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Trial registered on ANZCTR


Registration number
ACTRN12618000450213
Ethics application status
Approved
Date submitted
2/03/2018
Date registered
28/03/2018
Date last updated
28/03/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
An intergenerational prebiotic approach to establishment of a healthy colonic microbiome in infants.
Scientific title
An intergenerational prebiotic approach to establishment of a healthy colonic microbiome in infants
Secondary ID [1] 294218 0
Nil known
Universal Trial Number (UTN)
U1111-1210-1784
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Environmental Enteric Dysfunction 306879 0
Gut dysbiosis 306880 0
Stunting 306881 0
Condition category
Condition code
Oral and Gastrointestinal 305976 305976 0 0
Normal oral and gastrointestinal development and function
Diet and Nutrition 305977 305977 0 0
Other diet and nutrition disorders
Oral and Gastrointestinal 306144 306144 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Resistant starch as High Amylose Maize Starch (HAMS) was fed to two groups of participants for 6 weeks as follows:
Women of child-bearing age
Milkshakes containing 25 grams of HAMS were chosen as the most appropriate food ‘vehicle.’ The 25 gram dosage was based on the literature (Hu et al. 2016; Le Leu et al. 2009; Muir et al. 1998). HAMS was purchased from Ingredion Australia (http://apac.ingredion.com/) and shipped to India where it was then measured into 25 gram portions prior to the study for ease of preparation by staff. Milkshakes were prepared and delivered to participants by study staff on a daily basis. Bottles were labelled with the participant ID. Participants were asked to consume the milkshake in its entirety each day for the 42 days of the study and did so under the observation of study staff. Stool samples were collected at baseline and thereafter at 2 weekly intervals until 2 weeks post-intervention.

Early-weaning infants
The food vehicle options comprised those foods that participants were eating in their usual diet. 10 grams of HAMS was added to the preferred daily food of each participant at the point of consumption. Stool samples were collected at baseline and thereafter at 2 weekly intervals until 2 weeks post-intervention.
Intervention code [1] 300511 0
Prevention
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 305012 0
pH of stool samples-Supernatant pH was determined before and after fermentation of stool samples using a Mettler Toledo pH meter (Mettler-Toledo Ltd., Columbus OH, USA).
Timepoint [1] 305012 0
Assessment of this outcome occurred at day 0 before the feeding intervention started (sample 1) and then at 2 weekly intervals until the end of the feeding intervention period which extended for 6 weeks in total (samples 2, 3 and 4). Day 0 measurements (sample 1) were compared to day 42 measurements (sample 4-end of feeding period) to test the relevant study hypothesis. The final measurement (sample 5) was taken at 2 weeks post-intervention to determine if changes were sustained after the feeding intervention ceased.
Secondary outcome [1] 343870 0
Acetate concentrations of stool samples measured using GC-FID (Gas Chromatography with Flame Ionization Detector.)
Timepoint [1] 343870 0
Assessment of this outcome occurred at day 0 before the feeding intervention started (sample 1) and then at 2 weekly intervals until the end of the feeding intervention period which extended for 6 weeks in total (samples 2, 3 and 4). Day 0 measurements (sample 1) were compared to day 42 measurements (sample 4-end of feeding period) to test the relevant study hypothesis. The final measurement (sample 5) was taken at 2 weeks post-intervention to determine if changes were sustained after the feeding intervention ceased.
Secondary outcome [2] 344364 0
Butyrate concentrations of stool samples measured using GC-FID (Gas Chromatography with Flame Ionization Detector.)
Timepoint [2] 344364 0
Assessment of this outcome occurred at day 0 before the feeding intervention started (sample 1) and then at 2 weekly intervals until the end of the feeding intervention period which extended for 6 weeks in total (samples 2, 3 and 4). Day 0 measurements (sample 1) were compared to day 42 measurements (sample 4-end of feeding period) to test the relevant study hypothesis. The final measurement (sample 5) was taken at 2 weeks post-intervention to determine if changes were sustained after the feeding intervention ceased.
Secondary outcome [3] 344365 0
Propionate concentrations of stool samples measured using GC-FID (Gas Chromatography with Flame Ionization Detector.)
Timepoint [3] 344365 0
Assessment of this outcome occurred at day 0 before the feeding intervention started (sample 1) and then at 2 weekly intervals until the end of the feeding intervention period which extended for 6 weeks in total (samples 2, 3 and 4). Day 0 measurements (sample 1) were compared to day 42 measurements (sample 4-end of feeding period) to test the relevant study hypothesis. The final measurement (sample 5) was taken at 2 weeks post-intervention to determine if changes were sustained after the feeding intervention ceased.
Secondary outcome [4] 344366 0
Composite method-16S rRNA gene sequencing to determine type and number of bacterial species in stool samples. Weighted Unifrac method will be used to measure both abundance and presence/absence of bacterial species in stool.
Timepoint [4] 344366 0
Assessment of this outcome occurred at day 0 before the feeding intervention started (sample 1) and then at 2 weekly intervals until the end of the feeding intervention period which extended for 6 weeks in total (samples 2, 3 and 4). Day 0 measurements (sample 1) were compared to day 42 measurements (sample 4-end of feeding period) to test the relevant study hypothesis. The final measurement (sample 5) was taken at 2 weeks post-intervention to determine if changes were sustained after the feeding intervention ceased.

Eligibility
Key inclusion criteria
Women: aged 18 to 25 years (inclusive)
Infants: aged 6-7 months of age (inclusive)
Minimum age
6 Months
Maximum age
25 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Women:
• Presence of any chronic disease
• Currently pregnant or intending to have a child in the next two months

Infants:
• Presence of any chronic disease

Study design
Purpose of the study
Prevention
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Previous studies have indicated that fecal pH in healthy Indian children is 6.2 (SD 0.4). Using this standard deviation, and assuming that there is a true difference of 0.4 between baseline and the feeding intervention, a sample size was calculated for an alpha error of 5% and study power of 80%.
Within each sub-group (women and infants), differences between pH, SCFA concentrations and bacterial counts at 0 and 42 days will be tested for significance using paired t-tests assuming equal variances and considering both sides of the distribution (two-tailed distribution). Differences will be considered significant if p=0·05.

Recruitment
Recruitment status
Completed
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] 9642 0
India
State/province [1] 9642 0
Tamil Nadu and Odisha states.

Funding & Sponsors
Funding source category [1] 298853 0
Charities/Societies/Foundations
Name [1] 298853 0
Bill & Melinda Gates Foundation
Address [1] 298853 0
440 Fifth Avenue North Seattle WA 98109
Country [1] 298853 0
United States of America
Funding source category [2] 298855 0
Government body
Name [2] 298855 0
Biotechnology Industry Research Assistance Council (BIRAC)
Address [2] 298855 0
1st Floor ,MTNL Building ,9 , CGO Complex, Lodhi Road, New Delhi-110003
Country [2] 298855 0
India
Primary sponsor type
University
Name
SRM Institutes for Medical Science
Address
No.1, Jawaharlal Nehru Salai, 100 Feet Road, Near Vadapalani Metro Station, Chennai, Tamil Nadu 600026
Country
India
Secondary sponsor category [1] 298057 0
University
Name [1] 298057 0
Flinders University
Address [1] 298057 0
Flinders Drive
Bedford Park
SA 5042
Country [1] 298057 0
Australia
Secondary sponsor category [2] 298060 0
Other Collaborative groups
Name [2] 298060 0
South Australian Health and Medical Research Institute (SAHMRI)
Address [2] 298060 0
Infection and Immunity Theme
North Terrace
Adelaide
South Australia 5000
Country [2] 298060 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299801 0
Southern Adelaide Clinical Human Research Ethics Committee
Ethics committee address [1] 299801 0
Office for Research
Corporate Services
Southern Adelaide Local Health Network
Ward 6C, Room 219, Flinders Medical Centre
Bedford Park 5042
Ethics committee country [1] 299801 0
Australia
Date submitted for ethics approval [1] 299801 0
19/07/2016
Approval date [1] 299801 0
17/11/2016
Ethics approval number [1] 299801 0
317.16

Summary
Brief summary
Resistant starch is the amount of total starch consumed which escapes digestion in the small intestine, reaching the large intestine where it becomes a substrate for resident microbes, producing short chain fatty acids (SCFA). This increase in SCFA results in an environment in which beneficial microbes prosper, ultimately leading to a healthier microbiome in the large intestine and therefore acting as a ‘prebiotic’. Our hypothesis is that feeding this prebiotic starch (in the form of high amylose maize starch or’ HAMS’) to young women of reproductive age and to infants will beneficially alter their faecal microbiomes, which in the long term potentially leads to improved intestinal function, growth, and cognition. To test this we first need to know if consuming resistant starch results in changes in pH and SCFA in the large intestine as measured by faecal samples, a proxy for this internal environment.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 81602 0
Prof Balakrishnan S Ramakrishna
Address 81602 0
SRM Institutes for Medical Science No.1, Jawaharlal Nehru Salai, 100 Feet Road, Chennai, Tamil Nadu 600026
Country 81602 0
India
Phone 81602 0
+91 9994614890
Fax 81602 0
Email 81602 0
wurama@hotmail.com
Contact person for public queries
Name 81603 0
Ms Elissa Mortimer
Address 81603 0
3L:100, Flinders Centre for Innovation in Cancer GPO Box 2100 Adelaide SA 5001
Country 81603 0
Australia
Phone 81603 0
+61 8 8404 2840
Fax 81603 0
Email 81603 0
elissa.mortimer@flinders.edu.au
Contact person for scientific queries
Name 81604 0
Prof Balakrishnan S Ramakrishna
Address 81604 0
SRM Institutes for Medical Science No.1, Jawaharlal Nehru Salai, 100 Feet Road, Chennai, Tamil Nadu 600026
Country 81604 0
India
Phone 81604 0
+91 9994614890
Fax 81604 0
Email 81604 0
wurama@hotmail.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary