Clinical trial NCT06305442: Microbiota Directed Food for Children With Moderate Acute Malnutrition
Official title: Efficacy of Microbiota-Directed Food in Children With Moderate Acute Malnutrition in Dhaka, Bangladesh
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Moderate Acute Malnutrition
Keywords: Microbiota Directed Food
Gut microbiota
MAM
Bangladesh
Lead sponsor: International Centre for Diarrhoeal Disease Research, Bangladesh
Sponsor class: OTHER
Collaborators: name: Washington University School of Medicine
First posted: 2024-03-12
Enrollment: 230
Sex: ALL
Minimum age (years): 6
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double blind, randomized, parallel group, clinical trial
Primary purpose: TREATMENT

Brief summary: Moderate acute malnutrition (MAM) refers to a condition characterized by a significant deficit in weight-for-length measurements in children aged 6 to 59 months. It is a crucial public health concern with detrimental effects on child growth, development, and overall well-being. Addressing MAM is crucial to prevent its progression to severe acute malnutrition (SAM) and to ensure healthy child development. To meet the nutritional requirement of MAM children, icddr,b have come up with a novel intervention named microbiota-directed food (MDF), a ready-to-use supplementary food. The investigator propose this efficacy trial to establish the evidence on the effect of this novel intervention on ponderal growth, microbial and proteomic recovery among the children with MAM in comparison to the standard RUSF.

Detailed description: Burden: Moderate acute malnutrition (MAM) refers to a condition characterized by a significant deficit in weight-for-length measurements in children aged 6 to 59 months. It is a crucial public health concern with detrimental effects on child growth, development, and overall well-being. Addressing MAM is crucial to prevent its progression to severe acute malnutrition (SAM) and to ensure healthy child development. MAM affects a significant number of children globally, particularly in low- and middle-income countries where malnutrition is prevalent. According to the 2022 Bangladesh Demographic and Health Survey (2022 BDHS), 24% of children under the age of 5 are stunted, while 11% are wasted. The prevalence of worldwide MAM children is higher than that of children with SAM and 31.3 million under 5 children (\~70%) was moderately wasted among all those children who were acutely malnourished in 2022. MAM children are found to be suffering from relative gut microbial immaturity, which is related to their growth faltering. Ready-to-use supplementary food (RUSF) is a key component of the outpatient treatment of MAM in community-based management. RUSF, being a ready-to-use food, does not require preparation or refrigeration and provides the necessary nutrients and energy for recovery from MAM.

Knowledge gap: Researchers at icddr,b in collaboration with Washington University in St. Louis, have developed a Microbiota-Directed Complementary Food (MDCF) formulation (based on locally available food ingredients) that has the potential to repair the gut microbiota of children with malnutrition. Results from a recently conducted study of MDCF on Bangladeshi children suffering from MAM showed that the children who received the food exhibited significantly faster rates of ponderal growth compared to those treated with a standard ready-to-use supplementary food (PR#18073). Early evidence, however, is limited to a small sample of children with MAM.

Relevance: To meet the nutritional requirement of MAM children, icddr,b have come up with a novel intervention named microbiota-directed food (MDF), a ready-to-use supplementary food by modifying the original MDCF recipe to meet the nutritional requirement of MAM children as well as to make it align with the existing WHO/UNICEF specifications for a nutritional intervention for treating acute malnutrition. The proposed formulation of MDF with adequate calorie content will improve the nutritional status by modulating and improving the gut microbial dysbiosis that is present in MAM children. Therefore, the investigator propose this efficacy trial to establish the evidence on the effect of this novel intervention on ponderal growth, microbial and proteomic recovery among the children with MAM in comparison to the standard RUSF.

Hypothesis (if any):

The locally developed MDF would be proven beneficial in nutritional recovery, repairing microbiota and restoring plasma biomarkers of healthy growth when compared to standard RUSF among children suffering from MAM.

Objectives:

Primary objectives:

•To assess the efficacy of MDF in improving the weight-for-length Z score (WLZ) of MAM children

Secondary:

* To investigate the efficacy of MDF in repairing the microbiota of MAM children
* To measure the efficacy of MDF in improving the Weight-for-Age Z-score (WAZ) in children with MAM
* To measure the efficacy of MDF in improving the Length-for-Age Z-score (LAZ) in children with MAM
* To explore and validate the impact of MDF supplement in restoring plasma and fecal biomarkers
* To monitor the change produced by MDF in rebalancing the body composition (fat mass % and fat-free mass %)
* To explore the efficacy of MDF in improving the cognitive, motor, and language function of MAM children

Methods:

Study Design: This study will be a double-blind, randomized controlled trial.

Participants: The trial will recruit 6-24-months-old children with Moderate Acute Malnutrition

Study Site: Bauniabadh and the adjacent slum area of Mirpur in Dhaka city.

