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Trial registered on ANZCTR


Registration number
ACTRN12615000400561
Ethics application status
Approved
Date submitted
10/04/2015
Date registered
29/04/2015
Date last updated
29/04/2015
Type of registration
Retrospectively registered

Titles & IDs
Public title
A four-armed randomised controlled demonstration trial of a multifaceted dietary intervention and probiotic capsules in obese pregnant women in the Counties Manukau Health region
Scientific title
A randomised controlled trial of nutritional interventions in obese pregnant women to optimise maternal pregnancy weight gain and infant birthweight: a demonstration study
Secondary ID [1] 286469 0
None
Universal Trial Number (UTN)
U1111-1155-0409
Trial acronym
HUMBA (Healthy mUMs and BAbies) Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pregnancy weight gain 294656 0
Infant birthweight 294657 0
Obesity 294784 0
Pregnancy 294785 0
Glucose metabolism 294786 0
Condition category
Condition code
Reproductive Health and Childbirth 294957 294957 0 0
Antenatal care
Diet and Nutrition 295126 295126 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a randomised controlled demonstration trial in 220 obese pregnant women to determine whether treatment with a probiotic capsule and/or dietary educational intervention:
1) Reduce excessive pregnancy weight gain
2) Reduce infant birthweight

Participants will be randomly allocated to one of the four study groups:
1) Probiotic and dietary intervention (group 1)
2) Placebo and dietary intervention (group 2)
3) Probiotic and routine dietary advice (group 3)
4) Placebo and routine dietary advice (group 4, controls).

Randomisation of participants to probiotics/placebo is double-blinded and the dietary intervention is unblinded.

Probiotics: The oral probiotic capsules will contain Lactobacillus rhamnosus GG and Bifidobacterium lactis BB12 (Chr. Hansen A/S, Horsholm, Denmark) at a dose of 7*10x9 colony-forming units per day each. The probiotics capsules are taken once-daily from recruitment (between 12 weeks and zero days and 17 weeks and 6 days) until delivery. Compliance with probiotic/placebo will be assessed by counting and documenting capsule numbers remaining in canisters when repeat supplies are provided to participants at monthly intervals.

Dietary intervention: Dietary education will be provided by a community health worker (CHW) trained in pregnancy nutrition, over four counselling sessions before the 26-28 week oral glucose tolerance test (OGTT). This will be complemented by 3-times weekly text messaging about healthy nutrition which will continue until birth. In-depth education will be provided by the CHW to women in the dietary intervention groups on healthy eating including: portion control, healthy food and drink choices, limiting energy dense foods, healthy recipes, label reading and managing cravings. Education on physical activity will cover four key physical activity messages (from the Te Wai o Rona program) which are relevant to pregnant women: look for ways to be active every day; increase daily exercise; move more, add more steps; and reduce sedentary leisure time. Each participant will have an initial 1 to 1.5 hour educational session (on average at about 14 weeks’ gestation) with the CHW. Three further 30 to 60 minute face-to-face sessions will occur with the CHW at two to three weekly intervals and be completed before the 26-28 week OGTT. Compliance with the dietary intervention will be assessed by the number of educational sessions participants attend with the CHW.
Intervention code [1] 291556 0
Prevention
Intervention code [2] 291557 0
Lifestyle
Comparator / control treatment
Control treatment for probiotics:
Identically-packaged placebo capsules comprise microcrystalline cellulose and dextrose anhydrate and are also supplied by Chr. Hansen A/S, Horsholm, Denmark. Placebo capsules are also taken once-daily.

Control for dietary intervention: Participants in the routine dietary advice groups will receive two NZ Ministry of Health pamphlets which are available in routine antenatal care: 1) "Guidance for Healthy Weight Gain in Pregnancy" and 2) "Eating for Healthy Pregnant Women" .
The "Guidance for Healthy Weight Gain in Pregnancy" contains information about recommended optimum healthy weight gain by maternal body mass index categories (according to 2009 Institute of Medicine Guidelines), risks of excess weight gain and some simple tips about nutrition and physical activity that may assist with optimising weight gain.
"Eating for Healthy Pregnant Women" is developed from the New Zealand "Food and Nutrition Guidelines for Healthy Pregnant and Breastfeeding Women".
This leaflet incorporates information on: food for a healthy mother and baby, dietary variety, drinking plenty of fluids, foods low in fat, salt and sugar, keeping active, food safety and listeria, salmonella, campylobacter and toxoplasma, snack and lunch ideas, eating well during pregnancy, indigestion, heartburn, constipation, alcohol, being smokefree, folic acid, iodine, and vitamin D.
Control group
Placebo

