Rice Bran-based Supplemental Foods for the Treatment of Childhood Malnutrition

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy of treating children with severe acute malnutrition (SAM) with a locally produced ready-to-use therapeutic food (RUTF) with or without rice bran.

Detailed Description
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Rice bran is a nutrient dense food ingredient with prebiotics and phytochemicals, as well as vitamins, fatty acids, and amino acids. The investigators will determine if the inclusion of rice bran to locally produced RUTFs will improve SAM treatment for children in Indonesia. This will be assessed by standard anthropometric measures and determining the modulation of the malnourished child's gut microbiome and metabolome. The study will also assess rates of relapse in the entire cohort. This study will yield new information of direct importance and impact to public health nutrition and advance our knowledge and treatment of SAM in Indonesia. Investigation of the gut-microbiota metabolism following consumption of rice bran provided in RUTFs compared to RUTF without rice bran included will provide key mechanistic insights for repairing nutrient absorptive functions in the gut, sustaining gut health in treated children and inform long-term treatment solutions for SAM.

Official Title
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Rice Bran in Ready-to-use Therapeutic Foods for Microbiota-targeted Treatment of Childhood Malnutrition

Conditions
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Severe Acute Malnutrition

Intervention / Treatment
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* Dietary Supplement: Ready-to-use therapeutic food with heat stabilized rice bran
* Dietary Supplement: Ready-to-use therapeutic food (no rice bran)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing to participate in the study, with parent(s) signing the informed consent. If the caretaker denies the participation of the child, the child will be enrolled for treatment through the health system, but the information will be not considered for the purpose of the trial. Child identified with a weight-for-height z-score WHZ of < -2.5 (SAM children and children with advanced moderate acute malnutrition) and/or mid-upper arm circumference (MUAC) <115 mm) or a child with mild to moderate nutritional edema (regardless of anthropometry). Being qualified for outpatient treatment. Aged 6-59 months old upon enrolment Pass appetite test (taste test) (as stipulated by WHO guidelines on the treatment of SAM). See appetite test document attached. Not having consumed RUTF in the last two months Exclusion Criteria: Children detected with severe acute malnutrition younger than 6 months of age will be excluded from the project, as well as any child with a body weight <4.0 kg. Children 6-59 months old who, when diagnosed with SAM, have been detected with medical complications, with TB, HIV positive status, one or more signs from the Integrated Management of Childhood Illness (IMCI) guidelines, severe oedema (+++) or who have failed the appetite test (see appetite test document attached). Medical complications include: Cough/difficulty in breathing; Diarrhea; Fever; Ear Problems. IMCI signs will be identified according to WHO definition and include not able to drink or breastfeed; vomiting; convulsions; lethargy. Participating in another clinical trial Any congenital disorder that interferes with normal nutrient intake; chronic conditions including but not exclusively disorders of heart, kidney or liver (children to be screened by a physician). SAM with complications requiring hospital treatment. (Upon discharge from hospital, the child will be re-evaluated for inclusion in the study). Siblings will not be allowed to participate in the trial Withdrawal criteria: Not consuming the RUTF supplementation at all in >4 days a week in 2 consecutive weeks. Not providing samples or completing forms/questionnaires at study visits Developing medical complications requiring hospitalization Not gaining weight after 1 month of treatment Major reactions to intervention

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 59 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Control study arm: Locally produced Ready to use therapeutic food (RUTF) Intervention study arm: Locally produced Ready to use therapeutic food plus rice bran (RUTF+RB)
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ready-to-use therapeutic food, no rice bran (control/comparator)<br>Randomized participants will receive a locally produced ready-to-use therapeutic food to be consumed daily. | Dietary Supplement: Ready-to-use therapeutic food (no rice bran)<br>* Children assigned to the active comparator group will be treated for severe acute malnutrition with a novel ready-to-use therapeutic food (no rice bran).<br>|
| Experimental: Ready-to-use therapeutic food, with heat stabilized rice bran (Experimental)<br>Randomized participants will receive a locally produced ready-to-use therapeutic food with 5% heat stabilized rice bran to be consumed daily. | Dietary Supplement: Ready-to-use therapeutic food with heat stabilized rice bran<br>* Children assigned to the experimental group will be treated for severe acute malnutrition with a novel ready-to-use therapeutic food that contains 5% heat stabilized rice bran.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of the locally produced ready-to-use therapeutic food + heat stabilized rice bran as compared to locally produced ready-to-use therapeutic food alone in the treatment of severe acute malnutrition as determined by child weight. | This will be assessed by measures of: - Weight | Baseline, week 4, week 8, and week 16 | 
| Efficacy of the locally produced ready-to-use therapeutic food + heat stabilized rice bran as compared to locally produced ready-to-use therapeutic food alone in the treatment of severe acute malnutrition as determined by mid-upper arm circumference. | This will be assessed by measures of: -Mid-upper arm circumference | Changes between baseline, week 4, week 8, and week 16 | 
| Efficacy of the locally produced ready-to-use therapeutic food + heat stabilized rice bran as compared to locally produced ready-to-use therapeutic food alone in the treatment of severe acute malnutrition as determined by morbidity. | This will be assessed by measures of: - Morbidity (diarrhea, fever, vomiting, upper or lower respiratory infection) | Changes between baseline, week 4, week 8, and week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stool microbiota composition | Determine stool microbiota composition of infants in both arms over time using 16S rRNA sequencing and shotgun metagenomic sequencing. | Changes between baseline, week 4, week 8, and week 16 | 
| Dried blood spot metabolite profile | Dried blood spots will be analyzed for metabolites. | Changes between baseline, week 4, week 8, and week 16 | 
| Relapse | Determine the number of participants that experience severe acute malnutrition relapse 4 weeks after the treatment/intervention has ended. | Week 16 (end of study) | 
| Percent of children recovered | The number of children recovered in the 4 week treatment period will be determined as well as the time to recovery (days). | Baseline, week 4, week 8, and week 16 |