Ignite Creation Date:
2024-05-06 @ 6:19 PM
Last Modification Date:
2024-10-26 @ 2:46 PM
Study NCT ID:
NCT05629624
Status:
RECRUITING
Last Update Posted:
2022-11-29
First Post:
2022-10-04
Brief Title:
Evaluation of Executive Function and Emotional Regulation in Children in Bangladesh
Sponsor:
Boston Childrens Hospital
Organization:
Boston Childrens Hospital
Study Overview
Official Title:
Multidimensional Evaluation of the Early Emergence of Executive Function and Emotional Regulation in Young Children in Bangladesh Using Nutritional and Psychosocial Intervention A Pilot Study
Status:
RECRUITING
Status Verified Date:
2022-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The study explores the impact of malnutrition at enrollment on executive function EF and emotional regulation ER in malnourished 1-year-old children and whether specially designed brain directed therapeutic feeds improve EFER outcomes at three years of age The study will detect changes in EF and ER related to nutritional rehabilitation using specially designed ready to use therapeutic feeds E-RUSF Nutriset during the repletion phase and maintained for two years until age 3 with enhanced E-SQLNS small quantity lipid based nutrient supplement also modified to provide adequate brain directed micro and macronutrients The investigators hypothesize that standard Bangladeshi designed B-RUSF and SQLNS Nutriset do not provide adequate nutrients to supply the brain during the rapid catch-up growth and subsequent early childhood growth phases of rehabilitation from Moderate Acute Malnutrition MAM The investigators predict that the children with moderately severe malnutrition treated with E-RUSF followed by 2 years of E-SQLNS will show an exuberance of connections higher functional connectivity than children receiving standard Bangladeshi rehabilitation feeds B-RUSF and SQLNS This prediction is based on past work using EEG to examine the BEAN sample in Bangladesh and differs from the sample in Boston where the investigators anticipate that among healthy normally nourished children greater connectivity will be associated with better cognitive outcomes The Core Toolkit will be deployed to the Bangladesh site to define its utility in prediction of executive dysfunction and emotional dysregulation in the context of low-income status malnutrition and nutritional intervention All nutritional intervention groups of malnourished children will also receive a set psychosocial stimulation curriculum that has been shown to be effective on severely malnourished children with therapeutic feedings
Detailed Description:
Malnutrition affects around 47 million children under 5 years of age annually and underlies 45 of the mortality in low- and middle-income countries where around 2 billion survivors suffer long term cognitive and behavioural sequelae Acute malnutrition comprising both MAM Moderate Acute Malnutrition and SAM Severe Acute Malnutrition causes 146 of all deaths of children under 5 years of age globally It is a significant problem in Bangladesh where 40 of under-fives have chronic or moderately acute malnutrition The long-term consequences of malnutrition for the 55 million children under 5 years that suffer from chronic malnutrition stunting or low height-for-age and the 14 are acutely malnourished wasting or low weight-for-height include poor brain development with resultant impairment of the development of cognitive motor and socio-emotional skills throughout childhood and adulthood Malnutrition during early childhood negatively affects cognition behaviour school performance and productivity in later life Further current rehabilitation feeding regimes do not reverse the impairment in brain development as these are designed with rapid catch-up growth as the principal goal
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 standardenhanced 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 kcal50 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 andor MUAC 125 and 115 cm This definition is also supported by USAID There are about 18 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 studysurveillance 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 cliniclab 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 EFER 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 EFER 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 EFER for developmental assessment
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 standardenhanced 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 kcal50 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 andor MUAC 125 and 115 cm This definition is also supported by USAID There are about 18 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 studysurveillance 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 cliniclab 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 EFER 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 EFER 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 EFER for developmental assessment
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None