Outcomes
Primary outcome [1] 294713 0
Proportion of participants with excessive pregnancy weight gain by 2009 Institute of Medicine Criteria measured on Seca 876 scales.
Timepoint [1] 294713 0
Weight gain is measured between study recruitment and the research visit at 36 weeks of gestation.
Primary outcome [2] 294714 0
Infant birthweight (in the delivery unit after birth) measured using Seca 334 scales to the nearest gram
Timepoint [2] 294714 0
At birth
Secondary outcome [1] 314002 0
Fasting, 1 hour and 2 hour maternal glucose levels


Timepoint [1] 314002 0
26-28 weeks gestation extended oral glucose tolerance test
Secondary outcome [2] 314003 0
Diet quality and healthy eating index as assessed by the NZ Food Frequency Questionnaire - Short Form
Ref: Sam et al. Public Health Nutrition 2014:17(2):287-96
Timepoint [2] 314003 0
Between recruitment and research visit at 26-28 weeks' of gestation, and recruitment and follow up research visit at 4-6 months postpartum.
Secondary outcome [3] 314004 0
Gestational Diabetes by IADPSG criteria
Ref: Diabetes Care. 2010 Mar;33(3):676-82.
Timepoint [3] 314004 0
All women will have an extended glucose tolerance test at 26-28 weeks' of gestation.
Secondary outcome [4] 314005 0
Pregnancy Induced Hypertension
Ref: Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health. 2014;4(2):97-104.
Timepoint [4] 314005 0
Pregnancy induced hypertension developing after 20 weeks gestation
Secondary outcome [5] 314006 0
Maternal weight measured on Seca 876 scales in kilograms and grams and infant weight measured using Seca 334 scales in kilograms and grams
Timepoint [5] 314006 0
at follow up visit at 4-6 months postpartum
Secondary outcome [6] 314007 0
HBA1c measured using the Roche Cobas b101 point of care finger prick blood test.
Timepoint [6] 314007 0
Research visits at 28, 36 weeks of gestation and 4-6 months postpartum

Eligibility
Key inclusion criteria
1) Women with a BMI greater than or equal to 30 kg/m2,
2) singleton pregnancy
3) between 12 weeks 0 days and 17 weeks and 6 days of gestation
4) able to provide informed written consent
Minimum age
No limit
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1) pre-existing diabetes or HbA1c at booking >=50 mmol/mol
2) taking probiotic supplements
3) known congenital abnormality
4) medications or medical conditions which alter glucose metabolism
5) bariatric surgery
6) severe hyperemesis

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)
We will have a multi-pronged approach to optimise enrolment including through lead maternity caregivers (self-employed midwives), community antenatal clinics, general practitioners, practice nurses, ultrasound clinics and community contacts. Lead maternity caregivers will notify the research team about eligible women who are interested in participating and the research assistant will contact the woman and arrange a time to meet her to explain the study, confirm eligibility and obtain informed consent.

In order to exclude women with previously unrecognised Type 2 diabetes, HbA1c will be measured (using the Roche cobas b 101 point-of-care system) in all participants prior to randomisation. If HbA1c is greater or equal to 50, women will be considered to have undiagnosed diabetes, be deemed ineligible and referred to the Diabetes in Pregnancy Service at Counties Manukau Health.

Christian Hansen have provided identically packaged placebo and probiotic capsules in canisters (containing 31 capsules each). AnQual Laboratories (School of Pharmacy, University of Auckland) has labelled the canisters containing probiotic/placebo capsules using a pre-allocated random list. The kit list used to label the pills was generated by the Project Manager (the only HUMBA staff member unblinded to probiotic/placebo allocation) and AnQual. The Excel random function was used to generate a random sequence of numbers to label each probiotic/placebo alutube. This list has secure password protection and is currently stored with AnQual.

Randomisation will be undertaken using a web-based protocol, randomize.net (http://randomize.net). For randomisation purposes, each research midwife will serve as a proxy for ‘clinical site’ (this will enable each research midwife to be able to dispense the randomised study capsules at the end of the recruitment interview). Participants will be stratified by ‘clinical site’ (n=2) and BMI category (BMI of 30-34.9 or BMI >=35 kg/m2) and randomly allocated to one of the four study groups.

The canisters (half probiotics and half placebo) will be sent once-monthly to the study location. All clinical and research staff and participants will be masked to the randomised probiotic/placebo allocation.

Compliance with probiotics/placebo will be assessed by the research team via patient self-report and counting and documenting capsules remaining in canisters when repeat supplies are provided.

Although it will not be possible for clinical and research staff to be blinded to the dietary intervention allocation, the key health outcomes including pregnancy weight gain and infant birthweight are not subject to bias.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be undertaken using random block sizes generated by the study statistician.

Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Factorial
Other design features
4 arm randomised controlled demonstration trial
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Sample size calculation and power:
A total of 220 participants will be recruited. With 80% power and 100 subjects remaining in each main intervention group (allowing 10% lost to follow-up) we can detect:
1) 25% reduction in excessive pregnancy weight gain from 80% to 60% (based on an 80% rate of excess weight gain in obese participants in the SCOPE study), and
2) 227 g difference in mean birthweight (based on Counties Manukau Health data; mean 3,638, SD 521).

To allow for the two primary outcomes an alpha of 0.025 is used for the power calculations (Bonferroni approach).

Statistical Analyses:
Binary endpoints will be analysed using logistic regression to estimate odds ratios of treatment groups compared to the control group.

Continuous outcomes will be modelled using generalised linear models to estimate any changes in outcomes with the treatment group compared to the control group.

Multivariable analyses will control for potential confounders including BMI and ethnicity. Outcomes compared across all groups will be adjusted for multiple comparisons.

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 outside Australia
Country [1] 6801 0
New Zealand
State/province [1] 6801 0
Auckland

Funding & Sponsors
Funding source category [1] 291073 0
University
Name [1] 291073 0
University of Auckland
Address [1] 291073 0
Pvt Bag 92019, Auckland Mail Centre, Auckland 1142
Country [1] 291073 0
New Zealand
Funding source category [2] 291074 0
Charities/Societies/Foundations
Name [2] 291074 0
CureKids
Address [2] 291074 0
58 Surrey Cres
Grey Lynn
Auckland 1142
Country [2] 291074 0
New Zealand
Funding source category [3] 291075 0
Hospital
Name [3] 291075 0
Counties Manukau Health
Address [3] 291075 0
19 Lambie Drive
Manukau 2104
Auckland
Country [3] 291075 0
New Zealand
Primary sponsor type
University
Name
University of Auckland
Address
Pvt Bag 92019, Auckland Mail Centre, Auckland 1142
Country
New Zealand
Secondary sponsor category [1] 289753 0
Hospital
Name [1] 289753 0
Counties Manukau Health
Address [1] 289753 0
19 Lambie Drive
Manukau 2104
Auckland
Country [1] 289753 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292658 0
Health & Disability Ethics Committee
Ethics committee address [1] 292658 0
C/ MEDSAFE,
PO Box 5013,
Wellington 6011
Ethics committee country [1] 292658 0
New Zealand
Date submitted for ethics approval [1] 292658 0
Approval date [1] 292658 0
22/12/2014
Ethics approval number [1] 292658 0
14/STH/205

Summary
Brief summary
One third of New Zealand children are overweight or obese, with much higher rates among Pacific and Maori children (51% and 43%, respectively) who form about half the population in Counties Manukau district, South Auckland (our research area). In pregnant obese women (40% in Counties Manukau), unborn babies are exposed to excess nutrients inside the womb, making them more likely to be born large and become obese as children and adults. When obese women gain excessive weight during pregnancy (the majority) or develop gestational diabetes mellitus, problems for the baby are compounded.

An important first step to breaking this vicious intergenerational cycle is to develop successful interventions for obese women starting in early pregnancy. If excessive pregnancy weight gain can be limited maternal and infant health may be improved. The proposed demonstration project will recruit obese women in early pregnancy and will test two novel, practical interventions: (1) a culturally appropriate, affordable, sustainable dietary education intervention; and (2) probiotic/placebo capsules. This demonstration project is an important first step to gaining insight into dietary interventions that may work in the South Auckland population, which has one of the highest rates of obesity in the world.
Trial website
In development- not yet live.
www.humba.auckland.ac.nz
Trial related presentations / publications
Nil at present time
Public notes
Nil at present time

Contacts
Principal investigator
Name 56266 0
Prof Lesley ME McCowan
Address 56266 0
Department of Obstetrics and Gynaecology
Faculty of Medical and Health Science,
University of Auckland
Private Bag 92019
Auckland 1010
Country 56266 0
New Zealand
Phone 56266 0
+64-21-243-8402
Fax 56266 0
+64-9-303-5969
Email 56266 0
l.mccowan@auckland.ac.nz
Contact person for public queries
Name 56267 0
Prof Lesley ME McCowan
Address 56267 0
Department of Obstetrics and Gynaecology
Faculty of Medical and Health Science,
University of Auckland
Private Bag 92019
Auckland 1010
Country 56267 0
New Zealand
Phone 56267 0
+64-21-243-8402
Fax 56267 0
+64-9-303-5969
Email 56267 0
l.mccowan@auckland.ac.nz
Contact person for scientific queries
Name 56268 0
Prof Lesley ME McCowan
Address 56268 0
Department of Obstetrics and Gynaecology
Faculty of Medical and Health Science,
University of Auckland
Private Bag 92019
Auckland 1010
Country 56268 0
New Zealand
Phone 56268 0
+64-21-243-8402
Fax 56268 0
+64-9-303-5969
Email 56268 0
l.mccowan@auckland.ac.nz

No information has been provided regarding IPD availability
Summary results
No Results