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Trial registered on ANZCTR


Registration number
ACTRN12617001476325
Ethics application status
Approved
Date submitted
16/10/2017
Date registered
19/10/2017
Date last updated
6/04/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of intermittent energy restriction (5:2 diet) on weight loss and risk of type 2 diabetes in women who have had gestational diabetes.
Scientific title
The effect of intermittent energy restriction on weight loss and diabetes risk markers in women who have had gestational diabetes.
Secondary ID [1] 293137 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 diabetes 305108 0
Gestational diabetes 305109 0
overweight or obese 305110 0
Condition category
Condition code
Diet and Nutrition 304419 304419 0 0
Obesity
Metabolic and Endocrine 304420 304420 0 0
Diabetes
Reproductive Health and Childbirth 304444 304444 0 0
Fetal medicine and complications of pregnancy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A 12 month randomised control study will be conducted. Participants randomised to the intermittent energy restriction (IER) group will be required to follow a very low energy diet of 2100kJ (500kCal) for two days per week and allowed ad libitum eating for the other five days per week. They may choose any days of the week for their ‘fasting’ days based on their individual preferences and will be encouraged to eat sensibly on their non-fasting days. Participants will receive education and written information developed by the study Dietitian on how to adhere to the fasting days, information on calorie content of foods and sample meal plans for the 2100kJ days also developed by the study Dietitian. Women who are breastfeeding will be allowed extra calorie allowance of up to 2100kJ per day to allow for the energy cost of human milk production and the study dietitian will advise protein intake of 67g per day, adequate hydration and advise that fasting days must not be consecutive. Additionally, breastfeeding mothers will be required to weigh themselves weekly (scales will be provided) to ensure that weight loss does not exceed 0.5kg per week. These participants will have fortnightly follow up with the study Dietitian via phone call, email or university visit if needed for the first 3 months then a minimum of monthly follow up through email, phone call or university visit while they continue to breastfeed. Phone calls or visits would take between five and fifteen minutes.
Participants will attend the clinic on 7 occasions over the 12 months (baseline, 1, 2 3,6, 9 and 12 months). At each visit they will be seen by the study dietitian who will check their compliance with the diet through weighed food diaries and diet checklists, weigh the participant and answer any questions. They will also receive email follow up monthly for the first 3 months (2, 6 and 10 weeks) then every six weeks for the remainder of the study (4.5, 7.5 and 10.5 months). Weight will be taken at every visit. CSIRO Healthy Eating Score survey and a physical activity survey (Active Australia survey) will be administered at baseline, 3, 6 and 12 months. Fasting blood samples will be taken on five occasions (baseline, 3, 6, 9 and 12 months) and will test fasting glucose, fasting insulin, HbA1C and lipids. A 2-hr oral glucose tolerance test (OGTT) will also be administered at baseline and 12 months.
Visits to the clinic at baseline and 12 months will take between 2.25 and 2.5 hours due to the 2 hour OGTT. All other visits (1,2,3,6 and 9 months) will take 15-20 minutes.
Women who achieve a weight loss of 7% of their body weight or reach a BMI of 21kg/m2 will be asked to maintain their body weight and be given advice on how to do this. Participants will be encouraged to meet physical activity recommendations of 30 minutes moderate physical activity per day on most days of the week.
Intervention code [1] 299387 0
Lifestyle
Intervention code [2] 299396 0
Behaviour
Intervention code [3] 299397 0
Treatment: Other
Comparator / control treatment
Participants will follow a continuous energy restriction diet (CER) over the 12 month study. They will be allowed 5500 kJ (1300kCal) each day. They will be given education on how to adhere to their diet, verbal and written information on the calorie content of various foods and sample meal plans. They will be encouraged to consume a healthy diet to make up their daily calorie allowance and limit consumption of discretionary foods and drinks. The diet materials are developed by the study Dietitian and based on the CSIRO Total Wellbeing Diet. Breastfeeding women will be allowed up to an extra 2100kJ per day as per the IER group and will be required to weigh themselves weekly to ensure weight loss does not exceed 0.5kg per week. All visits, tests and procedures will be the same for the CER group as the IER group for both breastfeeding and non breastfeeding women.
Control group
Active

Outcomes
Primary outcome [1] 303657 0
Weight loss measured on digital scales.
Timepoint [1] 303657 0
Baseline, 1,2,3, 6, 9 and 12 months (12 months primary timepoint)
Primary outcome [2] 303687 0
Change in body mass index measured as (weight in kg / height in metres squared)
Timepoint [2] 303687 0
Baseline, 1,2,3,6,9 and 12 months (12 months primary timepoint)
Secondary outcome [1] 339801 0
2 hour glucose tolerance measured from a fasting 2-hr 75g oral glucose tolerance test.
Timepoint [1] 339801 0
Baseline, 12 months
Secondary outcome [2] 339802 0
HbA1C measured using a HbA1c point of care machine.
Timepoint [2] 339802 0
Baseline, 3,6,9 and 12 months
Secondary outcome [3] 339804 0
Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) calculated from fasting glucose and fasting insulin blood sample tests.
Timepoint [3] 339804 0
Baseline, 3,6,9 and 12 months
Secondary outcome [4] 339805 0
Blood lipids measured via blood sample
Timepoint [4] 339805 0
Baseline, 3,6,9 and 12 months
Secondary outcome [5] 339806 0
Change in quality of dietary intake measured from the CSIRO Healthy Diet Score online survey
Timepoint [5] 339806 0
Baseline, 3, 6 and 12 months
Secondary outcome [6] 339851 0
Fasting glucose taken from blood sample
Timepoint [6] 339851 0
Baseline, 3,6,9 and 12 months
Secondary outcome [7] 339852 0
Fasting insulin taken from blood sample
Timepoint [7] 339852 0
Baseline,3,6,9 and 12 months

Eligibility
Key inclusion criteria
- Age 18 years or over
- Diagnosed with gestational diabetes (GDM) by a medical professional during a pregnancy within the last 5 years
- BMI greater than or equal to 25kg/m2
- Not taking any diabetes medication including metformin
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- Diagnosed with diabetes either prior to their GDM pregnancy or have developed diabetes since their GDM pregnancy.
- Pregnant or less than 12 weeks post partum
- Previous surgery for weight loss
- Participating in any other diets or clinical studies involving medical or lifestyle interventions
- Have been following the 5:2 diet in the last 3 months
- non-English speaking
- Previous or current diagnosis of an eating disorder
- Any other significant illness or disease

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)
Following initial contact with the university potential subjects will be screened and randomly allocated to one of the arms of the study. Participants will be stratified according to BMI and age before randomisation. A random number block randomization will be used. Allocation is not concealed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised random balanced number sequence generator (randomization.com)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
A non inferiority power calculation was conducted to determine the sample size needed for the study to identify if a difference does exist between the intervention and control groups using weight loss as the primary outcome. With 90% power and significance set at 5%, 130 participants would be needed. To allow for a potential dropout rate of up to 20%, we will aim to recruit a total of 156 participants for the trial (n=78 for each group).

Data tabulation and descriptive analysis of all independent and dependent variables will be conducted. Summary statistics, such as means, variances, and standard deviations, will be reported for each variable. Data will be tested for normal distribution using Q-Q plots and Kolomogorov-Smivov tests. Pearson’s chi-squared tests for categorical variables, and independent t-tests or Wilcoxon rank sum for continuous variables will compare differences between intervention and control groups at baseline and over time for weight, BMI, fasting glucose, 2-hr glucose, HbA1C, insulin resistance and HOMA-IR, dietary intake and lipids. Participants will be stratified according to age and weight and for the intervention studies an intention-to-treat method of analysis will be adhered to. Statistical significance will be set to p<0.05.

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)
SA

Funding & Sponsors
Funding source category [1] 297762 0
University
Name [1] 297762 0
University of South Australia
Address [1] 297762 0
School of Pharmacy and Medical Sciences
GPO Box 2471 Adelaide SA 5000
Country [1] 297762 0
Australia
Primary sponsor type
University
Name
University of South Australia
Address
School of Pharmacy and Medical Sciences
GPO Box 2471 Adelaide SA 5000
Country
Australia
Secondary sponsor category [1] 296803 0
None
Name [1] 296803 0
Address [1] 296803 0
Country [1] 296803 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298825 0
University of South Australia Human Ethics Committee
Ethics committee address [1] 298825 0
GPO Box 2471, Adelaide SA 5001
Ethics committee country [1] 298825 0
Australia
Date submitted for ethics approval [1] 298825 0
11/10/2017
Approval date [1] 298825 0
13/10/2017
Ethics approval number [1] 298825 0
200165

