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Trial registered on ANZCTR


Registration number
ACTRN12618000182291
Ethics application status
Approved
Date submitted
19/01/2018
Date registered
5/02/2018
Date last updated
5/02/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Effect of resistant starch on fecal pH, short chain fatty acid concentrations, and gut bacteria in a cohort of normal and stunted children in southern India.
Scientific title
Effect of native and acetylated high amylose maize starch on fecal pH, short chain fatty acid concentrations, and microbiota in a cohort of normal and stunted children in southern India.
Secondary ID [1] 293824 0
Nil known
Universal Trial Number (UTN)
U1111-1208-1478
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Environmental Enteropathy 306246 0
Growth faltering/stunting 306248 0
Gut dysbiosis 306254 0
Condition category
Condition code
Oral and Gastrointestinal 305347 305347 0 0
Normal oral and gastrointestinal development and function
Diet and Nutrition 305348 305348 0 0
Other diet and nutrition disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Resistant starch as High Amylose Maize Starch (HAMS) was fed to participants for 2 weeks at 10 grams per day followed by normal diet during the 2 week 'washout' period and then a further 2 weeks of 10 grams per day of Resistant Starch as Acetylated High Amylose Maize Starch (HAMSA). The HAMS and HAMSA were incorporated into biscuits and consumed daily by participants under the supervision of study staff.
Intervention code [1] 300081 0
Prevention
Comparator / control treatment
Active control. Participants acted as their own control with measurements taken at both baseline (before any intervention commenced) and during the washout period in between the intervention periods.
The comparator is both the control and HAMSA and statistical analysis were undertaken separately for both. This enabled us to determine the effect of each individual starch (HAMS or HAMSA) compared to baseline and washout as well as compared to each other for their separate intervention periods.
Control group
Active

Outcomes
Primary outcome [1] 304497 0
pH of fecal samples
Timepoint [1] 304497 0
Assessments of this outcome will occur at day 0 before any feeding intervention and then on 12 subsequent occasions at 3-4 day intervals for 6 weeks.
The primary timepoints are multiple because more than one intervention is being tested (HAMS and HAMSA). Primary timepoints are therefore as follows:
Day 15-End of 14 day HAMS feeding intervention
Day 44-End of 14 day HAMSA feeding intervention
Secondary outcome [1] 342142 0
Concentration of short chain fatty acids (acetate, butyrate and propionate) measured in fecal samples.
Timepoint [1] 342142 0
At days 0 before any feeding intervention and then on 12 subsequent occasions at 3-4 day intervals for 6 weeks.
Secondary outcome [2] 342143 0
Relative abundance of microbiota in fecal samples was determined as follows: Fecal microbiome analysis was performed on fecal samples from a subset of subjects (3 healthy and 3 stunted children). Four fecal samples each were selected from each subject representing basal (day 0), end of HAMS feeding (day 15), end of washout period (day 29), and end of HAMSA feeding (day 44). . Fecal DNA was extracted using PowerSoil DNA isolation kits (Mo Bio Laboratories, Carlsbad, CA, USA) with the modifications as per HMP Manual of Procedures 2010. DNA extracts were treated with RNAse A (PureLink #12091-021, Invitrogen Bioservices, Bangalore, India),, quality checked by electrophoresis and 260/280 ratio on a Nanodrop spectrometer, and quantified fluorimetrically (Qubit, Invitrogen Bioservices, Bangalore, India). One microgram of DNA was fragmented in the range of 300 to 400 bases, and libraries prepared using TruSeq DNA sample preparation kit v2 (Illumina, San Diego, CA, USA) as per manufacturer’s instructions. Twenty four samples of DNA from each of the stool samples were subjected to paired end 100 cycle whole genome sequencing using an Illumina Hiseq 1000 platform at the Centre for Cellular and Molecular Platforms, Bangalore, India. Libraries were sequenced in a paired end 100 base run, using TruSeq SBS Kit v3-HS (FC-401-3001, Illumina, San Diego, CA, USA) according to manufacturer recommended protocols.
Timepoint [2] 342143 0
At days 0 before any feeding intervention and then on 12 subsequent occasions at 3-4 day intervals for 6 weeks.
Secondary outcome [3] 342144 0
Bacterial short chain fatty acid biosynthesis gene profile was determined using bioinformatic processing of shotgun metagenomic sequence data as follows: Illumina paired-end reads were adapter- and quality-filtered using Trimmomatic v0.32, resulting to an average of 248 ± 158 million (mean ± s.d.) reads for each sample. These interleaved reads were used for de novo assembly of contigs of at least 900 bp with IDBA-UD v1.1.1. Gene prediction was performed using MetaGeneMark with genes less than 100 bp discarded. A non-redundant gene catalogue of 2,115,094 genes was constructed using CD-HIT and parameters “-c 0.95 –aS 0.9” (genes with greater than 95% identity and aligned length covering over 90% of the shorter gene were grouped together). The gene catalogue was annotated to the KEGG database (release 2017-04-17) using BLASTP with e-values = 1 × 10-5. High quality reads from each sample were aligned against the gene catalogue using SOAPAligner, and gene-length normalized read counts calculated using soap.coverage. Relative gene abundances were estimated by dividing gene-length normalized read counts by total sample mapped reads. The taxonomic characterization of each sample was determined by mapping high-quality reads from each sample to the clade-specific marker genes database of MetaPhlAn2.
Timepoint [3] 342144 0
At days 0 before any feeding intervention and then on 12 subsequent occasions at 3-4 day intervals for 6 weeks.

Eligibility
Key inclusion criteria
a) Children aged 2-5 years resident in a village in South India (30km from Vellore in the state of Tamil Nadu)
b) Weight for Height score (WHZ) between -2 and +2 standard deviations of World Health Organization standards.
c) Informed written consent obtained from parent
Minimum age
2 Years
Maximum age
5 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
a) Any chronic illness
b) Peripheral edema with WHZ <-2SD or >2 SD of WHO standards

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
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 either or both of the two feeding interventions, a sample size of 10 children was calculated for an alpha error of 5% and study power of 80%.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
5/03/2012
Date of last participant enrolment
Anticipated
Actual
21/03/2012
Date of last data collection
Anticipated
Actual
14/05/2012
Sample size
Target
10
Accrual to date
Final
20
Recruitment outside Australia
Country [1] 9501 0
India
State/province [1] 9501 0
Tamil Nadu

Funding & Sponsors
Funding source category [1] 298438 0
Charities/Societies/Foundations
Name [1] 298438 0
Bill & Melinda Gates Foundation
Country [1] 298438 0
United States of America
Primary sponsor type
University
Name
Flinders University
Address
Flinders Drive
Bedford Park,
South Australia, 5042
Country
Australia
Secondary sponsor category [1] 297580 0
University
Name [1] 297580 0
Christian Medical College
Address [1] 297580 0
Ida Scudder Road
Vellore
Tamil Nadu 632004
Country [1] 297580 0
India

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299433 0
Southern Adelaide Clinical Human Research Ethics Committee
Ethics committee address [1] 299433 0
Ethics committee country [1] 299433 0
Australia
Date submitted for ethics approval [1] 299433 0
16/01/2012
Approval date [1] 299433 0
01/03/2012
Ethics approval number [1] 299433 0
079.12
Ethics committee name [2] 299435 0
Institutional Review Board Christian Medical College
Ethics committee address [2] 299435 0
Ethics committee country [2] 299435 0
India
Date submitted for ethics approval [2] 299435 0
Approval date [2] 299435 0
19/01/2012
Ethics approval number [2] 299435 0
IRM Min No. 7681

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 2386 2386 0 0
/AnzctrAttachments/374332-Full approval letter FMC ethics.pdf (Ethics approval)
Attachments [2] 2387 2387 0 0
/AnzctrAttachments/374332-IRB Approval Updated 2012 Jan.pdf (Ethics approval)

Contacts
Principal investigator
Name 80386 0
Prof Balakrishnan S Ramakrishna
Address 80386 0
SRM Institutes for Medical Science
No.1, Jawaharlal Nehru Salai,
100 Feet Road,
Chennai, Tamil Nadu 600026
Country 80386 0
India
Phone 80386 0
+91 9994614890
Fax 80386 0
Email 80386 0
wurama@hotmail.com
Contact person for public queries
Name 80387 0
Elissa Mortimer
Address 80387 0
3L:100, Flinders Centre for Innovation in Cancer
GPO Box 2100
Adelaide
SA 5001
Country 80387 0
Australia
Phone 80387 0
+61 8 8404 2840
Fax 80387 0
Email 80387 0
elissa.mortimer@flinders.edu.au
Contact person for scientific queries
Name 80388 0
Balakrishnan S Ramakrishna
Address 80388 0
SRM Institutes for Medical Science
No.1, Jawaharlal Nehru Salai,
100 Feet Road,
Chennai, Tamil Nadu 600026
Country 80388 0
India
Phone 80388 0
+91 9994614890
Fax 80388 0
Email 80388 0
wurama@hotmail.com

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseEffect of native and acetylated dietary resistant starches on intestinal fermentative capacity of normal and stunted children in Southern India.2019https://dx.doi.org/10.3390/ijerph16203922
N.B. These documents automatically identified may not have been verified by the study sponsor.