Evaluation of Executive Function and Emotional Regulation in Children in Bangladesh
NCT ID: NCT05629624
Last Updated: 2022-11-29
Study Results
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Basic Information
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UNKNOWN
NA
280 participants
INTERVENTIONAL
2022-02-07
2024-08-31
Brief Summary
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Detailed Description
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Malnourished children have an abnormal assembly of the early gut microbiota which may impair brain function by disturbing the bidirectional neural and immune interactions between gut and brain by altered production of signal molecules by the microbiota such as short-chain fatty acids, and neurotransmitters. Nutritionally wasted children notably have marked brain atrophy on MRI and while re-feeding reverses brain atrophy, significant deficits remain in function and microstructure. It is likely that the anatomic reconstitution of the brain with feeds designed principally for corporal rapid catch-up growth results in brain structure which is unable to provide substrate for normal cognitive and emotional performance. Fixing this must depend at least in part on provision of the appropriate nutrients in amounts that meet demands during rapid catch-up growth of the body and brain.
The investigators propose that nutrient deficiencies, and gut microbiome dysbiosis both induce structural and functional abnormalities of the brain in malnutrition that lead to neuropsychological sequelae in childhood and later life. The human brain develops during intrauterine life as well as early childhood, especially in the developmental window between birth and 3 years of age. Better recovery of brain architecture and function in children suffering malnutrition will result from augmenting feeds with key nutrients with targeted functionality in the brain during rapid brain regrowth. The supplements are E-RUSF (Ready to Use Therapeutic Feed-enhanced manufactured by Nutriset) and E-SQLNS (standard/enhanced small quantity lipid based nutrient supplements) all containing key nutrients for rehabilitating wasted brains: 24 micronutrients (vitamins and minerals) provided at recommended daily allowance levels, functional lipids (Long Chain Polyunsaturated Fatty Acids DHA and EPA), sialylated milk oligosaccharides, neural specific antioxidants (zeaxanthine, lutein; crypto-xanthine) and microbiome modulating dietary soluble fibre mix (inulin + FOS), 6 g per 26g daily dose of E-SQLNS, as well as within a daily 100g ration of E-RUSF. The comparator group will receive standard of care therapeutic feeds in Bangladesh. These feeds are an energy dense chickpea-based RUSF with a targeted calorie delivery of 250 kcal/50 g (per serving) with caloric distribution 45-50 percent from fat and 8-10 percent from protein.
The diagnostic criteria for MAM in children 6 to 59 months of age are weight-for-height z-score \<-2 and ≥-3 z-score of WHO child growth standards and/or MUAC \<12.5 and ≥11.5 cm. This definition is also supported by USAID. There are about 1.8 million children under 5 years of age in Bangladesh with MAM. The study will be conducted in the Mirpur area within the Dhaka city. The Mirpur study/surveillance area is well known to all staff working in the Mirpur field clinic as they have been working in this area on existing studies for the last 10 years. The investigators have established a field clinic/lab located within ward 5 where staff have been working for the BEAN project (PR-14110 and PR-18036) for the last 7 years. Existing staff will therefore recruit the children and mothers from the study area. The Mirpur area is a densely populated area and is located around 8 km from the main campus of icddr, b at Mohakhali, Dhaka. Mirpur was selected as the study site because it is inhabited by poor and middle-class families, residential and sanitary conditions are typical of any congested urban settlements, and there have been ongoing research activities in this area for the last 30 years.
This study design will adequately assess the capabilities of the EF/ER Toolkit in the control group allowing comparisons to high-income country data. Through the two interventional arms, and the comparison to 3y old untreated children, there will be high quality pilot data on the EF/ER response to interventions to power a definitive trial. The enrolled children will have follow-up visits at 2 years and 3 years of age with EF/ER for developmental assessment.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
HEALTH_SERVICES_RESEARCH
NONE
Study Groups
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Chickpea based RUSF
Locally produced ready to use supplementary food (RUSF), 50 g/packet contains 204 kcal energy). Two packets of RUSF provided for consumption at a rate of 50-100 kcal/kg/day till the child's weight for height returns to normal (WHZ \>-1SD) or for maximum 3 months.
Chickpea based RUSF
One group will receive locally produced RUSF, approximate at 50-100 kcal/kg/day, two of 50g packets daily (42) until anthropometric recovery ( WHZ \> - 1SD) has been achieved or for maximum 3 months then immediately 1 packet / day SQLNS will be given throughout the study till the end of 2 years of follow-up.
E-RUSF
Enhanced Ready to use therapeutic feeds (E-RUSF), 50-100 kcal/kg/d daily until for anthropometric recovery (WHZ \> - 1SD) is achieved or for maximum 3 months then E-SQLNS will be given till the end of 2 years follow-up.
E-RUSF
The other group will receive the E-RUSF at 50-100 kcal/kg/day which in this age group approximates one 92 g sachet daily until anthropometric recovery ( WHZ \> - 1SD) has been achieved or for a of maximum 3 months, then immediately E-SQLNS 1 packet daily provided throughout the study till the end of 2 years of follow-up.
Well-nourished children
Well-nourished children at 1 year of age (WLZ/WHZ score \>-1 SD). No nutritional or psychosocial intervention. Only follow-up.
No interventions assigned to this group
Outcome reference group
3 year olds previously untreated MAM children (WHZ \<-2 and ≥-3 z-score, and/or MUAC \<12.5 and ≥11.5 cm) and free from any acute illness will be used as the outcome reference group.
Outcome reference group/RUSF
We will also recruit 70 three-year-old previously untreated MAM children WHZ \<-2 and ≥-3 z-score, and/or MUAC \<12.5 and ≥11.5 cm as an outcome reference group for a singular assessment. All children (both case \& control) will undergo a baseline nutritional, medical, biological and neuropsychological assessment (EF, ER, EEG and fNIRS). After all the assessments chick-pea based RUSF will be given for 2 months for nutritional rehabilitation.
Interventions
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Chickpea based RUSF
One group will receive locally produced RUSF, approximate at 50-100 kcal/kg/day, two of 50g packets daily (42) until anthropometric recovery ( WHZ \> - 1SD) has been achieved or for maximum 3 months then immediately 1 packet / day SQLNS will be given throughout the study till the end of 2 years of follow-up.
E-RUSF
The other group will receive the E-RUSF at 50-100 kcal/kg/day which in this age group approximates one 92 g sachet daily until anthropometric recovery ( WHZ \> - 1SD) has been achieved or for a of maximum 3 months, then immediately E-SQLNS 1 packet daily provided throughout the study till the end of 2 years of follow-up.
Outcome reference group/RUSF
We will also recruit 70 three-year-old previously untreated MAM children WHZ \<-2 and ≥-3 z-score, and/or MUAC \<12.5 and ≥11.5 cm as an outcome reference group for a singular assessment. All children (both case \& control) will undergo a baseline nutritional, medical, biological and neuropsychological assessment (EF, ER, EEG and fNIRS). After all the assessments chick-pea based RUSF will be given for 2 months for nutritional rehabilitation.
Eligibility Criteria
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Inclusion Criteria
* Child age 12-15 months or 36-39 months of age
* WHZ \<-2 and ≥-3 z-score, and/or MUAC \<12.5 and ≥11.5 cm and free from any acute illness
* Mother agrees to feed their children a study diet at home.
* Mother willing to bring the child to the clinic for assessment (morbidity, nutrition history, adherence to treatment, anthropometry and advice to mother on parenting) and clinical examination.
* Mother will agree to provide her biological samples
* Mother willing to have a child undergo biological sample collection and neuropsychological assessment at baseline (1-year-old) and at ages 2 years and 3 years at the clinic.
* Family has no plan to move from the study area in the next three years.
* Mother willing to sign consent form
* Child age 12-15 months
* WHZ score \> -1 and free from any acute illness
* Mother willing to bring the child to the clinic for assessment (morbidity, nutrition history, adherence to treatment, anthropometry and advice to mother on parenting) and clinical examination.
* Mother will agree to provide her biological samples (see below).
* Mother willing to have a child undergo biological sample collection and neuropsychological assessment at baseline at 1 year old and again at 2 years and 3 years at the clinic.
* Family has no plan to move from the study area in the next two years.
Exclusion Criteria
* Congenital anomaly.
* Mother who is not willing to feed the rehabilitation feed or the small quantity supplement to her child.
* Family will not stay 3 years in the study area.
* Mother who is not willing to sign a consent form.
* Child age \>15 months or \< 12m.
* Mother who is not willing to feed the rehabilitation feed or the small quantity supplement to her child.
* Family will not stay 3 years in the study area.
* Any congenital anomaly.
12 Months
39 Months
ALL
Yes
Sponsors
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The University of The West Indies
OTHER
International Centre for Diarrhoeal Disease Research, Bangladesh
OTHER
University of Auckland, New Zealand
OTHER
Wellcome Trust
OTHER
Boston Children's Hospital
OTHER
Responsible Party
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Charles Alexander Nelson III
Professor of Pediatrics and Neuroscience
Principal Investigators
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Charles Nelson, Ph.D
Role: PRINCIPAL_INVESTIGATOR
Children's Hospital Boston/Harvard University
Terrence Forrester, Dr
Role: PRINCIPAL_INVESTIGATOR
University of the West Indies
Locations
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International Centre for Diarrheal Disease Research
Dhaka, , Bangladesh
Countries
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Central Contacts
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Facility Contacts
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References
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Other Identifiers
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M4EFaD/Dhaka PR-21084
Identifier Type: -
Identifier Source: org_study_id
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