Summary
Brief summary
In 2015 at least 10.9% of pregnant women in Australia were diagnosed with gestational diabetes (GDM) (1, 2). GDM creates risk of complications to both mother and baby during pregnancy, labour and delivery, and although GDM usually disappears shortly after birth, the mother remains at high risk for developing Type 2 Diabetes (T2DM) in the future (3). The health risks and complications associated with T2DM are well known and include development of other chronic diseases including cardiovascular disease (CVD), heart attack, stroke and kidney disease making diabetes a major health concern in Australia and globally (4). Lifestyle interventions involving diet and/or exercise that result in weight loss can reduce the risk of developing T2DM (5), however research has shown weight loss is not easily achieved or maintained (6-8). Keeping women engaged in a weight loss program can be difficult when they have a baby or young children to care for given the time constraints and lifestyle adjustments associated with looking after their children (9). Intermittent Energy Restriction (IER) is a form of calorie restriction which requires periods of severe calorie restriction or fasting) followed by periods of non-restricted eating each week. Previous research shows IER can result in weight loss at a comparable rate to daily energy restriction (10, 11).
This study will test if the IER diet strategy commonly known as ‘the 5:2 diet’ provides a suitable regime for women with a history of GDM who have a young family at home by creating less burden and interruption to daily life by restricting energy intake for short periods and advising usual but not excessive eating the rest of the week. This will be the first study that examines an IER pattern for weight loss and T2DM prevention following GDM. Results from this PhD have the potential to benefit Australian women and families by improving their health and potentially reducing the financial burden associated with diabetes to individuals and the community.

References
1. National Diabetes Services Scheme. NDSS Data Snapshots December 2015 2015 [20/06/2017]. Available from: https://static.diabetesaustralia.com.au/s/fileassets/diabetes-australia/2fdff38c-078e-4e76-8dee-8a5bdcf07ae8.pdf.
2. Australian Bureau of Statistics. 3301.0 - Births, Australia, 2015, Summary of Statistics for Australia 2016 [Available from: http://www.abs.gov.au/ausstats/abs@.nsf/mf/3301.0.
3. Bellamy L, Casas JP, Hingorani AD, Williams D. Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis. Lancet (London, England). 2009;373(9677):1773-9.
4. Baker IDI Heart & Diabetes Institute, Diabetes Australia, Juvenile Diabetes Research Foundation. Diabetes: the silent pandemic and its impact on Australia. 2012:27.
5. Ratner RE, Christophi CA, Metzger BE, Dabelea D, Bennett PH, Pi-Sunyer X, et al. Prevention of diabetes in women with a history of gestational diabetes: effects of metformin and lifestyle interventions. The Journal of clinical endocrinology and metabolism. 2008;93(12):4774-9.
6. Morton S, Kirkwood S, Thangaratinam S. Interventions to modify the progression to type 2 diabetes mellitus in women with gestational diabetes: a systematic review of literature. Current opinion in obstetrics & gynecology. 2014;26(6):476-86.
7. Guo J, Chen J-L, Whittemore R, Whitaker E. Postpartum lifestyle interventions to prevent type 2 diabetes among women with history of gestational diabetes: A systematic review of randomized clinical trials. J Women's Health. 2016;25(1):38-49.
8. Peacock AS, Bogossian F, McIntyre HD, Wilkinson S. A review of interventions to prevent type 2 diabetes after gestational diabetes. Journal of the Australian College of Midwives. 2014;27(4):e7-e15.
9. Amorim AR, Linne YM, Lourenco PM. Diet or exercise, or both, for weight reduction in women after childbirth. Cochrane Database Syst Rev. 2007(3):Cd005627.
10. Davis CS, Clarke RE, Coulter SN, Rounsefell KN, Walker RE, Rauch CE, et al. Intermittent energy restriction and weight loss: a systematic review. Eur J Clin Nutr. 2016;70(3):292-9.
11. Headland M, Clifton PM, Carter S, Keogh JB. Weight-loss outcomes: A systematic review and meta-analysis of intermittent energy restriction trials lasting a minimum of 6 months. Nutrients. 2016;8(6):08.

Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 78354 0
Mrs Kristy Gray
Address 78354 0
University of South Australia
GPO Box 2471, Adelaide SA 5001
Country 78354 0
Australia
Phone 78354 0
+61435022121
Fax 78354 0
Email 78354 0
kristy.gray@mymail.unisa.edu.au
Contact person for public queries
Name 78355 0
A/Prof Jennifer Keogh
Address 78355 0
School of Pharmacy and Medical Sciences, University of South Australia
Office: P1-23 Playford Building City East Campus
Postal address: GPO Box 2471 Adelaide SA 5000
Country 78355 0
Australia
Phone 78355 0
+61 8 83022579
Fax 78355 0
+61 8 8302 2389
Email 78355 0
jennifer.keogh@unisa.edu.au
Contact person for scientific queries
Name 78356 0
A/Prof Jennifer Keogh
Address 78356 0
School of Pharmacy and Medical Sciences, University of South Australia
Office: P1-23 Playford Building City East Campus
Postal address: GPO Box 2471 Adelaide SA 5000
Country 78356 0
Australia
Phone 78356 0
+61 8 83022579
Fax 78356 0
+61 8 8302 2389
Email 78356 0
jennifer.keogh@unisa.edu.au

No data has been provided for results reporting
Summary results
Not applicable