Executive Function DisorderNCT05629624
Evaluation of Executive Function and Emotional Regulation in Children in Bangladesh
A study testing Chickpea based RUSF, E-RUSF and Outcome reference group/RUSF in people with Executive Function Disorder and Emotional Regulation, run by Boston Children's Hospital at 1 site in Bangladesh.
Trial 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 EF/ER outcomes at three years of age. Read more about this study
- Who is it for?
- Ages 12 to 39 monthsHealthy volunteers can take part
- Conditions the study is for
- Executive Function Disorder, Emotional Regulation, Malnutrition, Child
- What is being tested?
- Chickpea based RUSF, E-RUSF and Outcome reference group/RUSF
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 297 participants
- Where
- 1 siteBangladesh
- Study dates
- 7 Feb 2022to 31 Jan 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 39 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Inclusion criteria for malnourished (MAM) children at 1 and 3 years of age: All of the following criteria must be met for a subject to be eligible to participate in the study
- Mother willing to sign consent form
- 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.
Show all 17Show fewer
- 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.
- Inclusion criteria for Control group with normal health (normal Z score):
- 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.
Who cannot join
- Exclusion criteria for malnourished (MAM) children: Meeting any of the following criteria will exclude a subject from study participation
- Mother who is not willing to sign a consent form.
- 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.
- Exclusion criteria for Control group with normal health (normal Z score): Meeting any of the following criteria will exclude a subject from study participation -
Show all 11Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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 EF/ER 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.
Read the 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 14.6% 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 5.5 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 (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.
- Being tested
- Chickpea based RUSF, E-RUSF, Outcome reference group/RUSF
- Keywords
- Executive Function, Emotional Regulation, Malnutrition, Children, Bangladesh
- Medical subject headings
- Emotional Regulation, Child Nutrition Disorders, Malnutrition
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Chickpea based RUSFDietary supplement
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-RUSFDietary supplement
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/RUSFDietary supplement
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.
| Study group | Role | What they receive |
|---|---|---|
| Chickpea based RUSF | Experimental | 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. Receives: Dietary Supplement: Chickpea based RUSF |
| E-RUSF | Experimental | 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. Receives: Dietary Supplement: E-RUSF |
| Well-nourished children | No intervention | Well-nourished children at 1 year of age (WLZ/WHZ score >-1 SD). No nutritional or psychosocial intervention. Only follow-up. |
| Outcome reference group | Experimental | 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. Receives: Dietary Supplement: Outcome reference group/RUSF |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in BAYLEY-4 scores from 1 year to 2 years of age
Bayley-4 Scales of Infant and Toddler Development is standardized developmental assessment tool for determining a child's developmental status at a given age (up to 42 months) BAYLEY-4 assess development in children of 1-42 months old in 5 domains: cognition, motor, language, socio-emotional, and adaptive behavior.
Measured: All enrolled children at 1 year ±1m(11m-13m) and 2 years ±1m(23m-25m)
Secondary outcomes (10)
Change in functional Near Infrared spectroscopy (fNIRS) from 1 year to 2 years of age
Brain activity will be assessed using fNIRS, a method that measures changes in blood oxygen concentration as a consequence of neural activity in the brain. fNIRS can be used to measure brain activity that is related to an externally presented stimulus, or it can measure the connections between brain activity in different parts of the brain with no explicit external stimulus presentation. Measures of hemodynamics reported by fNIRS include relative concentration changes in oxy-hemoglobin, deoxy-hemoglobin and total hemoglobin. The fNIRS measurement is completely non-invasive and has been used in infant studies of brain activity for over 15 years.
Measured: All enrolled children at 1 year ±1m(11m-13m) and 2 years ±1m(23m-25m)
Change in Electroencephalogram (EEG) power from 1 year to 2 years of age
The EEG will be used to investigate functional connectivity and power spectra across different scalp regions during both rest (baseline) and task activity. In addition, we will deploy a number of perceptual and cognitive tasks while recording the event-related potential (a subset of the EEG). . ERPs measure changes in electrical activity of the brain in response to stimulus presentation (auditory, visual, etc0. In addition, sophisticated signal processing/machine learning approaches can be applied to examine EEG frequency information (e.g., theta activity, phase amplitude coupling), which could serve as indices of local circuit connectivity. The EEG works by detecting small charges emitted by the brain during activity, amplifying the signals, and graphing signals in real time.
Measured: All enrolled children at 1 year ±1m(11m-13m) and 2 years ±1m(23m-25m)
Change in LENA (Language Environment Analysis) from 1 year to 2 years of age
The LENA recorder and software measure the frequency of vocalization/verbalizations and conversational turns in children. Digital audio recordings are collected in a participant's home at baseline visit and annually afterwards. Thus, we will be able to see the influence of language input at different crucial points in early development. Recording data at multiple time points also gives us a measure of the consistency of the language environment.
