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Trial registered on ANZCTR


Trial ID
ACTRN12613000771752
Ethics application status
Approved
Date submitted
8/07/2013
Date registered
10/07/2013
Date last updated
2/01/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
Feasibility and efficacy of a 3 month progressive exercise program in patients with non-alcoholic steatohepatitis (NASH) related cirrhosis
Scientific title
A single arm 3 month unblinded intervention of a progressive exercise program examining the impact on hepatic and cardio-metabolic health in subjects with cirrhosis due to nonalcoholic steatohepatitis.
Secondary ID [1] 282679 0
Nil
Universal Trial Number (UTN)
U1111-1138-5745
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
non-alcoholic steatohepatitis (NASH) 289383 0
Liver cirrhosis 289384 0
Condition category
Condition code
Oral and Gastrointestinal 289714 289714 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Metabolic and Endocrine 289897 289897 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study will use a 3 month (12 week) supervised exercise program.
The program will consist of 3 sessions per week (Monday, Wednesday, Friday) and each session will be 60 minutes in duration.
The exercises sessions will include a suitable warm up before moving on to a combination of aerobic and resistance exercises.
Aerobic exercise will be either bicycle or treadmill based and the workload and intensity (% of heart rate maximum) based on the results of pre testing.
Resistance exercises will be primarily machine based, targeting major muscle groups for the upper and lower body. Exercises will include, but may not be limited to, seated leg press, seated leg curl and extension, calf raises, seated chest press, latissimus pull down, bicep curl and tricep extension. Weights used will be based on a percentage of the load lifted at baseline testing and be progressed in small increments each week.
Each exercise session will be supervised by an experienced exercise physiologist accredited with Exercise and Sports Science Australia.
Intervention code [1] 287337 0
Rehabilitation
Comparator / control treatment
N/A - This is a single group study.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 289806 0
Improvement in cardiorespiratory fitness as determined by changes in oxygen uptake (VO2).
Measured by graded cycle ergometry test and cardiopulmonary assessment
Timepoint [1] 289806 0
End of 12 week exercise program
Secondary outcome [1] 303277 0
Improvement in muscular strength as determined by 1 repitition strength tests
Timepoint [1] 303277 0
End of 12 week exercise program
Secondary outcome [2] 303659 0
Serum mediators of inflammation and metabolism (Adiponectin, IL-6, free fatty acids, TNF,C-RP).
Timepoint [2] 303659 0
End of 12 week exercise program
Secondary outcome [3] 303677 0
Serum markers of liver damage (ALT, CK-18)
Timepoint [3] 303677 0
End of 12 week exercise program
Secondary outcome [4] 303678 0
Hepatic steatosis as determined by magnetic resonance spectroscopy
Timepoint [4] 303678 0
End of 12 week exercise program
Secondary outcome [5] 303679 0
Arterial stiffness (measured non-invasively via sphygmocor)
Timepoint [5] 303679 0
End of 12 week exercise program
Secondary outcome [6] 303680 0
Quality of life measures.
Determined via self reported questionaries
Timepoint [6] 303680 0
End of 12 week exercise program

Eligibility
Key inclusion criteria
Liver cirrhosis due to nonalcoholic steatohepatitis
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Inability to provide informed consent
Inability to speak english
Other causes of liver disease as determined by hepatitis B and C serology, auto-antibodies (anti-nuclear, anti-smooth muscle, anti-mitochondrial), alpha-one anti-trypsin level and ceruloplasmin
Hereditary hemochromatosis (C282Y/C282Y or C282Y/H63D HFE gene mutation)
Alcohol consumption greater than 20 grams/day for males, greater than 10 grams/day for females
Secondary causes for NAFLD (corticosteroids, gastro-intestinal bypass
Use of anti-oxidants (vitamin E or C) or anti-TNF agents (pentoxifylline)
Poor glycaemic control (HbA1c greater than 8.5%)
Any musculoskeletal, cardiovascular or neurological conditions that will prevent them form being able to complete a 400m walk or participate in resistance training


Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Vist 0 (Screening) Subjects invited by enrol by treating specialist - Obtain informed consent - Inclusion and Exclusion criteria - Record medical history including alcohol, dietary, and lifestyle - Return within 2 weeks

Visit 1 (Baseline - Week 0) - Inclusion/Exclusion criteria - Physical examination including vital signs, waist and hips measurement - alcohol and lifestyle questionnaires - ECG screen - DEXA scan - MRI scan - SphymoCor scan - Fasting blood test - FibroScan

Visit 1a (Baseline - Week 0) - Physical examination including vital signs, waist and hips measurement - Physical activity and lifestyle questionnaires - Cardiopulmonary test (stationary cycle) - Strength tests (1 RM) - Physical function tests (400m / 6 minute walk, timed stair climb, 3m walk (timed up and go)

Visit 2 (Week 4) - Physical examination including vital signs, waist and hips measurement - Fasting blood test

Visit 3 (Week 8) - Physical examination including vital signs, waist and hips measurement - Fasting blood test

Visit 4 (End of study - Week 12) - Physical examination including vital signs, waist and hips measurement - alcohol and lifestyle questionnaires - DEXA scan - MRI scan - SphymoCor scan - Fasting blood test - FibroScan

Visit 4a (End of Study - Week 12) - Physical examination including vital signs, waist and hips measurement - Physical activity and lifestyle questionnaires - Cardiopulmonary test (stationary cycle) - Strength tests (1 RM) - Physical function tests (400m / 6 minute walk, timed stair climb, 3m walk (timed up and go)

Exercise sessions will commence the first Monday following the baseline testing and will comprise of three 1 hour sessions per week. Following a warm up a combination of aerobic and resistance exercises will be prescribed. BP,HR, fatigue and general health will be recorded at each session.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
NA
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Paired analysis using Wilcoxon rank sum test or paired t test for primary and seconary outcomes.

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)
WA
Recruitment hospital [1] 1128 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 6971 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 287452 0
University
Name [1] 287452 0
School of Medicine and Pharmacology, University of Western Australia
Address [1] 287452 0
SMP, UWA
G Block, 4th Floor
Sir Charles Gairdner Hospital
Hospital Avenue
Nedlands WA 6009
Country [1] 287452 0
Australia
Primary sponsor type
University
Name
School of medicine and pharmacology, University of Western Australia
Address
SMP, UWA
G Block, 4th Floor
Sir Charles Gairdner Hospital
Hospital Avenue
Nedlands WA 6009
Country
Australia
Secondary sponsor category [1] 286196 0
None
Name [1] 286196 0
Address [1] 286196 0
Country [1] 286196 0
Other collaborator category [1] 277452 0
University
Name [1] 277452 0
Edith Cowan University
Address [1] 277452 0
270 Joondalup Drive
Joondalup WA 6027
Country [1] 277452 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289428 0
Human Research Ethics Committee, Sir Charles Gairdner Hospital
Ethics committee address [1] 289428 0
E Block, 1st floor Sir Charles Gairdner Hospital
Hospital Avenue Nedlands, WA, 6009
Ethics committee country [1] 289428 0
Australia
Date submitted for ethics approval [1] 289428 0
Approval date [1] 289428 0
16/05/2013
Ethics approval number [1] 289428 0
2013-011

Summary
Brief summary
STUDY DESIGN:
This study will use a single group design to examine the effects of an exercise intervention on patient outcomes with pre and post assessment.
The aim of the study is to improve the hepatic and cardio-metabolic profile of these patients.

OUTCOME MEASURES:
After referral and screening by the treating specialist participants will undergo baseline assessment. Outcomes will include:

- Hepatic steatosis
- Plasma lipid profile, insulin, glucose, HOMA2, markers of liver damage (ALT, CK18) and liver enzymes
- Arterial stiffness (measured non-invasively via PWA/PWV)
- Body composition (DEXA / MRI)
- Cardiorespiratory fitness
- Muscular strength and physical function

EXERCISE INTERVENTION:
Participants will undertake supervised training 3 days per week consisting of a combination of aerobic and resistance training. training load and volumes will be individualized based on pre assessment results and progressed throughout the study.

SIGNIFICANCE:
This study will establish the feasibility and efficacy of an exercise intervention on this patient population and will help inform the design of future larger multi-centre studies of exercise as an adjuvant therapy in advanced liver disease.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 40790 0
A/Prof Leon Adams
Address 40790 0
Liver Transplant Unit
G Block, 6th Floor
Sir Charles Gairdner Hospital
Hospital Avenue
Nedlands, WA, 6009
Country 40790 0
Australia
Phone 40790 0
+61 8 93463228
Fax 40790 0
+61 8 93463098
Email 40790 0
leon.adams@uwa.edu.au
Contact person for public queries
Name 40791 0
Miss Helena Ching
Address 40791 0
Liver Transplant Unit
G Block, 6th Floor
Sir Charles Gairdner Hospital
Hospital Avenue
Nedlands, WA, 6009
Country 40791 0
Australia
Phone 40791 0
+61 8 93463228
Fax 40791 0
+61 8 93463098
Email 40791 0
helena.ching@health.wa.gov.au
Contact person for scientific queries
Name 40792 0
A/Prof Leon Adams
Address 40792 0
Liver Transplant Unit
G Block, 6th Floor
Sir Charles Gairdner Hospital
Hospital Avenue
Nedlands, WA, 6009
Country 40792 0
Australia
Phone 40792 0
+61 8 93463228
Fax 40792 0
+61 8 93463098
Email 40792 0
leon.adams@uwa.edu.au