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Trial registered on ANZCTR


Registration number
ACTRN12619000997156
Ethics application status
Approved
Date submitted
6/08/2018
Date registered
12/07/2019
Date last updated
12/07/2019
Date data sharing statement initially provided
12/07/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Non-Alcoholic Fatty Liver Disease (NAFLD): the feasibility of two different weight loss dietary approaches
Scientific title
Non-Alcoholic Fatty Liver Disease (NAFLD): the feasibility of two different weight loss dietary approaches
Secondary ID [1] 291104 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Nonalcholic fatty liver disease (NAFLD) 301928 0
Overweight 301929 0
Obesity 309489 0
Condition category
Condition code
Oral and Gastrointestinal 301583 301583 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Diet and Nutrition 301584 301584 0 0
Other diet and nutrition disorders
Diet and Nutrition 301585 301585 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a 6 month feasibility study. The feasibility and acceptability of two different weight loss dietary approaches will be examined. Diet A will utilise partial meal replacements (Optifast). Diet B will be provided wtih dietitian delivered dietary advice based on the 2004 recommendations for the treatment and prevention of diabetes mellitus published by the Diabetes and Nutrition Study Group of the European Association for the Study of Diabetes. The dietary treatment goal for all participants will be a 5-10% weight loss over 6 months.

Diet A Group (Partial meal replacement)
The rate of weight loss will be 1.0kg/week, and no more than 1.5kg/week for 4 weeks, then 0.5-1.0kg/week until weight loss goal is achieved.
Participants in the Diet A group will be given partial meal replacements (Optifast) and suggested meal plans for 8 weeks by a dietitian. Partial rather than full meal replacement will be used. A gradual weight loss of <1.6 kg/week) is advisable, rather than more rapid loss, because faster weight loss is known to exacerbate liver injury.
For the first four weeks 2 meals per day will be replaced with an Optifast product, followed by one meal replaced by Optifast per day for a further four weeks. From week 8 no Optifast products will be used but participants will be instructed to consume an individualised low calorie diet for the subsequent 18 weeks, until 6 months.
During weeks 1-4, in addition to two Optifast meal replacements per day, the daily diet will include a light meal (500 Cal/2090 kJ), 2 pieces fruit, 1 serve low-fat dairy (250ml low fat milk, 40g/ 2 slices low fat cheese or 200g low fat yoghurt), 2 cups low starch vegetables, and 2 litres water.
During weeks 5-8, in addition to one Optifast meal replacement per day, the daily diet will include a light breakfast (350 Cal/1463 kJ), one light meal (500 Cal/2090 kJ), 2 pieces of fruit, 1 serve low-fat dairy (250ml low fat milk, 40g/ 2 slices low fat cheese or 200g low fat yoghurt), 2 cups low starch vegetables, and 2 litres water.
Education about healthy eating habits and low calorie meals and snacks will be included and reinforced at all appointments with the dietitian.
Participants in this group will see a dietitian weekly during weeks 1-8. They will then see a nurse for ‘weigh-ins’ fortnightly for 1 month, then monthly for months 4-6.
3-day weighed diet records at baseline and 8 weeks will guide dietary advice. Dietary adherence will be monitored by the study dietitian enquiring about Optifast products consumed, and collecting empty Optifast product packages and by asking participant to complete a daily food diary. Change in body weight (kilograms) and % of liver fat as measured by Hydrogen Magnetic Resonance Spectroscopy (H-MRS) will be measured.

Diet B Group (Treatment and prevention of diabetes dietary recommendations)
The rate of weight loss will be 0.5-1.0kg/week until weight loss goal is achieved.
Participants in the Diet B group will be provided with dietary advice based on evidence-based recommendations for the treatment and prevention of diabetes mellitus published by the Diabetes and Nutrition Study Group of the European Association for the Study of Diabetes (2004). The aim will be to achieve a gradual, but sustainable weight loss through dietary changes.
Appropriate food quantities, vegetables, fruit, legumes, wholegrain cereals, fish (preferably oily), nuts, low fat dairy products and appropriate fats and oils will be emphasised. Dietary advice will be tailored to the individual taking into account culture, family, employment, budget and co-morbidities. We have previously successfully used this dietary approach in the Lifestyle Over and Above Drugs in Diabetes (LOADD) study which included patients with type 2 diabetes who had poor glucose control despite taking recommended hypoglycaemic medication.
Participants in this group will see a dietitian weekly during weeks 1-8, then fortnightly for 1 month, monthly for months 4-6. They will also be weighed at each of these visits.
3-day weighed diet records at baseline and 8 weeks will guide dietary advice. Dietary adherence will be assessed by reviewing paricipant dietary goals and undertaking a diet recall at each visit. Change in body weight (kilograms) and % of liver fat as measured by Hydrogen Magnetic Resonance Spectroscopy (H-MRS) will be measured.

All participants in both diet groups will be given one-off Ministiry of Health standard pamphlet, ‘Be active every day: Physical activity for adults’ exercise advice, with the aim of doing at least 30 minutes of moderate intensity physical activity most, if not, all days of the week.
Intervention code [1] 297665 0
Lifestyle
Intervention code [2] 297666 0
Behaviour
Intervention code [3] 297667 0
Treatment: Other
Comparator / control treatment
This is a feasibility study to determine the ACCEPTABILITY of EACH of the two different weight loss dietary approaches (described above) to determine if Diet A or Diet B is more acceptable than the other prior to undertaking a randomised controlled trial. This feasibility study is looking at whether participants like their allocated dietary approach, and how well participants adhere to each of the dietary approaches.
Control group
Active

Outcomes
Primary outcome [1] 301640 0
Change in body weight (kilograms) as measured by calibrated Wedderburn Tanita weighing scales
Timepoint [1] 301640 0
Baseline and at 6 months after dietary intervention commencement.
Primary outcome [2] 301641 0
Change in % of liver fat as measured by Hydrogen Magnetic Resonance Spectroscopy (H-MRS).
Timepoint [2] 301641 0
Baseline and at 6 months after dietary intervention commencement.
Secondary outcome [1] 333400 0
Waist circumference (centrimetres) as measured at the midpoint between the lower rib margin and the iliac crest with a tape measure.
Timepoint [1] 333400 0
Baseline and at 6 months after dietary intervention commencement.
Secondary outcome [2] 333401 0
Change in level of liver enzyme, alanine transaminase (ALT) as measured from blood serum sample.
Timepoint [2] 333401 0
Baseline and at 6 months after dietary intervention commencement.
Secondary outcome [3] 333402 0
Change in level of liver enzyme, aspartate transaminase (AST) as measured from blood serum sample.
Timepoint [3] 333402 0
Baseline and at 6 months after dietary intervention commencement.
Secondary outcome [4] 333403 0
Change in level of liver enzyme, gamma-glutamyl transferase (GGT) as measured from blood serum sample.
Timepoint [4] 333403 0
Baseline and at 6 months after dietary intervention commencement.
Secondary outcome [5] 338575 0
Change in diastolic blood pressure measured using Welch Allyn digital blood pressure monitor and cuff.
Timepoint [5] 338575 0
Baseline and at 6 months after dietary intervention commencement.
Secondary outcome [6] 338576 0
Change in systolic blood pressure measured using Welch Allyn digital blood pressure monitor and cuff.
Timepoint [6] 338576 0
Baseline and at 6 months after dietary intervention commencement.
Secondary outcome [7] 338577 0
Dietary adherence (3-day weighed diet record)
Timepoint [7] 338577 0
At 8 weeks and at completion of the six month dietary intervention.
Secondary outcome [8] 338578 0
Change in total cholesterol as measured from blood serum sample.
Timepoint [8] 338578 0
Baseline and at 6 months after dietary intervention commencement.
Secondary outcome [9] 338579 0
Change in HDL cholesterol as measured from blood serum sample.
Timepoint [9] 338579 0
Baseline and at 6 months after dietary intervention commencement.
Secondary outcome [10] 338580 0
Change in LDL cholesterol as measured from blood serum sample.
Timepoint [10] 338580 0
Baseline and at 6 months after dietary intervention commencement.
Secondary outcome [11] 338581 0
Change in triglycerides as measured from blood serum sample.
Timepoint [11] 338581 0
Baseline and at 6 months after dietary intervention commencement.
Secondary outcome [12] 338582 0
Change in free fatty acids as measured from blood serum sample.
Timepoint [12] 338582 0
Baseline and at 6 months after dietary intervention commencement.
Secondary outcome [13] 338583 0
Change in ApoB as measured from blood serum sample.
Timepoint [13] 338583 0
Baseline and at 6 months after dietary intervention commencement.
Secondary outcome [14] 338585 0
Change in ApoA1 as measured from blood serum sample.
Timepoint [14] 338585 0
Baseline and at 6 months after dietary intervention commencement.
Secondary outcome [15] 338586 0
Change in lipoprotein (a) as measured from blood serum sample.
Timepoint [15] 338586 0
Baseline and at 6 months after dietary intervention commencement.
Secondary outcome [16] 338587 0
Change in urate as measured from blood serum sample.
Timepoint [16] 338587 0
Baseline and at 6 months after dietary intervention commencement.
Secondary outcome [17] 338589 0
Urine albumin creatinine ratio
Timepoint [17] 338589 0
Baseline and at 6 months after dietary intervention commencement.
Secondary outcome [18] 338590 0
Change in fatty liver index (FLI)
[FLI = (e 0.953*loge (triglycerides) + 0.139*BMI + 0.718*loge (ggt) + 0.053*waist circumference - 15.745) / (1 + e 0.953*loge (triglycerides) + 0.139*BMI + 0.718*loge (ggt) + 0.053*waist circumference - 15.745) * 100]
Timepoint [18] 338590 0
Baseline and at 6 months after dietary intervention commencement.
Secondary outcome [19] 338591 0
Change in NAFLD liver fat score as calculated by the formular shown below.
[NAFLD liver fat score = -2.89 + 1.18 x metabolic syndrome (yes = 1/no = 0) + 0.45 x type 2 diabetes (yes = 2/no = 0) + 0.15 x fS-insulin (mU/L) + 0.04 x fS-AST (U/L) - 0.94 x AST/ALT] (type 2 diabetes determined by HbA1c as measured from blood serum sample. Insulin, AST and ALT as measured from blood serum sample.)
Timepoint [19] 338591 0
Baseline and at 6 months after dietary intervention commencement.
Secondary outcome [20] 365185 0
Acceptability rating of dietary approaches as measured by acceptability questionnaire. This was based on the acceptability questionnaire used by Barnard et al. (2016) "Acceptability of a Therapeutic Low-Fat, Vegan Diet in Premenopausal Women" and specifically modified for this study.
Timepoint [20] 365185 0
6 months after dietary intervention commencement.

Eligibility
Key inclusion criteria
• NAFLD defined using the 2012 American Diagnosis and Management of Non-alcoholic Fatty Liver Disease Practice Guidelines (In summary, a diagnosis of NAFLD requires evidence of hepatic steatosis either by imaging or histology, and no causes for secondary hepatic fat accumulation (e.g. excess alcohol intake, hepatitis B or C).
• Dunedin resident men and women
• aged 20-65 years
• overweight or obese (BMI greater than or equal to 25kg/m2)
Minimum age
20 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• patients with type 1 diabetes
• patients with type 2 diabetes using insulin
• those with a terminal illness
• pregnant women
• lactating women
• those unwilling to attempt to comply with intensive dietary advice
• any contraindications to having magnetic resonance scanning including claustrophobia

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)
Allocation is not concealed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be stratified based on:
• Sex – male/female
• Diabetes status according to inclusion and exclusion criteria. [The people with diabetes included in study will be those witih type 2 diabetes NOT treated with insulin] – yes/no

Participants will be randomised to one of the following weight loss dietary approaches treatments:
1= Diet A (partial meal replacements using Optifast followed by nurse weigh-ins)
2= Diet B (dietitian delivered dietary advice based on the 2004 recommendations for the treatment and prevention of diabetes mellitus published by the Diabetes and Nutrition Study Group of the European Association for the Study of Diabetes)

