Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04015999 |
| Other study ID # |
PR-18073 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
November 1, 2018 |
| Est. completion date |
June 28, 2021 |
Study information
| Verified date |
June 2020 |
| Source |
International Centre for Diarrhoeal Disease Research, Bangladesh |
| Contact |
Tahmeed Ahmed, PhD, MBBS |
| Phone |
01713044799 |
| Email |
tahmeed[@]icddrb.org |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Background (brief):
Burden: A total of 52 million children under 5 are suffering from acute malnutrition
globally, of whom 33 million have moderate acute malnutrition (MAM). In Bangladesh, more than
2 million children suffer from MAM. According to Bangladesh Demographic Health Survey 2014
26%, 25% and 17% of children aged less than two years are stunted, underweight and wasted
respectively.
Knowledge gap: It has been already demonstrated that children with SAM have immature gut
microbiota that is partially corrected with treatment. Children with MAM have an increased
risk of mortality, infections and impaired physical and cognitive development compared to
well-nourished children. Although the global caseload of MAM is much greater than that of
SAM, the condition has not received the same level of attention or priority. Through our
previous and ongoing research we now know about the members of the gut microbiota that can
promote growth in children and also about certain food ingredients that promote the
proliferation of such beneficial microbiota. However, this knowledge needs to be applied on a
sufficiently powered community-based clinical trial.
Relevance: The rationale for this study is to assess whether long-term administration of
complementary food made of locally available food ingredients can stimulate the proliferation
of growth promoting members of the gut microbiota and have a positive impact on child growth.
Such a food (the microbiota directed complementary food; MDCF-2) has been identified through
our recently concluded Pre-proof of concept trial done on children with primary MAM. We would
now like to do a clinical community-based trial of this potential MDCF-2 in the management of
children with primary MAM.
Hypothesis: Complementary foods made of locally available food ingredients that stimulate the
proliferation of growth promoting gut microbiota (MDCF-2) will improve clinical outcomes.
Methods: We will conduct a proof of concept (POC) clinical trial in 12-18 months old children
with primary MAM (Weight-for-Length Z-score, WLZ between -2 and -3). This study will be
conducted at Bauniabadh, Radda MCH-FP (Maternal and Child Health- Family Planning) clinic,
Gabtoli of Mirpur area and possibly at the Special Nutrition Unit run by Terre des Hommes in
Kurigram. We will produce MDCF-2 at the icddr,b Food Processing Laboratory or nutrition
centre established at the site in sufficient quantities for clinical study. This formulation
will be matched in energy density and micronutrient content of ready-to-use supplementary
foods (RUSFs) used for MAM in Bangladesh and other countries, and will meet all other
requirements for a complementary/supplementary food for 12-18 months old children with MAM.
We will test MDCF-2 and the current RUSF standard of care for primary MAM to see the effect
on growth, proteomics and metabolomics of an intervention for 12 weeks, with a 4-week
post-intervention phase.
Hypothesis to be tested:
In a hypothesis testing research proposal, briefly mention the hypothesis to be tested and
provide the scientific basis of the hypothesis, critically examining the observations leading
to the formulation of the hypothesis.
Complementary foods made of locally available food ingredients that stimulate the
proliferation of growth promoting gut microbiota (MDCF) will provide a new way to improve
clinical outcomes, for example by improving growth of children with MAM.
Specific Objectives:
To investigate the efficacy of complementary food made of locally available food ingredients
that can stimulate the proliferation of growth promoting gut microbiota (Microbiota-Directed
Complementary Food; MDCF-2) in (i) promoting repair of microbiota immaturity (ii) promoting
proliferation of beneficial bacteria (iii) improving both ponderal and linear growth in
children (iv) improving the metabolomic profile with MAM
Description:
Background:
Moderate acute malnutrition (MAM), a major global health problem, is defined as wasting (i.e.
weight-for-height between < -2 and -3 Z-scores of the WHO Child Growth Standards) and/or
mid-upper-arm circumference (MUAC) greater or equal to 115 mm and less than 125 mm. According
to the Global Nutrition Report 2017, 8% or 52 million under-five children were acutely
malnourished globally in 2016. Stunting affected 23% or 155 million children. Approximately
one in 6 children under 5 years in South Asia suffered from MAM in 2013 (i.e. 17%). These
children are at increased risk of severe acute malnutrition (SAM), and have a three times
higher risk of mortality from common communicable diseases than the well-nourished peers.
Bangladesh has one of the highest childhood malnutrition burdens in the world. According to
Bangladesh Demographic Health Survey (BDHS) 2014, the prevalence of stunting among under-five
children is 36%, among them 12% suffer from severe stunting (Length-for-Age-Z score, LAZ
<-3). Around 15% of children are wasted (Weight-for-Length Z score, WLZ <-2); more than 2
million children suffer from MAM, while 3% or 450,000 children suffer from the deadly form of
SAM. Malnutrition costs Bangladesh an estimated US $1 billion a year. According to WHO
recommendations, infants and children aged 6-59 months with MAM need to consume
nutrient-dense foods to meet their extra needs for weight and height gain and functional
recovery. Currently there are no evidence-informed recommendations on the composition of
supplementary foods used to treat children with MAM. In situations of food shortage,
supplementary foods have been used to treat children with moderate acute malnutrition.
Interventions to address under nutrition should therefore include a strong component of MAM
management. MAM prevention should be taken into consideration in food security and other
development strategies as the situation becomes critical in populations where food insecurity
is rampant. Food insecurity has become a worldwide concern due to the increasing number of
people who remain undernourished amounting to 842 million, approximately 12% of the total
world's population. From the National Micro nutrient Status Survey in Bangladesh which we
conducted in 2011-12, severe insecurity of food was found most commonly in slum settlements
(17.2 %), compared to 12.3% at the national level, 12% in rural areas and 12.4% in urban
areas of the country. Since food insecurity cannot be overcome quite readily, it is important
therefore to develop interventions that depend upon locally available food ingredients and
are able to harness the beneficial power of the gut microbiota on infant and child growth.
One of the major factors limiting the impact of nutrition intervention is the inability of
the malnourished children to increase their intake to meet increased metabolic demands. In
collaborative studies between icddr,b and the Gordon Lab at Washington University in St.
Louis during the Jump start Phase of the Breast Milk, Microbiota and Immunity (BMMI) Project,
we applied Random Forests, a machine-learning-based approach, to bacterial 16S rRNA
(ribosomal ribonucleic acid) datasets generated from monthly fecal samples obtained from a
birth-cohort of children living in an urban slum of Dhaka, Bangladesh. These children
exhibited consistently healthy growth (WLZ -0.32+0.98). Bacterial strains were identified
whose proportional representation defines a healthy gut microbiota as it assembles during the
first 2-3 postnatal years. In a randomized clinical trial at icddr,b of two therapeutic foods
(imported ready-to-use therapeutic food [RUTF (Ready to Use Therapeutic Food), Plumpy'Nut]
versus locally prepared rice/lentil-based Khichuri and Halwa) in Bangladeshi children with
severe acute malnutrition (SAM), it was observed that the microbiota immaturity is
incompletely and only transiently improved, with children remaining markedly stunted and
underweight throughout the follow-up period. Bangladeshi children with MAM also exhibited
significant microbiota immaturity, although less severe than children with SAM. Microbiota
immaturity thus serves as a potential biomarker to identify infants at risk for
undernutrition and to monitor treatment and prevention strategies.
Investigators recently developed ready-to-use therapeutic foods using locally available food
ingredients-rice, lentil, and chickpeas that are culturally relevant and acceptable. They
found through a double-blind RCT (Randomized Controlled Trial) that chickpea-based and
rice-lentil-based RUTF were as effective as the commercial peanut based-RUTF and well
accepted by children with SAM. Through a combination of the above mentioned RCT and clinical
translational studies, they have identified growth promoting age-discriminatory beneficial
microbiota and locally available food ingredients that support proliferation of these
beneficial microbiota. Besides, results of earlier studies done on gnotobiotic animals in
Washington University Centre for Genome Science has led us to suggest that a combination of
food ingredients (chickpea, soy flour, peanut and green banana) will be worth studying with
respect to the diet's impact on stimulating proliferation of growth-discriminatory microbiota
as well as cost and sustainability. To assess the degree to which the results obtained from
the gnotobiotic mouse and piglet models translate to humans, investigators recently performed
a RRC (Research Review Committee) and ERC (Ethecial Review Committee)approved study, icddr,b
protocol (PR-16099) 'Pre-Proof of Concept clinical trials to optimize lead
microbiota-directed complementary food (MDCF) prototypes for their ability to repair
microbiota immaturity and establish their organoleptic acceptability 'and successfully
completed the study. This study was designed to test the effects of three locally produced
MDCF prototypes (MDCF-1, MDCF-2 and MDCF-3) and a locally produced rice-lentil-based RUSF.
The objective of this pilot study was to demonstrate a Pre-proof of Concept that certain
complementary foods would have a beneficial effect on young children suffering from moderate
acute malnutrition by stimulating the proliferation of particular members of the gut
microbiota that are known for their growth promoting effect. In that pilot study they
investigated microbiota-for-age Z score as well as the impact of the proliferation of good
members of the gut microbiota on certain body systems. The results of the Pre-POC pilot trial
conclusively showed that one of the three microbiota directed complementary foods namely
(MDCF-2; composed of a combination of chickpea, soy flour, peanut, green banana, oil, sugar
and micronutrients) was associated with increased levels of certain amino acids, that have a
key role in development of the long bones, development of the brain and increased production
of IGF-1. This was done using the state-of-the-art DNA aptamer based SomaLogic scan. And the
results suggest that this candidate MDCF-2 is effective in stimulating the growth of growth
promoting members of the gut microbiota, for example Faecalibacterium prausnitzii. Thus,
MDCF-2 promotes gut microbiota that induces the hormone insulin-like growth factor 1 (IGF-1),
which promotes bone growth and remodelling.
Based on this evidence investigators would now like to do a much larger clinical trial using
the most promising MDCF which is MDCF-2 with the primary end point being linear growth. This
trial would be on children with primary MAM.
Research Design and Methods Investigators will conduct a clinical trial among 12-18 months
old children with primary MAM (WLZ <-2 to -3).
Study design: Randomized controlled intervention trial. Study site: This study will be
conducted at Bauniabadh, RADDA MCH-FP (Maternal and Child Health - Family Planning) clinic in
Mirpur area and Gabtoli of Dhaka city, and possibly at the Special Nutrition Unit run by
Terre des Hommes in Kurigram.
Study participants: The study participants will be 12-18 months old children of either sex
with MAM (WLZ <-2 to -3).
Initial screening and enrolment: Children will be screened and enrolled through household
surveys by Field Research Assistants (FRAs) following pre-specified inclusion criteria.
Fulfilling the enrollment criteria and upon receiving the consent for study participation
from the parents or legal guardians, the children with the respective mother/caregiver will
be enrolled and randomly assigned to one of the two arms according to computer-generated
random numbers. The code of assigned type of diet will be kept in closed opaque envelopes for
each individual, and will be opened only when the caregiver signs the consent form.
Study design:
Arm 1 - Rice-lentil based RUSF (rationale: reference standard of care for MAM; based on
knowledge of its effects on the gut microbiota or microbiota immaturity) Arm 2 - MDCF2
(Microbiota Directed Complementary Food 2) with four complementary food ingredients
(rationale: lead with evidence from Pre-POC clinical trials to optimize lead
microbiota-directed complementary food prototypes for their ability to repair microbiota
immaturity and positive effects on growth) Fecal sample collection Weekly fecal samples
(1-2g) will be collected within 30 minutes of excretion (at home and transported back to the
icddr,b) using the liquid nitrogen containing dry shipper. Specimens will be stored at -80°C
before being sent to the Gordon Lab analysis of microbiota maturity (measured before, during
and after cessation of treatment with MDCF and RUSF) and PCR (Polymerase Chain
Reaction)-based assessment of enteropathogen burden in fecal samples (measured before and
after MDCF treatment).
1-2 gm of fecal samples will be collected from each child at enrollment, weekly during the
1st month of intervention, and 4 weekly during the 2nd and 3rd month of intervention and at
the end of post-intervention phase. Assuming 62 study participants /arm, a total of 992 fecal
specimens will be collected in this study. 2 gm of faecal samples will be collected from
mothers at the time of enrollment.
Urine sample collection 2 mL of urine samples will be collected from each child at
enrollment, one week after enrollment and monthly once in the intervention and
post-intervention phases. Assuming 62 study participants /arm, a total of 744 urine samples
will be collected in this study. 5 mL of urine samples will be collected from mothers at the
time of enrollment.
Blood sample collection 2 mL of blood samples each will be collected from each child prior to
intervention, end of first month of intervention and just after the intervention is complete.
A total of 372 plasma samples will be collected in this study. 5 mL of blood samples will be
collected from mothers at the time of enrollment.
Maternal nutritional status is associated with child nutritional status, as shown through the
results of our eight country MAL-ED (Malnutrition and Enteric Diseases) study. In addition,
neonatal and other maternal factors were early determinants of lower length-for-age, and
their contribution remained important throughout the first 24 months of life.9 The other
maternal factors, investigators believe, would include maternal gut microbiota as well as
maternal blood amino acid profile. Initiatives to address childhood stunting should also
consider improvements to the composition of complementary foods (i.e., higher protein) and
strategies to reduce gut pathogen exposure. As such, they will record maternal height and
weight. In order to understand the biological state of nutrition of the mother, enrolment
samples of stool, blood and urine will be asked of the mother. These samples will be analyzed
for gut microbiota, and proteomics, and the results correlated with those of the enrolled
children.
Feeding sessions The children and mothers/caregivers will be requested to come to the
nutrition centers established at the sites preferably between 9-11 am and 3-5 pm on day 1.
The mothers will be requested not to give any food and breast milk in the 2 hours preceding
the observed meal time. The child will be offered 25 grams of MDCF or RUSF as decided by
random allocation in each of the two meals between 9-11 am and 3-5 pm. The mothers will be
asked to spoon feed the pre-weighed diets to their children until s/he refuses to eat, as
described below. After a two-minute pause, the same diet will be offered a second time until
s/he refuses again. After a second two-minute pause, the diet will be offered a third time
until refused again. After this third refusal, the feeding episode will be considered as
'terminated'. The duration of the feeding (excluding the intervening 'rest periods') will be
recorded by stopwatch, and the total duration of the feeding will be noted. This feeding
episode will last for maximum 60 minutes. Measured volumes of plain water will also be given
and the amount of water taken during this meal period of 60 minutes will be measured. The
feeding episode will take place under the direct supervision of trained study personnel.
Children will be considered as refusing further intake if they move their head away from the
food, cry, clamp the mouth or clinch the teeth, or become agitated, spit out the food or
refuse to swallow. The amount of MDCF/RUSF actually ingested will be calculated by
subtracting the left over from the offered amount. Pre-weighed napkins will be provided; any
food that is regurgitated, vomited or spilled will be swabbed, weighed and subtracted from
the amount offered. The amount of consumed food (g), energy (kcal) and category of
acceptability will be analyzed. The enrolled children will be monitored daily by Field
Research Assistants for any possible side effects/adverse events (e.g. rash, urticaria due to
food allergy or any significant changes in clinical status) for a week. If any side
effects/adverse events are observed, they will be treated according to standard of care. A
standardized production procedure will be followed to control the quality of RUSF and MDCF
following international standard protocol. RUSF and MDCF will be prepared at the food
processing laboratory. Preparation of food under different steps, that is, roasting, particle
size reduction, homogeneous blending, and supplying to the nutrition centres will be
monitored by icddr,b investigators. Food will be prepared everyday to ensure that no
unexpected contamination and nutrient losses occur during preparation. Although raw food
ingredients will be very carefully procured from the local market and stored in reasonable
quantities, investigators will prepare, dispense, and feed the children the same day the MDCF
and RUSF are prepared. Every child will be offered 25gm of the diet twice daily at the
feeding center for the first 4 weeks. In the following month, the child will be offered 25gm
of the diet at the feeding center and additional 25gm will be provided in a clean container
to feed at home. In the third month, two separate containers containing 25gm diet will be
provided every day to each enrolled child at participant's home.
In this study nutritional status will be assessed through anthropometry, comparing with WHO
growth reference standards. At the beginning of the study, information will be sought on the
demographic characteristics (families' wealth, standard of housing, family structure and
parental characteristics etc.), and FRAs will record the children's weight using a digital
scale with 2g precision (Seca, model 728, Germany), length (using infantometer, Seca, model
416, Germany), and mid upper-arm circumference to the nearest mm (using a non-stretch
insertion tape). Anthropometrics will be done according to the standard procedures and all
measurements will be taken thrice and the middle one will be recorded.
All interventions in each study will be administered to children at the Mirpur health
clinic/RADDA clinic or in Kurigram. Mothers/primary caregivers will be advised to maintain
their child's current dietary and breastfeeding practices.
Investigators will complete enrollment within 12 months and the follow up as well as data
analysis within an additional 6 months. However, this trial on primary MAM will continue
simultaneously with the other clinical trial on Post SAM-MAM that will have a longer period
of duration.
Recruitment, Screening and Consenting Census, screening, enrolment of study participants will
be done in the catchment areas of the sites in Dhaka city and in Kurigram. Parents of
children who meet the MAM criteria (for Primary MAM trial) will be approached about
enrollment into the study. A Field Research Assistant will explain the study in detail,
answer any questions from the parent(s), and invite the parent(s) to enroll the child in the
study.
At the beginning of the study, information will be sought on the demographic characteristics
(families' wealth, standard of housing, family structure and parental characteristics etc.),
and FRAs will record the children's weight using a digital scale with 2 g precision, length
(using infantometer,), and mid-upper-arm circumference to the nearest mm. Study participants
will be asked to come directly to the nutrition center for nutritional therapy.
Preparation of MDCF 2 and RUSF Based on compatible combinations of complementary food
ingredients identified in the Pre-POC study described above, MDCF2 as well as Rice-lentil
RUSF will be produced at the icddr,b Food Processing facility in Mirpur and in Kurigram (to
be established in both places) in sufficient quantities for clinical study. The two diets
will be matched in energy density and micronutrient content. The energy density of MDCF is
125 kcal/25 g (per serving), and caloric distribution is targeted to be 45-50 percent from
fat and 8-10 percent from protein. Experiments in development of the MDCF prototypes and
assessment of the organoleptic properties have been done during the Pre-POC clinical trial.
After receiving the raw materials (rice/lentil/chickpea) the foreign materials/grains or
seeds (if there is any) will be taken out, and then in an open pan the raw materials will be
roasted. The temperature will be maintained at 120-130°C for roasting. Usually it takes 8-10
minutes for roasting 100g of each raw material. Continuous stirring is essential to ensure
roasting of single seeds/grains. After completion of roasting it will be kept aside for
cooling and then will be grinned. Finally the pre-weighed premix powder will be added. The
processing of whole green banana for inclusion in MDCF2 is different from the other
ingredients. Green banana with skin will be placed in a deep pan in boiling water
(100°C-110°C) and boiled for about 17-20 minutes until they are cooked and tender. The skin
of the green banana will be peeled off and the edible white part would be taken and grated
into small pieces. Then they will be taken in a pot and allowed to cool. The small pieces of
banana will be smashed with spoon/hand crusher. The weights of all other ingredients will be
recorded. Recipes will be produced in small batches by mixing all ingredients in an electric
blender. A small amount (1 percent) of soy lecithin shall be added to the recipe in order to
improve the consistency and prevent oil separation.
Anthropometry The age of the child will be verified against documentation (birth certificate
or immunization card, if available) or caregiver's report of the child's birth date. Length
will be measured by a infantometer sensitive to 0.1 cm. Body weight will be measured by a
balance sensitive to 2g. Length-for-age (LAZ), weight-for-length (WLZ) and Weight-for-Age
(WAZ) Z-scores will be calculated following the Multicentre Growth Reference Study (MGRS) WHO
(World Health Organization) growth standards. Edema will be examined by pressing the upper
side of both feet for 3 seconds. Mid-upper arm circumference (MUAC) will be measured using
MUAC tape (UK). Regular standardization of the measuring equipments will be done using
standards.
Analyses of plasma and fecal samples Plasma samples collected from this trial will be sent to
Dr Jeffrey Gordon's lab in the Center for Genome Sciences and Systems Biology at Washington
University in St. Louis. Advanced mass spectroscopic- and immunoassay-based methods will be
used to obtain new knowledge about the role of gut microbiota immaturity and the effects of
attempting acute repair of this immaturity with lead microbiota-directed complementary food
(MDCF) on biomarkers and mediators of healthy growth. Comparisons will be made with the
control group (i.e., those consuming reference RUSF standard). Targeted Ultra Performance
Liquid Chromatography-Mass Spectrometry (UPLC-MS) and Gas Chromatography-Mass Spectrometry
(GC-MS) will be used to profile analytes of specific interest in plasma and/or fecal samples
including bile acids and short chain fatty acids (SCFAs); markers of mitochondrial function
(e.g., β-hydroxybutyrate, acylcarnitines/acylCoAs, TCA cycle intermediates); amino acids in
serum plus fecal samples [branch chain amino acids, tryptophan and tryptophan metabolites
related to growth and inflammatory status, including those produced by bacterial tryptophan
metabolism (e.g. indole acetic acid derivatives)]. Key mediators/biomarkers of linear growth
(e.g., growth hormone and IGF-1), energy utilization (insulin, leptin), and bone biology
[IL-6 (Interleukin-6), osteoprotegerin, the C-terminal peptide of type I collagen (CTX, a
marker of osteoclast activity/bone resorption), and the amino-terminal propeptide of Type 1
procollagen (P1NP, a marker of osteoblast activity/bone formation)], and systemic
inflammation (CRP, AGP) will be quantified using established ELISA/Luminex assays. Proteins
in blood will be identified using the SOMAlogic scan that permits identification of more than
1300 different proteins. The proteomic study done on plasma samples from children with SAM in
our previous Pre-POC trial done in Dhaka has already demonstrated a number of significant and
clinically relevant associations between certain proteins and clinical phenotypes using the
SOMAlogic scan.
Information gathered will be used to select human fecal samples for transplantation into
germ-free animals in the Gordon Lab in St Louis; these animals, who will be fed the diets of
their human microbiota donors, will be used to further characterize the mechanisms that link
MDCF prototypes, the gut microbiota, and host physiology/metabolism. In addition, these
plasma and fecal biomarkers will be used to determine that MDCF promotes repair of microbiota
immaturity and improves biological state in children.
Sample Size Calculation In the pre-POC trial of different MDCFs, the baseline
weight-for-length Z score of children who received MDCF2 was -2.2 and after one month of
supplementation was -1.7. If it is considered the WLZ -2 at baseline and -1.7 at end line,
pooled SD (Standard Deviation)as 0.53 then the sample size is 49 in each arm at 80% power and
5% level of significance.
With 20% attrition 62 children will be required to be enrolled in each arm. Therefore, for
the Primary MAM trial, 62 children will receive MDCF2 and 62 children will receive
Rice-lentil RUSF.
Data Analysis The two groups of children with MAM will be compared at baseline and at
different time points. All analytes mentioned in the section Analyses of plasma and fecal
samples' will be compared between MDCF2 and RUSF groups.
Data Safety Monitoring Plan (DSMP) Data collection tools for this study will include case
report forms, laboratory worksheets and source documentation. Complete source documentation
(study visits, laboratory reports, etc.) will be kept for each study participant in
individual study charts. All laboratory specimens, reports, study data collection and
administrative forms will be identified by coded number to maintain study participant
confidentiality and to enable tracking throughout the study.
Forms, lists, logbooks, appointment books, and any other listings that link study participant
ID (Identification) numbers to other identifying information will be stored in a separate,
locked file in an area with limited access. All information regarding study participants will
be kept in password-protected computer files or in locked file cabinets that can be accessed
only by authorized study personnel. Chart information and information from study records will
not be released without written permission from the study participant's parent(s). However,
records may be reviewed by representatives from the Research Review Committee and Ethical
Review Committee of icddr,b.
The study investigators are responsible for ensuring complete and accurate documentation for
the study and for each study participant, including: medical records, records detailing each
study participant's progress through the study, laboratory reports, Case Report Forms (CRFs),
signed informed consent forms, correspondence with IRB (Institutional Review Board ), adverse
event reports, and information regarding participant discontinuation and completion of the
study. All required data will be clearly and accurately recorded in the CRFs by authorized
study personnel. Only designated study-site personnel who have received appropriate training
will record or change data in a CRF. The investigators are responsible for procuring the data
and for quality of data recorded in the CRFs. Data entry and management will be performed at
icddr,b.
Ethical Assurance for Protection of Human rights The study will be started after obtaining
IRB approval by the icddr,b Research Review Committee and Ethical Review Committee. Before
enrolment in the study, informed written consent will be taken from the legal guardian of the
study participants. The privacy, anonymity and confidentiality of data/information
identifying the study participants will be strictly maintained. Personal identifications
taken during enrolment and other study procedures will be kept under lock and key. None other
than the study personnel will have access to information of personal identification and other
sensitive information.
Expected risks/adverse events for this protocol are those related to blood sample collection,
fecal sample collection and feeding of microbiota directed complementary food. None of these
qualify as a serious adverse event (SAE). Expected Adverse Events (EAEs) related to blood
draw are as follows:
- discomfort
- pain
- introduction of infection
- bleeding
- fainting or bruising
- Precaution will be taken to avoid introduction of infection by disinfecting the
site of venipuncture and using sterile equipment
- The risk of bleeding and bruising will be minimized by immediate application of
pressure after venipuncture
- The participant (child) will be in the sitting or supine position during blood
draws to avoid injuries from fainting
All possible adverse events will be treated appropriately. These will include:
- Vomiting
- Diarrhoea
- Skin rash
- Urticaria from food allergy
- Abdominal distension
- Pain abdomen Assessment of Adverse Events Both serious and non-serious adverse events
will be assessed for severity; relationship to study participation; actions taken; and
outcomes. All SAEs will be reported to the ERC of icddr,b within 24 hours of the site's
awareness of the event that will in turn be distributed to the sponsor. This will be
done by direct telephone communication, fax or e-mail.
Each category for AE assessment will be coded according to the following grading systems:
Severity:
1. Mild
2. Moderate
3. Severe
Relationship to Study Participation:
1. Definitely related: Clear cut temporal association, no other possible cause
2. Possibly related: Less clear cut temporal association, other causes possible
3. Unrelated: Independent of study, evidence exists that event is definitely related to
another etiology
Actions:
None Remedial therapy (more than one dose of medicine required) Permanently discontinued from
study participation Hospitalization Other Use of Animals Not applicable Collaborative
Arrangements This project is a collaborative effort between the investigators in the
Washington University School of Medicine and the International Centre for Diarrhoeal Disease
Research, Bangladesh (icddr,b). The clinical work, field activities will be undertaken in
Dhaka, Bangladesh, under the direct supervision of the Principal Investigator whereas the
laboratory analyses will be conducted at the Gordon Lab at Washington University in St.
Louis. All research units and the collaborating investigators have long histories of
international collaborations. All investigators have communicated during development of this
project and are committed to its successful implementation.
Facilities Available icddr,b has a well equipped Food Processing Lab that will facilitate
preparations of diet recipes. A number of project offices are located in Mirpur. More
importantly, an excellent rapport has been established with the community. The community
elite and elders are invited every year to a dissemination meeting so that they are aware of
the research being conducted.
Center for Genome Sciences, Washington University in St. Louis:
