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Trial registered on ANZCTR


Registration number
ACTRN12616000992404
Ethics application status
Approved
Date submitted
18/07/2016
Date registered
28/07/2016
Date last updated
28/07/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
Effects of a lifestyle intervention in patients with Non-Alcoholic Fatty Liver Disease or Hepatitis C
Scientific title
Effects of a lifestyle intervention in patients with Non-Alcoholic Fatty Liver Disease or Hepatitis C
Secondary ID [1] 289670 0
Grant 219282 – Centre of Clinical Research Excellence to Improve Outcomes in Chronic Liver
Disease (NHMRC)
Secondary ID [2] 289676 0
Nil
Universal Trial Number (UTN)
U1111-1184-9549
Trial acronym
n/a
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Alcoholic Fatty Liver Disease (NAFLD) 299471 0
Hepatitis C 299539 0
Elevated liver enzymes 299540 0
Overweight/Obesity 299541 0
Metabolic Syndrome 299542 0
Impaired glucose tolerance 299544 0
Dyslipidemia 299545 0
Condition category
Condition code
Metabolic and Endocrine 299449 299449 0 0
Metabolic disorders
Oral and Gastrointestinal 299450 299450 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Infection 299451 299451 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The lifestyle intervention was conducted at Westmead Hospital, Australia from 2004 to 2007 in patients diagnosed with non-alcoholic fatty liver disease. Subjects were randomised at baseline to one of 3 intervention arms (Group A, B or C) or a control group.
Group A was a low-intensity intervention consisting of 3 consultations over four weeks (Baseline, 2 and 4 weeks).
Group B was a moderate-intensity 10 week consisting of 6 fortnightly consultations (baseline, Weeks 2, 4, 6, 8 and 10).
Group C had an identical intervention as Group B in the first 3 months and then received a telephone-based maintenance program through to 12 months to assess whether such a program would result in an improved level of sustained change. Telephone calls were made to participants in Group C at 4, 5, 6, 8 and 10 months from baseline.

The intervention developed for this study was based on behavioural theory and consisted of strategies aimed at affecting mediators and addressing specific determinants of behaviours was based on elements derived from Social Cognitive Theory, the Transtheoretical Model, the Theory of Self-Determination and Motivational Interviewing. The intervention consisted of individual face to face counselling sessions delivered by dietitians/exercise physiologists. The initial session was 1 hour and the review sessions were 45 -60 minutes. The counselling aimed to assist participants in making positive changes to physical activity and dietary behaviours.
Participants were encouraged to increase both planned and incidental moderate-intensity physical activity to achieve at least 150 minutes per week for general health and 200 minutes or more per week for weight loss. They were encouraged to aim for a diet low in saturated fats and processed food and a reduction in daily energy intake for weight loss.
The counselling sessions included discussion of the participant’s and the Intervention Goals, reflection on current diet and physical activity habits, Goal Setting, review of participants, self-efficacy and motivation for change, discussion of barriers to change, information and education to support dietary and physical activity changes along with review and discussion of progress. Databases were developed to collect data on participant attendance and record implementation of telephone consultations.
Intervention code [1] 295297 0
Lifestyle
Intervention code [2] 295298 0
Behaviour
Intervention code [3] 295299 0
Treatment: Other
Comparator / control treatment
Participants in the control group received an initial consultation at baseline in which their biochemical, anthropometric, physical activity and dietary assessment results were provided along with an interpretation of the results. This included a written report containing the participant’s results and the reference or ‘ideal’ range for each result. The nutrition and physical activity intervention goals of the intervention were explained to the controls at this consultation. However, they were not provided with support, advice or assistance in making changes and were similarly not advised to not make changes if they wanted to do so.
This 1 hour face-to-face individual consultation was provided by an exercise physiologist/dietitian. The control phase was limited to 3 months as it was not considered ethical to withhold the intervention from patients for a longer period of time. At the end of the 3 month control phase, participants initially randomized as controls were invited to participate in the intervention phase. Those who accepted this offer underwent randomisation to one of the three intervention groups.
Control group
Active

Outcomes
Primary outcome [1] 298943 0
Alanine aminotransferase (ALT) U/L (serum assay)
Performed using a conventional automated analyser in the Department of Pathology, Westmead Hospital.
Timepoint [1] 298943 0
Baseline and 3, 6, 12, 18 and 24 months post commencement of the intervention.
Primary outcome [2] 298945 0
Weight (kg) (electronic SECA scales (Model number 707 1314004).
Timepoint [2] 298945 0
Baseline and 3, 6, 12, 18 and 24 months post commencement of the intervention.
Primary outcome [3] 298946 0
Physical Activity (minutes per week)
The Active Australia Survey, an established and reliable self-report measure was used to assess physical activity.
Timepoint [3] 298946 0
Baseline and 3, 6, 12, 18 and 24 months post commencement of the intervention.
Secondary outcome [1] 325718 0
Gamma glutamyl transpeptidase (GGT) (serum assay)
Performed using a conventional automated analyser in the Department of Pathology, Westmead Hospital.
Timepoint [1] 325718 0
Baseline and 3, 6, 12, 18 and 24 months post commencement of the intervention.
Secondary outcome [2] 325719 0
Aspartate aminotransferase (ASP) (serum assay)
Performed using a conventional automated analyser in the Department of Pathology, Westmead Hospital.
Timepoint [2] 325719 0
Baseline and 3, 6, 12, 18 and 24 months post commencement of the intervention.
Secondary outcome [3] 325720 0
Waist circumference (cm)
This was undertaken following protocols from the International Society for the Advancement of Kinanthropometry (ISAK). Waist measurement was taken at two points: i) the mid-point between the lower costal border and the iliac crest and ii) the umbilicus. For each of these points, 3 measures were taken using a steel tape measure and the average calculated to provide the waist measurement at each assessment timepoint.
Timepoint [3] 325720 0
Baseline and 3, 6, 12, 18 and 24 months post commencement of the intervention.
Secondary outcome [4] 325721 0
Systolic Blood Pressure (mmHg)
lood Pressure was assessed with a digital sphygmomanometer. Blood Pressure was taken on the right arm with the patient seated and long-sleeved clothing removed from the arm. The measurement procedure was undertaken three times, with the staff loosening the cuff between each measurement and waiting 3 to 5 min between each measurement. The three results were recorded with the average value used as the result.
Timepoint [4] 325721 0
Baseline and 3, 6, 12, 18 and 24 months post commencement of the intervention.
Secondary outcome [5] 325722 0
Diastolic Blood Pressure (mmHg)
Blood Pressure was assessed with a digital sphygmomanometer. BP was taken on the right arm with the patient seated and long-sleeved clothing removed from the arm. The measurement procedure was undertaken three times, with the staff loosening the cuff between each measurement and waiting 3 to 5 min between each measurement. The three results were recorded with the average value used as the result.
Timepoint [5] 325722 0
Baseline and 3, 6, 12, 18 and 24 months post commencement of the intervention.
Secondary outcome [6] 325723 0
Fasting blood glucose (mmol/L)
Blood tests were performed at the Storr Liver Unit at Westmead Hospital following a 12 hour overnight fast. All blood tests were performed in the morning, between 7.30am and 10.00am. Patients were allowed to take their usual morning medications. All biochemical tests were performed using a conventional automated analyser in the Department of Pathology, Westmead Hospital.
Timepoint [6] 325723 0
Baseline and 3, 6, 12, 18 and 24 months post commencement of the intervention.
Secondary outcome [7] 325724 0
Fasting insulin (mU/L)
Blood tests were performed at the Storr Liver Unit at Westmead Hospital following a 12 hour overnight fast. All blood tests were performed in the morning, between 7.30am and 10.00am. Patients were allowed to take their usual morning medications. All biochemical tests were performed using a conventional automated analyser in the Department of Pathology, Westmead Hospital.
Timepoint [7] 325724 0
Baseline and 3, 6, 12, 18 and 24 months post commencement of the intervention.
Secondary outcome [8] 325725 0
Ferritin (ug/L)
Blood tests were performed at the Storr Liver Unit at Westmead Hospital following a 12 hour overnight fast. All blood tests were performed in the morning, between 7.30am and 10.00am. Patients were allowed to take their usual morning medications. All biochemical tests were performed using a conventional automated analyser in the Department of Pathology, Westmead Hospital.
Timepoint [8] 325725 0
Baseline and 3, 6, 12, 18 and 24 months post commencement of the intervention.
Secondary outcome [9] 325726 0
2 hour insulin (mU.L)
At assessment points when an oral glucose tolerance test (OGTT) was required, participants were provided with a referral form to an external laboratory
Timepoint [9] 325726 0
Baseline and 3, 6, 12, 18 and 24 months post commencement of the intervention.
Secondary outcome [10] 325728 0
Total Cholesterol (mmol/L)
Blood tests were performed at the Storr Liver Unit at Westmead Hospital following a 12 hour overnight fast. All blood tests were performed in the morning, between 7.30am and 10.00am. Patients were allowed to take their usual morning medications. All biochemical tests were performed using a conventional automated analyser in the Department of Pathology, Westmead Hospital.
Timepoint [10] 325728 0
Baseline and 3, 6, 12, 18 and 24 months post commencement of the intervention.
Secondary outcome [11] 325729 0
Triglyceride (mmol/L)
Blood tests were performed at the Storr Liver Unit at Westmead Hospital following a 12 hour overnight fast. All blood tests were performed in the morning, between 7.30am and 10.00am. Patients were allowed to take their usual morning medications. All biochemical tests were performed using a conventional automated analyser in the Department of Pathology, Westmead Hospital.
Timepoint [11] 325729 0
Baseline and 3, 6, 12, 18 and 24 months post commencement of the intervention.
Secondary outcome [12] 325730 0
Total kilojoule intake (per day)
Participants completed an interview-based diet history and food frequency questionnaire administered by a dietitian and a 3-day food record at each time point.
Timepoint [12] 325730 0
Baseline and 3, 6, 12, 18 and 24 months post commencement of the intervention.
Secondary outcome [13] 325731 0
Cardiorespiratory fitness (VO2) (ml/kg/min)
To corroborate the data obtained from the physical activity questionnaire, half the study group (n=69) undertook a sub-maximal aerobic assessment at baseline and 3 months to determine cardiorespiratory fitness (VO2). The assessment used a cycle ergometer and was administered by exercise physiologists using the YMCA protocol (32).
Timepoint [13] 325731 0
Baseline and 3, 6, 12, 18 and 24 months post commencement of the intervention.