Sample Size: 230; 2 arms; 115 per arm)

Intervention: Children in one arm will receive the MDF, and the children in the control arm will receive the conventional RUSF.

The children will receive intervention for 12 weeks with either the MDF or RUSF.

* 6-24-months children with MAM - 12 weeks intervention with MDF + 12 weeks follow up
* 6-24-months children with MAM - 12 weeks intervention with RUSF + 12 weeks follow up

Study Procedure Screening, and enrolment of study participants will be done in Bauniabadh and the adjacent slum area of Mirpur in Dhaka city. Initially 6-24-months-old children will be screened by the study health workers. Parents of eligible children who meet the inclusion criterion will be approached about enrolment into the study. A trained 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. After acquiring consent from the parents, at the beginning of the study, information will be sought on the demographic characteristics (families' wealth, standard of housing, family structure, home environment, parental characteristics etc.). Morbidity data will be collected weekly during the intervention period, and biweekly in the follow-up phase.

In this study, nutritional status will be assessed through anthropometry, comparing with WHO growth reference standards. BIA is a method of assessing body composition by measuring body fat in relation to lean body mass. It is an integral part of a health and nutrition assessment. BIA will be used to measure total fat and fat-free mass before and after treatment. This non-invasive test simply involves the placement of electrodes on the person's hand and foot. A low-level, imperceptible electrical current is sent through the body. The flow of the current is affected by the amount of water in the body. The device measures how this signal is impeded through different types of tissue as it passes through the body and provides estimates of body water from which body fat is calculated.

A food frequency questionnaire will be used to collect data on Infant and Young Child Feeding (IYCF) practices. Food frequency data will be evaluated using the Minimum Acceptable Diet indicator as it meets standards for both minimum dietary diversity and minimum meal frequency.

The Bayley Scales of Infant and Toddler Development (BSID-IV) will be used to assess the early childhood development (cognitive, motor, and language development) before and after the intervention. The Caregiver Reported Early Development Instruments (CREDI) long form, developed by Harvard University, will also be used in this study (21).

Blood samples will be collected before, after the intervention/treatment, and at the end of the follow-up period for measuring haemoglobin, serum protein (total protein and albumin), thiamine, zinc, vitamin B12, vitamin D, and folate levels.

Non-diarrheal stool samples will be collected at enrolment, then monthly during the intervention and follow-up phase from all the participants for measuring biomarkers of gut inflammation and assessment of the composition of gut microbiota and features of the microbiome.

Oral swab samples will be collected by using commercial kit from each child at enrolment, after the intervention/treatment, and at the end of the follow-up period for measuring microbiota.

Eligibility criteria: Inclusion Criteria:

1. Parent(s) willing to sign consent form
2. Children aged 6-24 months
3. WLZ score \<-2 to ≥-3 and/or MUAC ≥115 mm to \<125 mm without bilateral pedal edema at the time of randomization

Exclusion Criteria:

1. Medical conditions: Malnourished children with complications requiring acute phase treatment in a hospital, children with tuberculosis or any chronic illness(es).
2. Any congenital/acquired disorder affecting growth, i.e., known case of trisomy-21 or cerebral palsy; children on an exclusion diet for the treatment of persistent diarrhea; having known history of soy, peanut or milk protein allergy
3. Severe anaemia (\< 8 gm/dl)
4. Antibiotic use (within last 7 days before the onset of intervention)
5. Receiving concurrent treatment for another condition
6. children participating in other food intervention program

Primary outcomes:
measure: Mean change in Weight-for-Length Z-score (WLZ)
timeFrame: Baseline to 12 weeks of intervention followed by 12 weeks of follow-up
Secondary outcomes:
measure: Microbial community repair
timeFrame: Baseline to 12 weeks of intervention followed by 12 weeks of follow-up
measure: Validated plasma and faecal biomarkers of health status (prioritized Luminex/ELISA panel including mediators of growth, systemic inflammation, gut inflammation/entero-pathogen burden)
timeFrame: Baseline to 12 weeks of intervention followed by 12 weeks of follow-up
measure: Mean change in Weight-for-Age Z-score (WAZ)
timeFrame: Baseline to 12 weeks of intervention followed by 12 weeks of follow-up
measure: Mean change in Length-for-Age Z-score (LAZ)
timeFrame: Baseline to 12 weeks of intervention followed by 12 weeks of follow-up
measure: Mean change in body composition (% body fat mass and % fat-free mass)
timeFrame: Baseline to 12 weeks of intervention
measure: Bayley Scales of early childhood development (cognitive, motor, language development)
timeFrame: Baseline to 12 weeks of intervention
Other outcomes:
Locations:
city: Dhaka
country: Bangladesh
facility: Mirpur Study site
Study officials:
affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh
name: Ishita Mostafa, BDS, MPH
role: PRINCIPAL_INVESTIGATOR
References: