ANZCTR - Registration

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]

Nil known

Universal Trial Number (UTN)

Trial acronym

POP Study

Linked study record

Health condition

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

Obesity

Pre-pregnancy weight loss

Condition category

Condition code

Diet and Nutrition

Obesity

Reproductive Health and Childbirth

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]

Prevention

Intervention code [2]

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]

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]

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]

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]

End of pregnancy.

Secondary outcome [2]

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]

Date of conception (based on the earliest ultrasound or Last Menstrual Period if no ultrasound is available).

Secondary outcome [3]

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]

End of pregnancy

Secondary outcome [4]

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]

Within 72 hours of delivery

Secondary outcome [5]

Maternal mean length of hospital stay

Timepoint [5]

End of hospital stay based on hospital record.

Secondary outcome [6]

Neonatal mean length of hospital stay

Timepoint [6]

End of hospital stay based on hospital record.

Secondary outcome [7]

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]

End of pregnancy

Secondary outcome [8]

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]

End of pregnancy

Secondary outcome [9]

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]

End of pregnancy

Secondary outcome [10]

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]

End of pregnancy

Secondary outcome [11]

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]

End of pregnancy

Secondary outcome [12]

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]

End of pregnancy

Secondary outcome [13]

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]

End of pregnancy

Secondary outcome [14]

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]

End of pregnancy

Secondary outcome [15]

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]

End of pregnancy

Secondary outcome [16]

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]

End of pregnancy

Secondary outcome [17]

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]

End of pregnancy

Secondary outcome [18]

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]

End of pregnancy

Secondary outcome [19]

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]

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

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]

Royal Melbourne Hospital - City campus - Parkville

Recruitment hospital [2]

Mercy Hospital for Women - Heidelberg

Recruitment hospital [3]

The Royal Women's Hospital - Parkville

Recruitment hospital [4]

Austin Health - Austin Hospital - Heidelberg

Funding & Sponsors

Funding source category [1]

University

Name [1]

University of Melbourne

Country [1]

Australia

Funding source category [2]

Charities/Societies/Foundations

Name [2]

Norman Beicher Medical Research Foundation Reserarch Funding

Country [2]

Australia

Primary sponsor type

University

Name

University of Melbourne

Country

Australia

Secondary sponsor category [1]

Individual

Name [1]

Professor Joe Proietto
Sir Edward Dunlop Chair of Medicine

Country [1]

Australia

Other collaborator category [1]

Individual

Name [1]

A/Professor Alison Nankervis

Country [1]

Australia

Other collaborator category [2]

Individual

Name [2]

Professor Michael Permezel

Country [2]

Australia

Other collaborator category [3]

University

Name [3]

A/Professor Jeff Craig

Country [3]

Australia

Other collaborator category [4]

University

Name [4]

Luke Prendergast

Country [4]

Australia

Other collaborator category [5]

University

Name [5]

Priya Sumithran

Country [5]

Australia

Other collaborator category [6]

University

Name [6]

Helen Skouteris

Country [6]

Australia

Other collaborator category [7]

Hospital

Name [7]

Kate Stern

Country [7]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Melbourne Health HREC

Ethics committee address [1]

Office for Research
Royal Melbourne Hospital
Grattan St
Parkville, VIC 3052

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

09/04/2014

Approval date [1]

06/06/2014

Ethics approval number [1]

HREC/14/MH/71

Ethics committee name [2]

Austin Health HREC

Ethics committee address [2]

Office for Research
Austin Health
Studley Rd
Heidelberg, VIC 3084

Ethics committee country [2]

Australia

Date submitted for ethics approval [2]

04/06/2014

Approval date [2]

23/07/2014

Ethics approval number [2]

HREC/14/MH/71

Ethics committee name [3]

Royal Women's Hospital

Ethics committee address [3]

Research and Ethics
Crn Grattan St and Flemington Rd
Parkville, VIC 3052

Ethics committee country [3]

Australia

Date submitted for ethics approval [3]

16/06/2014

Approval date [3]

31/07/2014

Ethics approval number [3]

HREC/14/MH/71

Ethics committee name [4]

Mercy HREC

Ethics committee address [4]

Mercy Health HREC
Level 6
Mercy Hospital for Women
Studley Rd
Heidelberg VIC 3084

Ethics committee country [4]

Date submitted for ethics approval [4]

29/07/2014

Approval date [4]

01/09/2014

Ethics approval number [4]

R14/19, HREC/14/MH/71

Ethics committee name [5]

Melbourne IVF

Ethics committee address [5]

Melbourne IVF
344 Victoria Parade
East Melbourne, 
Victoria, 3002

Ethics committee country [5]

Australia

Date submitted for ethics approval [5]

22/03/2015

Approval date [5]

22/04/2015

Ethics approval number [5]

Project 38/14 MIVF

Summary

Brief summary

This is a two arm parallel group randomised controlled trial to determine if substantial weight loss is superior to modest weight loss in reducing maternal glucose at 26-28 weeks gestation and therefore preventing adverse maternal and neonatal pregnancy outcomes.

Trial website

www.popstudy.com.au

Public notes

Attachments [1]

/AnzctrAttachments/367299-Leaflet Version 2, August 2014.pdf

Contacts

Principal investigator

Name

Prof Joseph Proietto

Address

Centre for Metabolic Disease
Boronia Building
Repatriation Hospital
Austin Health
Waterdale Rd
Heidelberg Heights VIC 3081

Country

Australia

Phone

61 3 9496 2250

Email

[email protected]

Contact person for public queries

Name

Sarah Price

Address

Centre for Metabolic Disease
Boronia Building
Repatriation Hospital
Austin Health
Waterdale Rd
Heidelberg Heights, VIC 3081

Country

Australia

Phone

+ 61 3 9496 6221

Email

[email protected]

Contact person for scientific queries

Name

Joseph Proietto

Address

Centre for Metabolic Disease
Boronia Building
Repatriation Hospital
Austin Health
Waterdale Rd
Heidelberg Heights, VIC 3081

Country

Australia

Phone

61 3 9496 2250

Email

[email protected]

Trial Review

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