ANZCTR - Registration

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

Trial registered on ANZCTR

Registration number

ACTRN12617001476325

Ethics application status

Approved

Date submitted

16/10/2017

Date registered

19/10/2017

Date last updated

25/03/2021

Date data sharing statement initially provided

25/03/2021

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]

Nil known

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Type 2 diabetes

Gestational diabetes

overweight or obese

Condition category

Condition code

Diet and Nutrition

Obesity

Metabolic and Endocrine

Diabetes

Reproductive Health and Childbirth

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 diet checklists, weigh the participant and answer any questions. Weight will be taken at every visit. CSIRO Healthy Eating Score survey and a physical activity survey (Active Australia survey) and a sleep quality questionnaire (Pittsburgh Sleep Quality index) will be administered at baseline, 3, 6 and 12 months. Fasting blood samples will be taken on three occasions (baseline, 3 and 12 months) and will test fasting glucose, fasting insulin. HbA1C and fasting glucose will be measured by finger prick analysis at baseline, 3, and 12 months . A 2-hr oral glucose tolerance test (OGTT) will also be administered at baseline and 12 months, this will be done by using whole capillary blood via finger prick analysis with a glucometer.
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]

Lifestyle

Intervention code [2]

Behaviour

Intervention code [3]

Treatment: Other

Comparator / control treatment

Participants will follow a continuous energy restriction diet (CER) over the 12 month study. They will be allowed 6000 kJ (1500kCal) 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]

Weight loss measured on digital scales.

Timepoint [1]

Baseline, 1,2,3, 6, 9 and 12 months (12 months primary timepoint)

Secondary outcome [1]

2 hour glucose tolerance measured from a fasting 2-hr 75g oral glucose tolerance test taken by capillary whole blood finger-prick analysis at 0, 60 and 120 minute

Timepoint [1]

Baseline, 12 months

Secondary outcome [2]

HbA1C measured using a HbA1c point of care machine.

Timepoint [2]

Baseline, 3 and 12 months

Secondary outcome [3]

Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) calculated from fasting glucose and fasting insulin blood sample tests.

Timepoint [3]

Baseline, 3 and 12 months

Secondary outcome [4]

Change in quality of dietary intake measured from the CSIRO Healthy Diet Score online survey

Timepoint [4]

Baseline, 3, 6 and 12 months

Secondary outcome [5]

Fasting glucose taken from blood sample and capillary whole blood

Timepoint [5]

Baseline, 3 and 12 months

Secondary outcome [6]

Fasting insulin taken from venous blood sample

Timepoint [6]

Baseline, 3 and 12 months

Secondary outcome [7]

Change in Body Mass Index
BMI was calculated from height and weight using the equation BMI=[weight(kg) / height(m2)].
Height was measured at the baseline visit without shoes on using a wall-mounted stadiometer and recorded to the nearest 0.1cm. Body weight was measured at each visit in light clothing without shoes using calibrated electronic digital scales and recorded to the nearest 0.1kg.

Timepoint [7]

0, 3 and 12 months

Eligibility

Key inclusion criteria

- Age 18 years or over
- Diagnosed with gestational diabetes (GDM) by a medical professional during a pregnancy
- BMI greater than or equal to 25kg/m2
- Not taking any diabetes medication including metformin

Minimum age

18 Years

Maximum age

No limit

Sex

Females

Can healthy volunteers participate?

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
-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 years since GDM (=5 years and > 5 years) and BMI (<30kg/m2 and =30kg/m2). . 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 80% power, significance set at 5% and allowing for 50% drop out rate 141 participants would be needed.

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.. Participants will be stratified according to BMI 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

Completed

Date of first participant enrolment

Anticipated

15/01/2018

Actual

16/03/2018

Date of last participant enrolment

Anticipated

29/06/2018

Actual

19/11/2018

Date of last data collection

Anticipated

5/07/2019

Actual

22/11/2019

Sample size

Target

141

Accrual to date

Final

121

Recruitment in Australia

Recruitment state(s)

Funding & Sponsors

Funding source category [1]

University

Name [1]

University of South Australia

Address [1]

School of Pharmacy and Medical Sciences
GPO Box 2471 Adelaide SA 5000

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

University of South Australia Human Ethics Committee

Ethics committee address [1]

GPO Box 2471, Adelaide SA 5001

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

11/10/2017

Approval date [1]

13/10/2017

Ethics approval number [1]

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

Mrs Kristy Gray

Address

University of South Australia
GPO Box 2471, Adelaide SA 5001

Country

Australia

Phone

+61435022121

Fax

[email protected]

Contact person for public queries

Name

Jennifer Keogh

Address

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

Australia

Phone

+61 8 83022579

Fax

+61 8 8302 2389

[email protected]

Contact person for scientific queries

Name

Jennifer Keogh

Address

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

Australia

Phone

+61 8 83022579

Fax

+61 8 8302 2389

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

No IPD data will be available for this trial as this was not approved by ethics.

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	The effect of intermittent energy restriction on weight loss and diabetes risk markers in women with a history of gestational diabetes: a 12-month randomized control trial.	2021	https://dx.doi.org/10.1093/ajcn/nqab058

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Registering a new trial?

Documents added manually

Documents added automatically