Measured: Baseline at 1 year ±1m(11m-13m) for control and intervention and 3 years ±2m(34m-38m) for the outcome reference group, and during follow up of control and intervention group at 2 years ±1m(23m-25m) and 3 years ±2m(34m-38m) of age.
Change in Parent-Child Interaction coded data from 1 year to 2 years of age
A 10-15 minute interaction between parent and child will be recorded. Parents will be asked to engage their child in play or conversations in the presence and absence of toys and books. The child will also play with the toys/books while the parent completes short surveys or watches a short video. The interaction will be filmed and transcribed. Language transcripts and videos will be coded for the child's and parent's use of language and mutual engagement.
Measured: All enrolled children at 1 year ±1m(11m-13m) and 2 years ±1m(23m-25m)
Change in weight in kilograms at the start of intervention until they reach within 1 standard deviation of the mean
Weight will be measured at enrollment, then weekly during rehabilitation to achieve anthropometric recovery, and then quarterly for the duration of the study (till 36months of age) from 140 children who have enrolled with MAM. Weight data will also be collected from 70 normal children at enrolment, then monthly for 3 months, then quarterly for the duration of the study (until 36months of age).
Measured: Baseline, weekly, quarterly
Change in height in meters at the start of intervention until they reach within 1 standard deviation of the mean
Height will be measured at enrollment, then weekly during rehabilitation to achieve anthropometric recovery, and then quarterly for the duration of the study (till 36months of age) from 140 children who have enrolled with MAM. Height data will also be collected from 70 normal children at enrolment, then monthly for 3 months, then quarterly for the duration of the study (until 36 months of age).
Measured: Baseline, weekly, quarterly
Change in Mid-upper arm circumference (MUAC) in centimeters at the start of intervention until they reach within 1 standard deviation of the mean
MUAC will be measured at enrollment, then weekly during rehabilitation to achieve anthropometric recovery, and then quarterly for the duration of the study (till 36months of age) from 140 children who have enrolled with MAM. MUAC data will also be collected from 70 normal children at enrolment, then monthly for 3 months, then quarterly for the duration of the study (until 36months of age).
Measured: Baseline, weekly, quarterly
Change in head circumference in centimeters
Head circumference will be measured at enrollment, at the age of 2 years and 3 years.
Measured: Baseline, 2 years, 3 years
Change in blood analytes
2-3 ml of child blood will be collected at enrollment, at the time of achieved ideal wt/ht (anthropometry recovery) or at the end of 3 months of E-RUSF/RUSF intervention, 24 months and 36 months of age to perform concentration of 24 vitamins and mineral micro nutrients, functional lipid concentrations in red cell membrane, serum siallylated milk oligo saccharides, Lutein/ zeaxantnine / cryptoxanthine and Microbiome directed blood metabolome.
Measured: Baseline, 3 months, 24 months, 36 months
Change in stool metabolome
Stool sample will be collected at enrollment, at the time of achieved ideal wt/ht (anthropometry recovery), or at the end of 3 months of E-RUSF/RUSF intervention, 24 months and 36 months of age to perform 16S microbial sequencing, Functional pathway analysis and stool metabolome.
Measured: Baseline, 3 months, 24 months, 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2022
- Study start7 Feb 2022
- Primary completion31 Jan 2025
- Study completion31 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (37)Papers the sponsor has linked to this study.
- Other trials for Executive Function DisorderStudies of the same condition, open and under way.
- More trials run by Boston Children's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- We will recruit a sample of malnourished children and randomly assign to different intervention arms. We will also have a control sample of well-nourished children for comparison analysis.
- Masking
- None (open label)
- Enrolment
- 297 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- The University of The West Indies, International Centre for Diarrhoeal Disease Research, Bangladesh, University of Auckland, New Zealand, Wellcome Trust
- Responsible party
- Principal investigator, Charles Alexander Nelson III, Boston Children's Hospital
- Investigators
- Charles Nelson, Ph.D, Principal investigator, Children's Hospital Boston/Harvard UniversityTerrence Forrester, Dr, Principal investigator, University of the West Indies
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05629624
- Sponsor's protocol ID
- M4EFaD/Dhaka PR-21084
- Status last verified
- Jun 2026
- First submitted
- 4 Oct 2022
- Last updated
- 29 Jun 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Participants will sign a form, to give us permission to release participant data information to authorized researchers and the safety committees, icddr,b Ethical Review Committee, regulatory authorities (both in Bangladesh and the United States), the study sponsor, Synapse (a research data sharing and collaboration platform) designees, and other research organizations.
Publications
Bhutta ZA, Berkley JA, Bandsma RHJ, Kerac M, Trehan I, Briend A. Severe childhood malnutrition. Nat Rev Dis Primers. 2017 Sep 21;3:17067. doi: 10.1038/nrdp.2017.67.
PubMed 28933421Black RE, Allen LH, Bhutta ZA, Caulfield LE, de Onis M, Ezzati M, Mathers C, Rivera J; Maternal and Child Undernutrition Study Group. Maternal and child undernutrition: global and regional exposures and health consequences. Lancet. 2008 Jan 19;371(9608):243-60. doi: 10.1016/S0140-6736(07)61690-0. No abstract available.
PubMed 18207566Collins S, Dent N, Binns P, Bahwere P, Sadler K, Hallam A. Management of severe acute malnutrition in children. Lancet. 2006 Dec 2;368(9551):1992-2000. doi: 10.1016/S0140-6736(06)69443-9.
PubMed 17141707Prado EL, Dewey KG. Nutrition and brain development in early life. Nutr Rev. 2014 Apr;72(4):267-84. doi: 10.1111/nure.12102. Epub 2014 Mar 28.
PubMed 24684384Mora JO, Herrera MG, Sellers SG, Ortiz N. Nutrition, social environment and cognitive performance of disadvantaged Colombian children at three years (1). Prog Clin Biol Res. 1981;77:403-20. No abstract available.
PubMed 7335695Super CM, Herrera MG, Mora JO. Long-term effects of food supplementation and psychosocial intervention on the physical growth of Colombian infants at risk of malnutrition. Child Dev. 1990 Feb;61(1):29-49.
PubMed 2307045Adair LS, Pollitt E. Outcome of maternal nutritional supplementation: a comprehensive review of the Bacon Chow study. Am J Clin Nutr. 1985 May;41(5):948-78. doi: 10.1093/ajcn/41.5.948.
PubMed 3993612McKay H, Sinisterra L, McKay A, Gomez H, Lloreda P. Improving cognitive ability in chronically deprived children. Science. 1978 Apr 21;200(4339):270-8. doi: 10.1126/science.635585.
PubMed 635585Blanton LV, Charbonneau MR, Salih T, Barratt MJ, Venkatesh S, Ilkaveya O, Subramanian S, Manary MJ, Trehan I, Jorgensen JM, Fan YM, Henrissat B, Leyn SA, Rodionov DA, Osterman AL, Maleta KM, Newgard CB, Ashorn P, Dewey KG, Gordon JI. Gut bacteria that prevent growth impairments transmitted by microbiota from malnourished children. Science. 2016 Feb 19;351(6275):10.1126/science.aad3311 aad3311. doi: 10.1126/science.aad3311.
PubMed 26912898Cerdo T, Dieguez E, Campoy C. Early nutrition and gut microbiome: interrelationship between bacterial metabolism, immune system, brain structure, and neurodevelopment. Am J Physiol Endocrinol Metab. 2019 Oct 1;317(4):E617-E630. doi: 10.1152/ajpendo.00188.2019. Epub 2019 Jul 30.
PubMed 31361544Gunston GD, Burkimsher D, Malan H, Sive AA. Reversible cerebral shrinkage in kwashiorkor: an MRI study. Arch Dis Child. 1992 Aug;67(8):1030-2. doi: 10.1136/adc.67.8.1030.
PubMed 1520007Gordon JI, Dewey KG, Mills DA, Medzhitov RM. The human gut microbiota and undernutrition. Sci Transl Med. 2012 Jun 6;4(137):137ps12. doi: 10.1126/scitranslmed.3004347.
PubMed 22674549Million M, Diallo A, Raoult D. Gut microbiota and malnutrition. Microb Pathog. 2017 May;106:127-138. doi: 10.1016/j.micpath.2016.02.003. Epub 2016 Feb 4.
PubMed 26853753Fox SE, Levitt P, Nelson CA 3rd. How the timing and quality of early experiences influence the development of brain architecture. Child Dev. 2010 Jan-Feb;81(1):28-40. doi: 10.1111/j.1467-8624.2009.01380.x.
PubMed 20331653Charbonneau MR, O'Donnell D, Blanton LV, Totten SM, Davis JC, Barratt MJ, Cheng J, Guruge J, Talcott M, Bain JR, Muehlbauer MJ, Ilkayeva O, Wu C, Struckmeyer T, Barile D, Mangani C, Jorgensen J, Fan YM, Maleta K, Dewey KG, Ashorn P, Newgard CB, Lebrilla C, Mills DA, Gordon JI. Sialylated Milk Oligosaccharides Promote Microbiota-Dependent Growth in Models of Infant Undernutrition. Cell. 2016 Feb 25;164(5):859-71. doi: 10.1016/j.cell.2016.01.024. Epub 2016 Feb 18.
PubMed 26898329
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05629624
- Acronym / sponsor ID
- M4EFaD/Dhaka PR-21084
- Keywords
- Executive Function, Emotional Regulation, Malnutrition, Children, Bangladesh
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 297 participants (actual)
- Lead sponsor
- Boston Children's HospitalUniversity, hospital or other
- Collaborators
- The University of The West Indies, International Centre for Diarrhoeal Disease Research, Bangladesh, University of Auckland, New Zealand, Wellcome Trust
- Study start
- 7 Feb 2022 (actual)
- Primary completion
- 31 Jan 2025 (actual)
- Study completion
- 31 Jan 2025 (actual)
- First posted
- 29 Nov 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 EF/ER 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 14.6% 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 5.5 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 (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.
Study design
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- We will recruit a sample of malnourished children and randomly assign to different intervention arms. We will also have a control sample of well-nourished children for comparison analysis.
| Arm | Type | Receives |
|---|---|---|
| Chickpea based RUSF | Experimental | Dietary Supplement: Chickpea based RUSFLocally 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. |
| E-RUSF | Experimental | Dietary Supplement: E-RUSFEnhanced 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. |
| Well-nourished children | No intervention | –Well-nourished children at 1 year of age (WLZ/WHZ score >-1 SD). No nutritional or psychosocial intervention. Only follow-up. |
| Outcome reference group | Experimental | Dietary Supplement: Outcome reference group/RUSF3 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. |
Who may qualify
- Ages
- 12 to 39 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (17 listed)
- Inclusion criteria for malnourished (MAM) children at 1 and 3 years of age: All of the following criteria must be met for a subject to be eligible to participate in the study
- Mother willing to sign consent form
- 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.
Key exclusion criteria (11 listed)
- Exclusion criteria for malnourished (MAM) children: Meeting any of the following criteria will exclude a subject from study participation
- Mother who is not willing to sign a consent form.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Chickpea based RUSFOne 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. | Dietary supplement | Chickpea based RUSF |
| E-RUSFThe 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. | Dietary supplement | E-RUSF |
| Outcome reference group/RUSFWe 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. | Dietary supplement | Outcome reference group |
Primary outcome
Change in BAYLEY-4 scores from 1 year to 2 years of age
Time frame: All enrolled children at 1 year ±1m(11m-13m) and 2 years ±1m(23m-25m)
Bayley-4 Scales of Infant and Toddler Development is standardized developmental assessment tool for determining a child's developmental status at a given age (up to 42 months) BAYLEY-4 assess development in children of 1-42 months old in 5 domains: cognition, motor, language, socio-emotional, and adaptive behavior.
10 secondary outcomes
Change in functional Near Infrared spectroscopy (fNIRS) from 1 year to 2 years of age
Time frame: All enrolled children at 1 year ±1m(11m-13m) and 2 years ±1m(23m-25m)
Change in Electroencephalogram (EEG) power from 1 year to 2 years of age
Time frame: All enrolled children at 1 year ±1m(11m-13m) and 2 years ±1m(23m-25m)
Change in LENA (Language Environment Analysis) from 1 year to 2 years of age
Time frame: Baseline at 1 year ±1m(11m-13m) for control and intervention and 3 years ±2m(34m-38m) for the outcome reference group, and during follow up of control and intervention group at 2 years ±1m(23m-25m) and 3 years ±2m(34m-38m) of age.
Change in Parent-Child Interaction coded data from 1 year to 2 years of age
Time frame: All enrolled children at 1 year ±1m(11m-13m) and 2 years ±1m(23m-25m)
Change in weight in kilograms at the start of intervention until they reach within 1 standard deviation of the mean
Time frame: Baseline, weekly, quarterly
Change in height in meters at the start of intervention until they reach within 1 standard deviation of the mean
Time frame: Baseline, weekly, quarterly
Change in Mid-upper arm circumference (MUAC) in centimeters at the start of intervention until they reach within 1 standard deviation of the mean
Time frame: Baseline, weekly, quarterly
Change in head circumference in centimeters
Time frame: Baseline, 2 years, 3 years
Change in blood analytes
Time frame: Baseline, 3 months, 24 months, 36 months
Change in stool metabolome
Time frame: Baseline, 3 months, 24 months, 36 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2026.
- Background: PubMed 28933421Bhutta ZA, Berkley JA, Bandsma RHJ, Kerac M, Trehan I, Briend A. Severe childhood malnutrition. Nat Rev Dis Primers. 2017 Sep 21;3:17067. doi: 10.1038/nrdp.2017.67.
- Background: PubMed 18207566Black RE, Allen LH, Bhutta ZA, Caulfield LE, de Onis M, Ezzati M, Mathers C, Rivera J; Maternal and Child Undernutrition Study Group. Maternal and child undernutrition: global and regional exposures and health consequences. Lancet. 2008 Jan 19;371(9608):243-60. doi: 10.1016/S0140-6736(07)61690-0. No abstract available.
- Background: PubMed 17141707Collins S, Dent N, Binns P, Bahwere P, Sadler K, Hallam A. Management of severe acute malnutrition in children. Lancet. 2006 Dec 2;368(9551):1992-2000. doi: 10.1016/S0140-6736(06)69443-9.
- Background: PubMed 24684384Prado EL, Dewey KG. Nutrition and brain development in early life. Nutr Rev. 2014 Apr;72(4):267-84. doi: 10.1111/nure.12102. Epub 2014 Mar 28.
- Background: PubMed 7335695Mora JO, Herrera MG, Sellers SG, Ortiz N. Nutrition, social environment and cognitive performance of disadvantaged Colombian children at three years (1). Prog Clin Biol Res. 1981;77:403-20. No abstract available.
- Background: PubMed 2307045Super CM, Herrera MG, Mora JO. Long-term effects of food supplementation and psychosocial intervention on the physical growth of Colombian infants at risk of malnutrition. Child Dev. 1990 Feb;61(1):29-49.
- Background: PubMed 3993612Adair LS, Pollitt E. Outcome of maternal nutritional supplementation: a comprehensive review of the Bacon Chow study. Am J Clin Nutr. 1985 May;41(5):948-78. doi: 10.1093/ajcn/41.5.948.
- Background: PubMed 635585McKay H, Sinisterra L, McKay A, Gomez H, Lloreda P. Improving cognitive ability in chronically deprived children. Science. 1978 Apr 21;200(4339):270-8. doi: 10.1126/science.635585.
- Background: PubMed 26912898Blanton LV, Charbonneau MR, Salih T, Barratt MJ, Venkatesh S, Ilkaveya O, Subramanian S, Manary MJ, Trehan I, Jorgensen JM, Fan YM, Henrissat B, Leyn SA, Rodionov DA, Osterman AL, Maleta KM, Newgard CB, Ashorn P, Dewey KG, Gordon JI. Gut bacteria that prevent growth impairments transmitted by microbiota from malnourished children. Science. 2016 Feb 19;351(6275):10.1126/science.aad3311 aad3311. doi: 10.1126/science.aad3311.
- Background: PubMed 31361544Cerdo T, Dieguez E, Campoy C. Early nutrition and gut microbiome: interrelationship between bacterial metabolism, immune system, brain structure, and neurodevelopment. Am J Physiol Endocrinol Metab. 2019 Oct 1;317(4):E617-E630. doi: 10.1152/ajpendo.00188.2019. Epub 2019 Jul 30.
- Background: PubMed 1520007Gunston GD, Burkimsher D, Malan H, Sive AA. Reversible cerebral shrinkage in kwashiorkor: an MRI study. Arch Dis Child. 1992 Aug;67(8):1030-2. doi: 10.1136/adc.67.8.1030.
- Background: PubMed 22674549Gordon JI, Dewey KG, Mills DA, Medzhitov RM. The human gut microbiota and undernutrition. Sci Transl Med. 2012 Jun 6;4(137):137ps12. doi: 10.1126/scitranslmed.3004347.
- Individual participant dataSharing planned: Yes. Participants will sign a form, to give us permission to release participant data information to authorized researchers and the safety committees, icddr,b Ethical Review Committee, regulatory authorities (both in Bangladesh and the United States), the study sponsor, Synapse (a research data sharing and collaboration platform) designees, and other research organizations.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Charles Nelson, Ph.D principal investigator
Children's Hospital Boston/Harvard University
Terrence Forrester, Dr principal investigator
University of the West Indies
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Chickpea based RUSF, E-RUSF and Outcome reference group/RUSF in people with Executive Function Disorder and Emotional Regulation, run by Boston Children's Hospital at 1 site in Bangladesh.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Bangladesh. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in BAYLEY-4 scores from 1 year to 2 years of age (time frame: All enrolled children at 1 year ±1m(11m-13m) and 2 years ±1m(23m-25m)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05629624, which also lists 37 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2026.