Randomisation process
1. Two sequences with the two diet options will be created: 12 and 12. These two sequences will be randomly ordered by pulling each out of a hat one by one. When each sequence is pulled from the hat, it will be inserted into a numbered brown paper envelope and sealed. The brown envelopes will not have windows, and will be numbered sequentially from 1 to 2. This will be repeated and numbered 3 and 4 and so on until there are 10 envelopes for each group.
2. When participants are recruited they will be grouped according to their sex and diabetes status:
• Males with diabetes (MD)
• Males without diabetes (MnD)
• Females with diabetes (FD)
• Females without diabetes (FnD)
When a group reaches at least two participants, the participants will be randomised in order of the first recruited onwards.
3. For each group of two a coin will be flipped, a “head” will be the next even numbered envelope and a “tail” will be the next odd numbered envelope. The numbered brown envelope correlating to the next even or odd number will be selected. The two participants in the group will be randomised by the sequence order in that envelope.
For example: When two males with diabetes are recruited, a coin will be flipped. If it is a “tail” the envelope numbered “1” will be selected. If the sequence in envelope 1 is “21”, the first male will be assigned to “Diet B” and the second to “Diet A”.
4. If there is a single participant remaining in any category randomisation will be performed as above but just the first treatment group listed will be assigned.
For example: If three men with diabetes were recruited by the completion of recruitment, the first two men will be randomised as above. The last man recruited will be randomised by flipping a coin again. If the dice number is a “heads” the envelope numbered “2” will be selected. If the sequence in envelope 2 is “12”, the man will be assigned to Diet A.
5. The randomisation group, participant’s full name and study code along with the date will be recorded in the randomisation file. The participant’s study codes and full names and date will also be recorded on the envelope and stored securely.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
This study focuses on the feasibility and acceptability of the two different weight loss dietary approaches, It also aims to confirm the standard deviations and correlation coefficient for the full study, Therefore, sample size calculations were not done for this pilot study. To determine the interventions are operationally sound we aim to recruit 10 participants per group or 20 participants in total. To account for dropout we aim to recruit 25 participants.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
29/01/2018
Date of last participant enrolment
Anticipated
Actual
31/05/2018
Date of last data collection
Anticipated
Actual
7/12/2018
Sample size
Target
25
Accrual to date
Final
20
Recruitment outside Australia
Country [1] 8772 0
New Zealand
State/province [1] 8772 0
Otago

Funding & Sponsors
Funding source category [1] 295544 0
University
Name [1] 295544 0
University of Otago
Country [1] 295544 0
New Zealand
Primary sponsor type
University
Name
University of Otago
Address
362 Leith St, North Dunedin, Dunedin 9016, New Zealand
Country
New Zealand
Secondary sponsor category [1] 294363 0
None
Name [1] 294363 0
Address [1] 294363 0
Country [1] 294363 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296865 0
Northern A Health and Disability Ethics Committee
Ethics committee address [1] 296865 0
Ethics committee country [1] 296865 0
New Zealand
Date submitted for ethics approval [1] 296865 0
31/05/2017
Approval date [1] 296865 0
18/07/2017
Ethics approval number [1] 296865 0
17/NTA/115

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

Contacts
Principal investigator
Name 72270 0
Dr Kirsten Coppell and A/Prof Michael Schultz
Address 72270 0
Dunedin Hospital
Department of Medicine
201 Great King St
Dunedin, 9016
New Zealand
Country 72270 0
New Zealand
Phone 72270 0
+64 3 470 9074
Fax 72270 0
Email 72270 0
kirsten.coppell@otago.ac.nz
Contact person for public queries
Name 72271 0
Kiri Sharp
Address 72271 0
Dunedin Hospital
Department of Medicine
201 Great King St
Dunedin, 9016
New Zealand
Country 72271 0
New Zealand
Phone 72271 0
+64 3 4740999 ext8514
Fax 72271 0
Email 72271 0
kiri.sharp@otago.ac.nz
Contact person for scientific queries
Name 72272 0
Kirsten Coppell
Address 72272 0
Dunedin Hospital
Department of Medicine
201 Great King St
Dunedin, 9016
New Zealand
Country 72272 0
New Zealand
Phone 72272 0
+64 3 470 9074
Fax 72272 0
Email 72272 0
kirsten.coppell@otago.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Undecided at this time until fully discussed with research team.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
2995Informed consent form  kirsten.coppell@otago.ac.nz
2996Study protocol  kirsten.coppell@otago.ac.nz



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.