Modified Dosage for Severe Acute Malnutrition

Study Overview
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Brief Summary
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Protocols for the community-based management of acute malnutrition (CMAM) have not changed significantly for more than 20 years, with relatively complex treatment protocols and persistent supply chain challenges that have limited overall program coverage, leaving millions of malnourished children without care annually. The overarching goal of this research project is to simultaneously test two novel simplified approaches in CMAM with potential to improve program coverage. The simplified approach includes two parallel clinical trials for SAM and MAM treatment. Two fixed-dose regimes of RUTF will be tested against the current weight-based dosing of RUTF for children with SAM.

Official Title
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Safety Efficacy, and Cost-effectiveness of Modified Doses of Ready-to-use Therapeutic Food for the Treatment of Severe Acute Malnutrition Among Children 6-59 Months of Age in Ethiopia

Conditions
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Severe Acute Malnutrition

Intervention / Treatment
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* Dietary Supplement: ready-to-use therapeutic food (RUTF)
* Drug: Amoxicillin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 6-59 months Reside in the catchment area of the health post where the trial is to be conducted without plans to leave the area over the next year Uncomplicated severe acute malnutrition, as defined by no signs of severe illness that would require referral to inpatient facility Pass appetite test conducted at the time of enrollment Consent for randomization into the study given by mother, father, and/or other primary caregiver Mid-upper arm circumference less than 115 mm and/or nutritional edema Weight-for-height Z-score (WHZ) less than -3 (will not count towards planned sample size) Exclusion Criteria: Complicated acute malnutrition with severe illness requiring transfer to a stabilization center or hospital for treatment. This includes, but is not limited to: a. Hypothermia b. High fever c. Signs of hypoglycemia d. Lethargy or altered mental status e. Moderate to severe dehydration f. Shock g. Other medical complications requiring hospitalization or higher-level medical evaluation Treatment for acute malnutrition, either as an inpatient or outpatient, within the past 3 months Known chronic medical illness such as severe cerebral palsy, severe congenital anomalies such as unrepaired congenital heart disease, Down syndrome, hydrocephalus, unrepaired cleft lip or palate, or other conditions that would be expected to contribute to difficulty feeding the prescribed amounts of therapeutic or supplementary food

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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control Group<br>Standard weight-based dosing of Ready-to-Use Therapeutic Food (RUTF) at a dose of 150-200 kcal/kg/day | Dietary Supplement: ready-to-use therapeutic food (RUTF)<br>* Standard formulation meeting UNICEF specifications: https://www.unicef.org/supply/sites/unicef.org.supply/files/2023-04/U239977-RUTF-Novel-Specification.pdf<br>Drug: Amoxicillin<br>* Standard weight-based dosing per Ehtiopian national guidelines<br>|
| Experimental: SAM Experimental A<br>2 sachets (1000 kcal) of RUTF per day | Dietary Supplement: ready-to-use therapeutic food (RUTF)<br>* Standard formulation meeting UNICEF specifications: https://www.unicef.org/supply/sites/unicef.org.supply/files/2023-04/U239977-RUTF-Novel-Specification.pdf<br>Drug: Amoxicillin<br>* Standard weight-based dosing per Ehtiopian national guidelines<br>|
| Experimental: SAM Experimental B<br>2 sachets (1000 kcal) per day while MUAC < 115mm and/or edema and/or WHZ < -3; then decreasing to 1 sachet (500 kcal) per day while MUAC 115-124 and WHZ -2 to -3 and no edema | Dietary Supplement: ready-to-use therapeutic food (RUTF)<br>* Standard formulation meeting UNICEF specifications: https://www.unicef.org/supply/sites/unicef.org.supply/files/2023-04/U239977-RUTF-Novel-Specification.pdf<br>Drug: Amoxicillin<br>* Standard weight-based dosing per Ehtiopian national guidelines<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| short-term nutritional recovery from severe acute malnutrition (SAM) | two consecutive weeks with MUAC > 12.4 cm and/or WHZ >= -2 and/or resolution of edema, depending on enrollment criteria | up to 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| weight gain during treatment |  | weekly for up to 16 weeks | 
| MUAC gain during treatment |  | weekly for up to 16 weeks | 
| length/height gain during treatment |  | weekly for up to 16 weeks | 
| changes to phase angle (PhA) as measured by bioelectrical impedance analysis |  | up to weekly for up to 16 weeks | 
| changes to extracellular water (ECW) as measured by bioelectrical impedance analysis |  | up to weekly for up to 16 weeks | 
| changes to total body water (TBW) as measured by bioelectrical impedance analysis |  | up to weekly for up to 16 weeks | 
| changes to fat free mass as measured by bioelectrical impedance analysis |  | up to weekly for up to 16 weeks | 
| changes in immunological function during treatment as measured by quantification of T-cell recombination excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs) on dried blood spots |  | up to weekly for up to 16 weeks | 
| rates of acute illness, including diarrhea, vomiting, and fever during treatment |  | weekly for up to 16 weeks | 
| mortality |  | up to 16 weeks | 
| hospitalization |  | up to 16 weeks | 
| duration of treatment required prior to short-term recovery |  | up to 16 weeks | 
| medium-term vital status | calculated as number of children who die divided by total number of children initially enrolled | up to 6 months post-recovery | 
| medium-term nutritional status | calculated as number of children who develop acute malnutrition by the total number of children initially enrolled | up to 6 months post-recovery | 
| medium-term rates of relapse to SAM |  | up to 6 months post-recovery | 
| medium-term rates of relapse to MAM |  | up to 6 months post-recovery | 
| medium-term rates of hospitalization |  | up to 6 months post-recovery | 
| medium-term weight gain |  | up to 6 months post-recovery | 
| medium-term MUAC gain |  | up to 6 months post-recovery | 
| medium-term length/height gain |  | 6 months post-recovery | 
| medium-term phase angle (PhA) as measured by bioelectrical impedance analysis |  | 6 months post-recovery | 
| medium-term extracellular water (ECW) as measured by bioelectrical impedance analysis |  | 6 months post-recovery | 
| medium-term total body water (TBW) as measured by bioelectrical impedance analysis |  | 6 months post-recovery | 
| medium-term fat free mass as measured by bioelectrical impedance analysis |  | 6 months post-recovery | 
| medium-term immunological function during treatment as measured by quantification of T-cell recombination excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs) on dried blood spots |  | 6 months post-recovery | 
| short-term cost-efficiency | calculated as the total costs of the treatment for all children divided by the number of children who achieve nutritional recovery | up to 16 weeks | 
| medium-term cost-efficiency | calculated as the total costs of the treatment for all children divided by the number of children who sustain nutritional recovery | 6 months post-recovery |