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Trial registered on ANZCTR


Registration number
ACTRN12620000359932p
Ethics application status
Not yet submitted
Date submitted
28/01/2020
Date registered
13/03/2020
Date last updated
13/03/2020
Date data sharing statement initially provided
13/03/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Probiotics in the prevention of Gestational Diabetes Mellitus in women at increased risk: a prospective randomised controlled trial.
Scientific title
Probiotics in the prevention of Gestational Diabetes Mellitus in women at increased risk: a prospective randomised controlled trial.
Secondary ID [1] 300355 0
Nil known
Universal Trial Number (UTN)
U1111-1247-2365
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gestational Diabetes Mellitus 315968 0
Condition category
Condition code
Reproductive Health and Childbirth 314244 314244 0 0
Fetal medicine and complications of pregnancy
Metabolic and Endocrine 314504 314504 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Women will be recruited to the study at their booking-in appointment with the antenatal clinic (usually at 12 week's pregnancy). Participating women will be randomised to the intervention or control group. The intervention group will be given probiotic capsules to be taken once daily from enrolment until the results are received from their Glucose Tolerance Test, which is conducted at their 26-28 week antenatal care visit. The probiotic will contain a combination of strains lactobacillus rhamnosus and Bifidobacterium animalis ssp lactis and/or Bifidobacterium breve and Bifidobacterium longum as these are previously well researched strains specific for pregnancy. Lactobacillus rhamnosus and Bifidovacterium animalis ssp lactis have been shown to influence glucose metabolism through their immunoregulatory properties. The probiotic and placebo will be manufactured and supplied by Metagenetics (Aust) Pty Ltd. Given the fragile nature of the microbes in probiotics, women will be instructed to keep the capsules in a refrigerator and to avoid taking them within 10 minutes of consuming hot food or fluid. Adherence to the intervention will be monitored by counting the number of capsules in bottles returned by participants at their 26-28 week antenatal clinic visit. As per standard care, at their 26-28 antenatal clinic, all women will complete an Oral Glucose Tolerance Test. Completion of the test marks the end of their participation in the study.
Intervention code [1] 316633 0
Prevention
Comparator / control treatment
The control group will be given placebo capsules containing (maize-derived maltodextrin) to be taken once daily from enrolment until the results are received from their Glucose Tolerance Test, which is conducted at their 26-28 week antenatal care visit.. The placebo will be identical in appearance and smell to the probiotic. The control group will also be instructed to keep the capsules in a refrigerator and to avoid taking them within 10 minutes of consuming hot food or fluid.
Control group
Placebo

Outcomes
Primary outcome [1] 322630 0
The primary outcome is the incidence of gestational diabetes in the intervention group and the control group. This outcome will be assessed by the Oral Glucose Tolerance Test which is a routine test for pregnant women attending their 26-28 week antenatal care visit.
Timepoint [1] 322630 0
Antenatal care appointment at week 26-28 of pregnancy.
Secondary outcome [1] 379107 0
Change in weight from booking-in appointment with the antenatal clinic (approximately 12 weeks pregnancy) to routine antenatal care appointment at week 26-28 of pregnancy. Weight will be measured by antenatal clinic staff using clinic weighing scales.
Timepoint [1] 379107 0
Week 26-28 of pregnancy.

Eligibility
Key inclusion criteria
All pregnant women >10 weeks gestation, in a singleton pregnancy at increased risk of gestational diabetes as per the Australasian Diabetes in Pregnancy Society (ADIPS) criteria will be eligible for the study:
• Previous GDM
• Maternal age 18 years to 40 years
• Family history of diabetes (1st degree relative with diabetes or a sister with GDM)
• BMI over 35kg/m2
• Previous macrosomia (baby birth weight over 4500g or over 90th centile)
• Polycystic ovarian syndrome
Minimum age
18 Years
Maximum age
40 Years
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
• Not being able to read and understand English – unable to provide informed consent.
• Age <18 years
• Pregnancy >16 weeks gestation at recruitment
• Known pre-existing diabetes, impaired fasting glucose or impaired glucose tolerance
• GDM prior to recruitment as diagnosed by early pregnancy glucose testing – Early
pregnancy glucose testing routinely done for women at increased risk of GDM
• Medications likely to influence glucose metabolism – metformin, glucocorticoids,
immunosuppressants
• Medical conditions with altered glucose metabolism – Cushing/s syndrome, hepatic
cirrhosis
• Known major fetal anomaly on ultrasound
• Known current ingestion of probiotics via capsules or sachets
• Antibiotic use during the study period

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)
The allocation of participants to either the intervention group or the control group will be concealed to the persons recruiting participants. Computer-based randomisation will be centrally conducted with a study group (A or B) marked on the enrolment form. Only after participants have signed the study consent form, will an enrolment form be selected from a file containing all enrolment forms. Study recruiters will be instructed to remove the first enrolment form only. The unique study ID and study group on the form will match a bottle with the same ID of either the treatment or placebo. Study recruiters will not be aware which group (A or B) contains the probiotics.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A random group allocation table will be centrally generated using Stata 15 software.
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
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The study will investigate both odds ratios and relative risks of GDM in the control and intervention groups. Unadjusted odds ratios and relative risks will be calculated. Bivariate analyses will investigate associations between baseline variables (e.g. demographic characteristics, maternal history, obstetric history and other risk factors parity) and development of GDM. A multivariable logistic regression model will be used to estimate the odds of women developing GDM in the intervention group vs. control group. An intention to treat analysis will be done with the primary analysis to account for poor compliance with trial participation.

Recruitment
Recruitment status
Not yet 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)
TAS
Recruitment hospital [1] 15679 0
North West Regional Hospital - Burnie
Recruitment hospital [2] 15680 0
Mersey Community Hospital - Latrobe
Recruitment postcode(s) [1] 29098 0
7320 - Burnie
Recruitment postcode(s) [2] 29099 0
7307 - Latrobe

Funding & Sponsors
Funding source category [1] 304945 0
Hospital
Name [1] 304945 0
North West Regional Hospital
Address [1] 304945 0
North West Regional Hospital
Hospitals' Campus, Brickport Road
Burnie
Tasmania 7320
Country [1] 304945 0
Australia
Primary sponsor type
Individual
Name
Dr Anushika Samarage
Address
North West Regional Hospital
Hospitals' Campus, Brickport Road
Burnie
Tasmania 7320
Country
Australia
Secondary sponsor category [1] 305298 0
None
Name [1] 305298 0
Address [1] 305298 0
Country [1] 305298 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 305194 0
University of Tasmania Tasmania Health & Medical Human Research Ethics Committee
Ethics committee address [1] 305194 0
Health and Medical Research Ethics Committee
Office of Research Services
Private Bag 1
Hobart TAS 7001
Ethics committee country [1] 305194 0
Australia
Date submitted for ethics approval [1] 305194 0
27/03/2020
Approval date [1] 305194 0
Ethics approval number [1] 305194 0

Summary
Brief summary
The purpose of the study is to establish if probiotics taken in pregnancy can reduce the incidence of gestational diabetes (GDM) in women who are at increased risk of GDM. The study hypothesis is the administration of probiotics to pregnant women at risk of gestational diabetes from 12 weeks of gestation reduces the incidence of GDM diagnosed at 26-28 weeks gestation. The study is a prospective, double-blinded randomized controlled trial. Women attending public hospital antenatal services who are at increased risk of developing GDM will be invited to participate. Participants will be randomly allocated to either the control group receiving a placebo or the intervention group receiving probiotics daily from booking in appointment (usually approx. 12 weeks gestation) until the Oral Glucose Tolerance Test (routinely done at 26-28 weeks gestation). Women. The primary outcome is incidence of GDM in the control and intervention groups..
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 99562 0
Dr Anushika Samarage
Address 99562 0
North West Regional Hospital
Hospitals' Campus, Brickport Road
Burnie
Tasmania
7320
Country 99562 0
Australia
Phone 99562 0
+61 0477427426
Fax 99562 0
Email 99562 0
anushika.samarage@ths.tas.gov.au
Contact person for public queries
Name 99563 0
Dr Anushika Samarage
Address 99563 0
North West Regional Hospital
Hospitals' Campus, Brickport Road
Burnie
Tasmania
7320
Country 99563 0
Australia
Phone 99563 0
+61 0477427426
Fax 99563 0
Email 99563 0
anushika.samarage@ths.tas.gov.au
Contact person for scientific queries
Name 99564 0
Dr Anushika Samarage
Address 99564 0
North West Regional Hospital
Hospitals' Campus, Brickport Road
Burnie
Tasmania
7320
Country 99564 0
Australia
Phone 99564 0
+61 0477427426
Fax 99564 0
Email 99564 0
anushika.samarage@ths.tas.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
We currently have no plans to make individual participant data available, however if we receive a request we will seek ethics committee approval prior to sharing data. We would be willing to share de-identified individual participant data underlying published results.
When will data be available (start and end dates)?
Immediately following publication and for 3 years following main results publication.
Available to whom?
The data would be provided on a case-by-case basis at the discretion of the Principal Investigator.
Available for what types of analyses?
The data would be provided only to achieve the aims in the approved proposal.
How or where can data be obtained?
Access subject to approvals by Principal Investigator: Dr Anushika Samarage, anushika.samarage@ths.tas.gov.au
What supporting documents are/will be available?
Study protocol
Informed consent form
Ethical approval
How or where can supporting documents be obtained?
Type [1] 6589 0
Study protocol
Citation [1] 6589 0
Link [1] 6589 0
Email [1] 6589 0
anushika.samarage@ths.tas.gov.au
Other [1] 6589 0
Attachment [1] 6589 0
Type [2] 6590 0
Informed consent form
Citation [2] 6590 0
Link [2] 6590 0
Email [2] 6590 0
anushika.samarage@ths.tas.gov.au
Other [2] 6590 0
Attachment [2] 6590 0
Type [3] 6591 0
Ethical approval
Citation [3] 6591 0
Link [3] 6591 0
Email [3] 6591 0
anushika.samarage@ths.tas.gov.au
Other [3] 6591 0
Attachment [3] 6591 0
Summary results
No Results