ANZCTR - Registration

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]

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

Gut dysbiosis

Stunting

Condition category

Condition code

Oral and Gastrointestinal

Normal oral and gastrointestinal development and function

Diet and Nutrition

Other diet and nutrition disorders

Oral and Gastrointestinal

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]

Prevention

Comparator / control treatment

No control group

Control group

Uncontrolled

Outcomes

Primary outcome [1]

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]

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]

Acetate concentrations of stool samples measured using GC-FID (Gas Chromatography with Flame Ionization Detector.)

Timepoint [1]

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]

Butyrate concentrations of stool samples measured using GC-FID (Gas Chromatography with Flame Ionization Detector.)

Timepoint [2]

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]

Propionate concentrations of stool samples measured using GC-FID (Gas Chromatography with Flame Ionization Detector.)

Timepoint [3]

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]

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]

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

Sex

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

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

5/06/2017

Date of last participant enrolment

Anticipated

Actual

9/10/2017

Date of last data collection

Anticipated

Actual

18/12/2017

Sample size

Target

40

Accrual to date

Final

39

Recruitment outside Australia

Country [1]

India

State/province [1]

Tamil Nadu and Odisha states.

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Bill & Melinda Gates Foundation

Country [1]

United States of America

Funding source category [2]

Government body

Name [2]

Biotechnology Industry Research Assistance Council (BIRAC)

Country [2]

India

Primary sponsor type

University

Name

SRM Institutes for Medical Science

Country

India

Secondary sponsor category [1]

University

Name [1]

Flinders University

Country [1]

Australia

Secondary sponsor category [2]

Other Collaborative groups

Name [2]

South Australian Health and Medical Research Institute (SAHMRI)

Country [2]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Southern Adelaide Clinical Human Research Ethics Committee

Ethics committee address [1]

Office for Research
Corporate Services
Southern Adelaide Local Health Network
Ward 6C, Room 219, Flinders Medical Centre
Bedford Park 5042

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

19/07/2016

Approval date [1]

17/11/2016

Ethics approval number [1]

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

Public notes

Contacts

Principal investigator

Name

Prof Balakrishnan S Ramakrishna

Address

SRM Institutes for Medical Science No.1, Jawaharlal Nehru Salai, 100 Feet Road, Chennai, Tamil Nadu 600026

Country

India

Phone

+91 9994614890

Email

[email protected]

Contact person for public queries

Name

Elissa Mortimer

Address

3L:100, Flinders Centre for Innovation in Cancer GPO Box 2100 Adelaide SA 5001

Country

Australia

Phone

+61 8 8404 2840

Email

[email protected]

Contact person for scientific queries

Name

Balakrishnan S Ramakrishna

Address

SRM Institutes for Medical Science No.1, Jawaharlal Nehru Salai, 100 Feet Road, Chennai, Tamil Nadu 600026

Country

India

Phone

+91 9994614890

Email

[email protected]

Trial Review

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