics Committee
Ethics committee address [1] 294532 0
PAH Centres for Health Research
Level 7, Translational Research Institute
37 Kent Street
Woolloongabba QLD 4102
Ethics committee country [1] 294532 0
Australia
Date submitted for ethics approval [1] 294532 0
Approval date [1] 294532 0
05/01/2016
Ethics approval number [1] 294532 0
HREC/15/QPAH/747
Ethics committee name [2] 294533 0
The University of Queensland HREC
Ethics committee address [2] 294533 0
Ethics committee country [2] 294533 0
Date submitted for ethics approval [2] 294533 0
Approval date [2] 294533 0
10/01/2016
Ethics approval number [2] 294533 0
2016000010

Summary
Brief summary
Regular aerobic exercise has now been established as an effective therapy for reducing liver fat in patients with non-alcoholic fatty liver disease (NAFLD), even in the absence of weight loss. However the efficacy of regular exercise in progressive liver disease such as non-alcoholic steatohepatitis (NASH) is yet to be established. Recent evidence has suggested that high intensity exercise may be required for benefit and, as such, high intensity interval training (HIIT) may be an effective modality for improving cardiovascular, metabolic and liver health in patients with NASH. A key feature to the success of any exercise intervention is the ability to adhere to the intervention in the long-term. The ability to perform HIIT on a regular basis, in an unsupervised environment has yet to be determined.
The aims are to i) examine the efficacy of a 12 week supervised exercise intervention involving high-intensity interval training (HIIT) in patients with biopsy-proven non-alcoholic steatohepatitis (NASH) for improving cardiorespiratory fitness (CRF), and ii) examine the safety and feasibility of regular HIIT in patients with NASH both when performed under supervision and when performed unsupervised (home-based, for 12 weeks). We hypothesise that, compared with control: i) the HIIT intervention will significantly improve CRF, and ii) the HIIT intervention will be safe and feasible for sustaining both supervised and unsupervised exercise adherence in people with NASH.
Eligible participants (n=22) will be randomised into 12 weeks of HIIT (n=11) or a control (n=11). The primary analysis will examine the efficacy of 12 weeks of HIIT on changes in cardiorespiratory fitness, body composition, liver fat, liver stiffness, abdominal visceral fat, vascular function, and other cardio-metabolic risk factors, compared with control. The supervised HIIT training will begin with a warm-up for 5 min and at 60% of maximal heart rate (HRmax) followed by 4 x 4 min intervals at 85-95% HRmax interspersed with 3 min ‘recovery’ periods at 60% HRmax, then a 5 min cool down. Participants randomised to the control group will perform 12 weeks of stretching and then be invited to complete the HIIT protocol. On completion of the HIIT intervention, all participants (n=22) will be prescribed an on-going exercise program based on an equivalent type and intensity of exercise, modified for an unsupervised home/gym environment. Feasibility and adherence will be assessed via self-administered questionnaires and focus group after 12 weeks of home based exercise.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 64042 0
Dr Shelley Keating
Address 64042 0
Centre for Research on Exercise, Physical Activity and Heath (CRExPAH)
School of Human Movement and Nutrition Sciences
The University of Queensland
HMS Building (26B)
St Lucia, 4072
Queensland, AUSTRALIA
Country 64042 0
Australia
Phone 64042 0
+61733469999
Fax 64042 0
Email 64042 0
s.keating@uq.edu.au
Contact person for public queries
Name 64043 0
Dr Shelley Keating
Address 64043 0
Centre for Research on Exercise, Physical Activity and Heath (CRExPAH)
School of Human Movement and Nutrition Sciences
The University of Queensland
HMS Building (26B)
St Lucia, 4072
Queensland, AUSTRALIA
Country 64043 0
Australia
Phone 64043 0
+61733469999
Fax 64043 0
Email 64043 0
s.keating@uq.edu.au
Contact person for scientific queries
Name 64044 0
Dr Shelley Keating
Address 64044 0
Centre for Research on Exercise, Physical Activity and Heath (CRExPAH)
School of Human Movement and Nutrition Sciences
The University of Queensland
HMS Building (26B)
St Lucia, 4072
Queensland, AUSTRALIA
Country 64044 0
Australia
Phone 64044 0
+61733469999
Fax 64044 0
Email 64044 0
s.keating@uq.edu.au

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