Eligibility
Key inclusion criteria
Diagnosis of non-aldoholic fatty liver disease (NAFLD) or hepatitis C (and not receiving anti-viral therapy)
Males and females aged 18 years and over
Elevated ALT U/L) (>30 in males and >19 in females)


Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Alcohol intake >30g per day in males or >20g per day in females
Current injecting drug use or unstable drug habit
Liver cancer
Severe Depression (HADDS Score)
Cushing's Syndrome
Chronic Pancreatitis
Other liver diseases identified by appropriate tests including Hepatitis B (negative for hepatitis B surface antigen), autoimmune liver disease (antinuclear antibody, antismooth muscle antibody, anti-liver kidney microsomal antibody and antimitochondrial antibody), Wilson's disease (serum copper and ceruloplasmin levels), alpha-1 antitrypsin deficiency (alpha-1 antitrypsin deficiency (alpha-1 antitrypsin levels and alpha-1 antitrypsin genotype) and hemochromatosis (iron studies and genotyping for C268Y and H63D mutations).

Study design
Purpose of the study
Educational / counselling / training
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Once eligibility was established, a sealed envelope was opened, revealing the group to which the participant had been allocated. Opening of randomisation envelopes and allocation to intervention group was done with more than one staff member present. The group to which each eligible participant was randomised was documented at the time the envelope was opened along with the names of the staff members present at the time of randomisation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants had a 25% chance of being allocated to each of the four study groups. A statistician used a computer program to generate the randomisation lists.. A staff member not involved in delivering the intervention wrote the group allocation according to randomisation number on a piece of paper and placed each in a sealed envelope.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
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
Recruitment hospital [1] 6172 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 13604 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 294062 0
Government body
Name [1] 294062 0
National Health and Medical Research Council
Address [1] 294062 0
National Health and Medical Research Council (NHMRC)
GPO Box 1421 Canberra ACT 2601
Country [1] 294062 0
Australia
Primary sponsor type
Individual
Name
Professor Jacob George
Address
Storr Liver Unit
Westmead Millenium Research Institute
176 Hawkesbury Rd, Westmead NSW 2145

Country
Australia
Secondary sponsor category [1] 292893 0
University
Name [1] 292893 0
University of Sydney
Address [1] 292893 0
Faculty of Medicine
Western Clinical School
Westmead Hospital
Darcy Rd Westmead
2145 NSW
Country [1] 292893 0
Australia
Secondary sponsor category [2] 292894 0
Other
Name [2] 292894 0
Westmead Millennium Institute
Address [2] 292894 0
Westmead Hospital
Darcy Rd
Westmead
2145 NSW
Country [2] 292894 0
Australia
Other collaborator category [1] 279082 0
Individual
Name [1] 279082 0
Professor Adrian Bauman
Address [1] 279082 0
Prevention Research Collaboration, School of Public Health, Charles Perkins Centre (D17), University of Sydney, Sydney, NSW 2006, Australia.
Country [1] 279082 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295494 0
University of Sydney Human Research Ethics Committee
Ethics committee address [1] 295494 0
Margaret Telfer Building (K07)
University of Sydney
NSW 2006
Ethics committee country [1] 295494 0
Australia
Date submitted for ethics approval [1] 295494 0
01/09/2004
Approval date [1] 295494 0
01/10/2004
Ethics approval number [1] 295494 0
Ethics committee name [2] 295495 0
Western Sydney Area Health Service Human Ethics Committee
Ethics committee address [2] 295495 0
Western Sydney Local Health District Office
Institute Rd
Westmead NSW 2145
Ethics committee country [2] 295495 0
Australia
Date submitted for ethics approval [2] 295495 0
01/09/2004
Approval date [2] 295495 0
01/10/2004
Ethics approval number [2] 295495 0

Summary
Brief summary
The aim of this study was to assess the effect of a lifestyle intervention based on behaviour change theories on liver enzymes and metabolic abnormalities in patients diagnosed with Non-alcoholic fatty liver disease (NAFLD) or Hepatitis C and not receiving anti-viral therapy.
We hypothesised that if successful; such an intervention would reduce the metabolic risk profile of patients and thereby lead to a reduction in the drivers of hepatic steatosis and inflammation.
Trial website
Trial related presentations / publications
St. George, A., Bauman, A., Johnston, A., Farrell, G., Chey, T., & George, J. (2009). Independent effects of physical activity in patients with nonalcoholic fatty liver disease. Hepatology, 50(1), 68-76.

St. George, A., Bauman, A., Johnston, A., Farrell, G., Chey, T., & George, J. (2009). Effect of a lifestyle intervention in patients with abnormal liver enzymes and metabolic risk factors. Journal of Gastroenterology and Hepatology, 24(3), 399-407.
.
Public notes

Contacts
Principal investigator
Name 67350 0
Prof Jacob George
Address 67350 0
Westmead Millennium Institute for Medical Research
Storr Liver Unit
Westmead Hospital, Darcy Rd
Westmead NSW 2145

Country 67350 0
Australia
Phone 67350 0
+61 2 9845 7705
Fax 67350 0
+61 2 9845 6280
Email 67350 0
jacob.george@sydney.edu.au
Contact person for public queries
Name 67351 0
Prof Jacob George
Address 67351 0
Westmead Millennium Institute for Medical Research
Storr Liver Unit
Westmead Hospital, Darcy Rd
Westmead NSW 2145
Country 67351 0
Australia
Phone 67351 0
+61 2 9845 7705
Fax 67351 0
+61 2 9845 6280
Email 67351 0
jacob.george@sydney.edu.au
Contact person for scientific queries
Name 67352 0
Prof Jacob George
Address 67352 0
Westmead Millennium Institute for Medical Research
Storr Liver Unit
Westmead Hospital, Darcy Rd
Westmead NSW 2145
Country 67352 0
Australia
Phone 67352 0
+61 2 9845 7705
Fax 67352 0
+61 2 9845 6280
Email 67352 0
jacob.george@sydney.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary