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Trial registered on ANZCTR


Registration number
ACTRN12614001160628
Ethics application status
Approved
Date submitted
23/10/2014
Date registered
4/11/2014
Date last updated
6/08/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Pregnancy Outcomes after Pre-pregnancy weight loss in obese women (POP Study)
Scientific title
Does substantial pre-conception weight loss, achieved using a 12-week program of a Very Low Energy Diet, improve pregnancy outcomes compared to modest weight loss achieved using a diet and exercise program in obese women?
Secondary ID [1] 285535 0
Nil known
Universal Trial Number (UTN)
Trial acronym
POP Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obesity
 293352 0
Pre-pregnancy weight loss 293429 0
Condition category
Condition code
Diet and Nutrition 293626 293626 0 0
Obesity
Reproductive Health and Childbirth 293665 293665 0 0
Fetal medicine and complications of pregnancy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
12 week program which consists of:

1) Optifast meal replacement for 2 meals per day. The third meal consisting of a serve of protein (meat, chicken, egg, tofu approximately the size of the palm of the hand), 2 cups of non-starch vegetables and a salad dressed with oil. Patients will meet with a dietician at the start of the study for 30 minutes to discuss implementation of the diet. They will then prepare meals themselves. Participants will be seen every 2 weeks during the intervention phase. Blood pressure, weight, waist circumference and hip circumference will be measured.

2)Exercise according to national guidelines. Patients will be asked to complete the 'Australia Active Survey' prior to commencing the study. They will then be provided with an information booklet "Australia's Physical Activity and Sedentary Behaviour Guidelines for Adults". These guidelines recommend accumulating 150 to 300 minutes (2 ½ to 5 hours) of moderate intensity physical activity or 75 to 150 minutes (1 ¼ to 2 ½ hours) of vigorous intensity physical activity, or an equivalent combination of both moderate and vigorous activities each week. Subjects will be provided with a Pedometer (Yamax 700S). Daily step count will be recorded for 7 consecutive days (week 2 of study). This is for the purposes of ensuring there is not a significant difference in activity level between our two study groups.

3) Pre-pregnancy vitamin supplement including high dose folate. Folate 5mg orally, by mouth daily is recommended in accordance with the RANZCOG 'Obesity in Pregnancy' guidelines. In addition, participants will be asked to take a multi-vitamin suitable for a woman planning pregnancy (eg. Elevit).

Blood tests will be performed at the start and end of the intervention period. A food diary will be performed to ensure compliance with the diet. However, the amount of weight on on Optifast should be approximately 10-15% of body weight in 12 weeks based on the results of previous trials.

*Optifast products vary slightly but an example of the components of an Optifast product are listed below. Optifast products include soups, bars, desserts, shakes.

INGREDIENTS
Fructose glucose syrup (sugar beet), Soy crisp (Soy protein isolate, tapioca starch, salt), Milk chocolate (17%) [Sugar, Cocoa solids (6.5%), whole Milk powder, Emulsifier (Soy lecithin), Flavour], Soy nuts, Soy protein isolate, Minerals (Tripotassium citrate, Calcium phosphate, Sodium phosphate, Magnesium phosphate, Trisodium citrate, Magnesium carbonate, Ferric pyrophosphate, Potassium iodate, Zinc oxide, Sodium selenate, Copper sulphate, Manganese sulphate), Inulin, Fruit preparation [ Sugar, Raspberry (0.6%), Apple puree (0.4%),Raspberry (0.6%) and Cherry (0.2%) juice concentrate, Fructose syrup, Lactose (9%) (Milk), Vegetable fat, Flavour, Vegetable gum (440), Food acid (330)], Vegetable oil (Rapeseed), Vitamins (Ascorbic acid, Vitamin E acetate, Nicotinamide, Biotin, Vitamin A acetate, Calcium pantothenate, Folic acid, Cholecalciferol, Pyridoxine, Riboflavin, Thiamin, Cyanocobalamin), Food acid (330), Flavour, Emulsifier (Soy lecithin). Contains Milk and Soy. Made on equipment that also processes products containing tree nuts, peanuts and oats.

NUTRITIONAL INFORMATION
Servings per package 6
Serving size 60g

Unit of measure Quantity per serve
Energy kJ 950
Cal 228
Protein g 18.3
Fat, total g 6.9
- Saturated fat g 2.6
Carbohydrates g 20.8
- Sugar g 19.3
Dietary fibre g 4.5

VITAMINS
Thiamin mg 0.69
Riboflavin mg 1.02
Niacin mgNE 9.6
Pantothenic acid mg 1.9
Vit B6 mg 1
Biotin microgram 67
Folic Acid microgram 126
Vit C mg 63
Vit E mgTE 6

MINERALS
Sodium mg 390
Calcium mg 270
Copper mg 0.9
Iodine microgram 66
Iron mg 9.1
Magnesium mg 150
Manganese mg 0.70
Phosphorus mg 588
Selenium microgram 36
Zinc mg 5.4
Potassium mg 732
Intervention code [1] 290478 0
Prevention
Intervention code [2] 290506 0
Other interventions
Comparator / control treatment
12 week program based on the best practice care for an obese woman planning pregnancy which consists of :-

1) Diet according to the Australian Guide to Healthy Eating with a goal of weight loss. A 24 hour food recall will be performed with a dietician. The calorie content will then be calculated and a meal plan designed with the current calorie content minuss 500 calories per day. A food diary will then be completed and weight measured to ensure weight loss is achieved. Participants will be seen fortnightly during the intervention period. Blood pressure, weight, waist circumference and hip circumference will be measured.

2) Exercise according to national guidelines. Patients will be asked to complete the 'Australia Active Survey' prior to commencing the study. They will then be provided with an information booklet "Australia's Physical Activity and Sedentary Behaviour Guidelines for Adults". These guidelines recommend accumulating 150 to 300 minutes (2 ½ to 5 hours) of moderate intensity physical activity or 75 to 150 minutes (1 ¼ to 2 ½ hours) of vigorous intensity physical activity, or an equivalent combination of both moderate and vigorous activities, each week. Subjects will be provided with a Pedometer (Yamax 700S). Daily step count will be recorded for 7 consecutive days (week 2 of study). This is for the purposes of ensuring there is not a significant difference in activity level between our two study groups.

3) Pre-pregnancy vitamin supplement including high dose folate. Folate 5mg orally, by mouth daily is recommended in accordance with the RANZCOG 'Obesity in Pregnancy' guidelines. In addition, participants will be asked to take a multi-vitamin suitable for a woman planning pregnancy (eg. Elevit).

Blood tests will be performed at the start and end of the intervention period. A food diary will be performed to ensure compliance with the diet as outlined by dietician.
Control group
Active

Outcomes
Primary outcome [1] 293436 0
In obese (BMI >30kg/m2) non-diabetic women, does substantial pre-conception weight loss (10-15% body weight) result in a =/>10% reduction in maternal fasting plasma glucose (in mmol/L) at 26-28 weeks gestation when compared with maternal fasting plasma glucose (in mmol/L)from women who achieve modest pre-conception body weight (<3% body weight).
Timepoint [1] 293436 0
Fasting maternal glucose at 26-28 weeks gestation will be used as the primary outcome. Therefore, the primary outcome timepoint will be 26-28 weeks gestation.
Secondary outcome [1] 311040 0
In obese women (BMI >30kg/m2), does substantial pre-conception weight loss (10-15% body weight) when compared with modest pre-conception weight loss (<3% body weight) result in a reduction in the composite end-point of maternal gestational diabetes (IADPSG definition), large-for-gestational age, macrosomia, pre-eclampsia, intra-uterine growth restriction (IUGR), delivery prior to 37 weeks, caesarean section, shoulder dystocia/birth injury, neonatal hypoglycaemia, neonatal hyperbilirubinemia, neonatal intensive care or special care nursery admission.
Timepoint [1] 311040 0
End of pregnancy.
Secondary outcome [2] 311123 0
In obese women (BMI >30kg/m2), does substantial pre-conception weight loss (10-15% body weight) when compared with modest pre-conception weight loss (<3% body weight) reduce the time (in days) between the end of the weight maintenance phase and conception?
Timepoint [2] 311123 0
Date of conception (based on the earliest ultrasound or Last Menstrual Period if no ultrasound is available).
Secondary outcome [3] 311124 0
In obese women (BMI >30kg/m2), does substantial pre-conception weight loss (10-15% body weight), when compared with modest pre-conception weight loss (<3% body weight), result in a distinct pattern of DNA methylation in cells (cord blood and/or buccal mucosa) derived from the offspring?
Timepoint [3] 311124 0
End of pregnancy
Secondary outcome [4] 311126 0
4) Neonatal anthropometery

Length will be measured in centimetres using a measuring board.

Birth weight will be taken in grams within 72 hours of delivery using calibrated digital scales.

Head circumference will be measured using a tape measure. Measurements will be taken be the same examiner.

Skin fold thickness will be measured at each of three sites- left triceps, left sub scapular region and left flank. Each will be recorded in centimetres using Harpenden calipers. Measurements will be taken be the same examiner.

Timepoint [4] 311126 0
Within 72 hours of delivery
Secondary outcome [5] 311127 0
Maternal mean length of hospital stay
Timepoint [5] 311127 0
End of hospital stay based on hospital record.
Secondary outcome [6] 311128 0
Neonatal mean length of hospital stay
Timepoint [6] 311128 0
End of hospital stay based on hospital record.
Secondary outcome [7] 323036 0
In obese women (BMI >30kg/m2), does substantial pre-conception weight loss (10-15% body weight) when compared with modest pre-conception weight loss (<3% body weight) result in a reduction in rate of large-for-gestational age infants (birth weight >90th gentile for gestational age)?
Timepoint [7] 323036 0
End of pregnancy
Secondary outcome [8] 323037 0
In obese women (BMI >30kg/m2), does substantial pre-conception weight loss (10-15% body weight) when compared with modest pre-conception weight loss (<3% body weight) result in a reduction in the end-point of macrosomia (birth weight >4000g)?
Timepoint [8] 323037 0
End of pregnancy
Secondary outcome [9] 323038 0
In obese women (BMI >30kg/m2), does substantial pre-conception weight loss (10-15% body weight) when compared with modest pre-conception weight loss (<3% body weight) result in a reduction in the rate of gestational hypertension or pre-eclampsia (defined as persistent hypertension that develops in pregnancy with involvement of one or more maternal system)?
Timepoint [9] 323038 0
End of pregnancy
Secondary outcome [10] 323039 0
In obese women (BMI >30kg/m2), does substantial pre-conception weight loss (10-15% body weight) when compared with modest pre-conception weight loss (<3% body weight) result in a reduction in rate of intra-uterine growth restriction (IUGR) (defined as an estimated fetal weight <10th percentile for gestational age)?
Timepoint [10] 323039 0
End of pregnancy
Secondary outcome [11] 323040 0
In obese women (BMI >30kg/m2), does substantial pre-conception weight loss (10-15% body weight) when compared with modest pre-conception weight loss (<3% body weight) result in a reduction in the rate of neonates born prior to 37 completed weeks gestation?
Timepoint [11] 323040 0
End of pregnancy
Secondary outcome [12] 323041 0
In obese women (BMI >30kg/m2), does substantial pre-conception weight loss (10-15% body weight) when compared with modest pre-conception weight loss (<3% body weight) result in a reduction in the rate of primary caesarean section?
Timepoint [12] 323041 0
End of pregnancy
Secondary outcome [13] 323042 0
In obese women (BMI >30kg/m2), does substantial pre-conception weight loss (10-15% body weight) when compared with modest pre-conception weight loss (<3% body weight) result in a reduction in the shoulder dystocia/birth injury?
Timepoint [13] 323042 0
End of pregnancy
Secondary outcome [14] 323043 0
In obese women (BMI >30kg/m2), does substantial pre-conception weight loss (10-15% body weight) when compared with modest pre-conception weight loss (<3% body weight) result in a reduction in the rate of neonatal hypoglycaemia (neonatal blood glucose <2.6mmol/L within the neonatal period)?
Timepoint [14] 323043 0
End of pregnancy
Secondary outcome [15] 323044 0
In obese women (BMI >30kg/m2), does substantial pre-conception weight loss (10-15% body weight) when compared with modest pre-conception weight loss (<3% body weight) result in a reduction in the rate of clinically diagnosed neonatal hyperbilirubinemia?
Timepoint [15] 323044 0
End of pregnancy
Secondary outcome [16] 323045 0
In obese women (BMI >30kg/m2), does substantial pre-conception weight loss (10-15% body weight) when compared with modest pre-conception weight loss (<3% body weight) result in a reduction in rate of neonatal intensive care or special care nursery admission?
Timepoint [16] 323045 0
End of pregnancy
Secondary outcome [17] 323046 0
In obese women (BMI >30kg/m2), does substantial pre-conception weight loss (10-15% body weight) when compared with modest pre-conception weight loss (<3% body weight) result in a reduction in the rate of maternal gestational diabetes (IADPSG definition)?
Timepoint [17] 323046 0
End of pregnancy
Secondary outcome [18] 342222 0
In obese women (BMI >30kg/m2), does substantial pre-conception weight loss (10-15% body weight) when compared with modest pre-conception weight loss (<3% body weight) result in an increase live birth rate?
Timepoint [18] 342222 0
End of pregnancy
Secondary outcome [19] 342223 0
In obese women (BMI >30kg/m2), does substantial pre-conception weight loss (10-15% body weight) when compared with modest pre-conception weight loss (<3% body weight) result in no difference in gestational weight gain?
Timepoint [19] 342223 0
End of pregnancy

Eligibility
Key inclusion criteria
Planning pregnancy in the next 6 months
BMI equal or greater than 30 and equal or less than 55kg/m2
Living in Victoria Australia
Minimum age
18 Years
Maximum age
38 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Type 2 Diabetes
Type 1 Diabetes
Discretion of investigator
Physical or psychiatric illness that would preclude the use of Optifast
Currently pregnant or lactating
Currently undergoing reproductive technology treatment
Irreversible infertility
BMI <30kg/m2 or >55kg/m2
Age <18 years old or >38 years old
Not living in Victoria Australia
Not planning pregnancy in the next 6-12 months (regardless of the method of conception)

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Recruitment wil occur through:-
1. Social media (Facebook advertising linked to a website)
2. Radio and newspaper advertisement
3. Through University of Melbourne affiliated hospital clinics (Weight Control clinic at The Austin, Bariatric Clinic at RMH, Healthwise Clinic at RWH).

Once the patient has completed a 'Registration of Interest' form or has made contact with the trial site, the trial co-ordinator will phone screen the woman. They will then make an appointment at a mutually agreeable time.

They will then attend a full screening visit and if the patient is eligible and agreeable, the consent forms will be signed.

Patients will then be allocated to treatment groups as below.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Patients will be stratified based on age, BMI and parity. Computer generated random assignment of groups will occur within strata.

Allocation concealment occurs by central allocation of randomisation by computer.
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
As we hypothesised, individuals from our pilot study in group B had reduced glucose levels of approximately 10% (actual 9.12%, SE = 1.83, n = 24) compared to just 1.24% for those in Group A (SE = 1.40, n = 14). Of the 24 individuals who completed the weight loss phase, 10 have fallen pregnant and reached the 12 week gestation phase (Group A: n = 3; Group B = 7). Excitingly, the findings from the 7 women in Group B suggest that glucose reductions can be maintained at 12 weeks (mean 7.7% less glucose levels than at the beginning of the weight loss phase, SE = 1.74). On average, the change in glucose for these women between the end of the weight loss phase and 12 weeks gestation was a small reduction of 0.14 mmol/L. While we only have three women at 12 weeks gestation in group A, they too maintained similar glucose levels from the end of the weight loss phase (small average increase of 0.07mmol/L. The SD of percentage change at the end of the weight loss phase was 8.6 and then 9.9 for those measured at 26 weeks gestation. Allowing for at least a moderate effect size of 0.6 for difference in percentage decrease in glucose at 26 weeks gestation (i.e difference in means = 6, SD = 10; or slightly larger difference in means and larger SD) we require 45 women in each group to achieve 80% power. Allowing for 45% dropout (20% drop-out during the weight loss phase as indicated in our pilot data, plus an additional 25% drop-out to allow for women who fail to become pregnant or who experience a pregnancy loss <20 weeks gestation), we require approximately 164 individuals.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
5/11/2014
Actual
5/11/2014
Date of last participant enrolment
Anticipated
15/02/2018
Actual
10/02/2018
Date of last data collection
Anticipated
20/10/2019
Actual
Sample size
Target
164
Accrual to date
Final
164
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 3075 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [2] 3076 0
Mercy Hospital for Women - Heidelberg
Recruitment hospital [3] 3077 0
The Royal Women's Hospital - Parkville
Recruitment hospital [4] 3078 0
Austin Health - Austin Hospital - Heidelberg

Funding & Sponsors
Funding source category [1] 290138 0
University
Name [1] 290138 0
University of Melbourne
Country [1] 290138 0
Australia
Funding source category [2] 296035 0
Charities/Societies/Foundations
Name [2] 296035 0
Norman Beicher Medical Research Foundation Reserarch Funding
Country [2] 296035 0
Australia
Primary sponsor type
University
Name
University of Melbourne
Address
University of Melbourne
Grattan St
Parkville, VIC 3051
Country
Australia
Secondary sponsor category [1] 288848 0
Individual
Name [1] 288848 0
Professor Joe Proietto
Sir Edward Dunlop Chair of Medicine
Address [1] 288848 0
Centre for Metabolic Disease
Heidelberg Repatriation Hospital
Level 2 Boronia Building
Waterdale Rd
Heidelberg Heights VIC 3081
Country [1] 288848 0
Australia
Other collaborator category [1] 278221 0
Individual
Name [1] 278221 0
A/Professor Alison Nankervis
Address [1] 278221 0
Department of Diabetes and Endocrinology
Level 4
Royal Melbourne Hospital
Grattan St
Parkville VIC 3052
Country [1] 278221 0
Australia
Other collaborator category [2] 278222 0
Individual
Name [2] 278222 0
Professor Michael Permezel
Address [2] 278222 0
Department of Medicine, University of Melbourne
Level 4
Mercy Hospital for Women
Studley Rd
Heidelberg, VIC 3084
Country [2] 278222 0
Australia
Other collaborator category [3] 278953 0
University
Name [3] 278953 0
A/Professor Jeff Craig
Address [3] 278953 0
Epigenetics Department
Murdoch Childrens Research Institute
50 Flemington Rd,
Parkville, VIC 3052
Country [3] 278953 0
Australia
Other collaborator category [4] 278954 0
University
Name [4] 278954 0
Luke Prendergast
Address [4] 278954 0
Department of Mathematics
Latrobe University
Plenty Rd,
Bundoora, Victoria 3086
Country [4] 278954 0
Australia
Other collaborator category [5] 278955 0
University
Name [5] 278955 0
Priya Sumithran
Address [5] 278955 0
Department of Metabolic Medicine
University of Melbourne
Repatriation Hospital
Heidelberg Heights, Victoria 3081
Country [5] 278955 0
Australia
Other collaborator category [6] 278956 0
University
Name [6] 278956 0
Helen Skouteris
Address [6] 278956 0
Department of Psychology
Deakin University
221 Burwood Highway
Burwood, Victoria 3151
Country [6] 278956 0
Australia
Other collaborator category [7] 278957 0
Hospital
Name [7] 278957 0
Kate Stern
Address [7] 278957 0
Melbourne IVF
344 Victoria Parade
East Melbourne
Victoria, 3002
Country [7] 278957 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291844 0
Melbourne Health HREC
Ethics committee address [1] 291844 0
Ethics committee country [1] 291844 0
Australia
Date submitted for ethics approval [1] 291844 0
09/04/2014
Approval date [1] 291844 0
06/06/2014
Ethics approval number [1] 291844 0
HREC/14/MH/71
Ethics committee name [2] 291845 0
Austin Health HREC
Ethics committee address [2] 291845 0
Ethics committee country [2] 291845 0
Australia
Date submitted for ethics approval [2] 291845 0
04/06/2014
Approval date [2] 291845 0
23/07/2014
Ethics approval number [2] 291845 0
HREC/14/MH/71
Ethics committee name [3] 291846 0
Royal Women's Hospital
Ethics committee address [3] 291846 0
Ethics committee country [3] 291846 0
Australia
Date submitted for ethics approval [3] 291846 0
16/06/2014
Approval date [3] 291846 0
31/07/2014
Ethics approval number [3] 291846 0
HREC/14/MH/71
Ethics committee name [4] 291847 0
Mercy HREC
Ethics committee address [4] 291847 0
Ethics committee country [4] 291847 0
Date submitted for ethics approval [4] 291847 0
29/07/2014
Approval date [4] 291847 0
01/09/2014
Ethics approval number [4] 291847 0
R14/19, HREC/14/MH/71
Ethics committee name [5] 294867 0
Melbourne IVF
Ethics committee address [5] 294867 0
Ethics committee country [5] 294867 0
Australia
Date submitted for ethics approval [5] 294867 0
22/03/2015
Approval date [5] 294867 0
22/04/2015
Ethics approval number [5] 294867 0
Project 38/14 MIVF

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 215 215 0 0
/AnzctrAttachments/367299-Leaflet Version 2, August 2014.pdf

Contacts
Principal investigator
Name 52254 0
Prof Joseph Proietto
Address 52254 0
Centre for Metabolic Disease
Boronia Building
Repatriation Hospital
Austin Health
Waterdale Rd
Heidelberg Heights VIC 3081
Country 52254 0
Australia
Phone 52254 0
61 3 9496 2250
Fax 52254 0
61 3 9497 4554
Email 52254 0
j.proietto@unimelb.edu.au
Contact person for public queries
Name 52255 0
Sarah Price
Address 52255 0
Centre for Metabolic Disease
Boronia Building
Repatriation Hospital
Austin Health
Waterdale Rd
Heidelberg Heights, VIC 3081
Country 52255 0
Australia
Phone 52255 0
+ 61 3 9496 6221
Fax 52255 0
Email 52255 0
sarah.price@unimelb.edu.au
Contact person for scientific queries
Name 52256 0
Joseph Proietto
Address 52256 0
Centre for Metabolic Disease
Boronia Building
Repatriation Hospital
Austin Health
Waterdale Rd
Heidelberg Heights, VIC 3081
Country 52256 0
Australia
Phone 52256 0
61 3 9496 2250
Fax 52256 0
+61 3 9497 4554
Email 52256 0
j.proietto@unimelb.edu.au

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Plain language summaryNo Will enter when all publications submitted.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseTime to pregnancy after a prepregnancy very-low-energy diet program in women with obesity: substudy of a randomized controlled trial.2020https://dx.doi.org/10.1016/j.fertnstert.2020.06.033
N.B. These documents automatically identified may not have been verified by the study sponsor.