Modified Dosage for Severe Acute Malnutrition (MODAM-SAM)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Severe Acute Malnutrition
• Intervention / Treatment: Drug: Amoxicillin; Dietary supplement: ready-to-use therapeutic food (RUTF)

• Study Type: Interventional
• Enrollment (Estimated): 2400
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Indi Trehan, MD MPH DTM&H; Phone Number: +12067696068; Email: itrehan@uw.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 6-59 months
2. 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
3. Uncomplicated severe acute malnutrition, as defined by no signs of severe illness that would require referral to inpatient facility
4. Pass appetite test conducted at the time of enrollment
5. Consent for randomization into the study given by mother, father, and/or other primary caregiver
6. Mid-upper arm circumference less than 115 mm and/or nutritional edema
7. Weight-for-height Z-score (WHZ) less than -3 (will not count towards planned sample size)

Exclusion Criteria:

1. 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
2. Treatment for acute malnutrition, either as an inpatient or outpatient, within the past 3 months
3. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control Group; Standard weight-based dosing of Ready-to-Use Therapeutic Food (RUTF) at a dose of 150-200 kcal/kg/day	Drug: Amoxicillin; Standard weight-based dosing per Ehtiopian national guidelines; Dietary supplement: ready-to-use therapeutic food (RUTF); Standard formulation meeting UNICEF specifications: https://www.unicef.org/supply/sites/unicef.org.supply/files/2023-04/U239977-RUTF-Novel-Specification.pdf
Experimental: SAM Experimental A; 2 sachets (1000 kcal) of RUTF per day	Drug: Amoxicillin; Standard weight-based dosing per Ehtiopian national guidelines; Dietary supplement: ready-to-use therapeutic food (RUTF); Standard formulation meeting UNICEF specifications: https://www.unicef.org/supply/sites/unicef.org.supply/files/2023-04/U239977-RUTF-Novel-Specification.pdf
Experimental: SAM Experimental B; 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	Drug: Amoxicillin; Standard weight-based dosing per Ehtiopian national guidelines; Dietary supplement: ready-to-use therapeutic food (RUTF); Standard formulation meeting UNICEF specifications: https://www.unicef.org/supply/sites/unicef.org.supply/files/2023-04/U239977-RUTF-Novel-Specification.pdf

What is the study measuring?

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
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
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 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
MUAC gain 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 weight gain		up to 6 months post-recovery
medium-term MUAC gain		up to 6 months post-recovery

Collaborators and Investigators

• Sponsor: Action Against Hunger USA
• Collaborators: University of Washington; Ethiopian Public Health Institute
• Investigators: Principal Investigator: Indi Trehan, MD MPH DTM&H, University of Washington; Principal Investigator: Yosef B Asefaw, MSc, Ethiopian Public Health Institute; Principal Investigator: Heather C Stobaugh, PhD, Action Against Hunger USA

Study record dates

Study Major Dates

• Study Start (Estimated): September 25, 2023
• Primary Completion (Estimated): September 25, 2026
• Study Completion (Estimated): September 25, 2026

Study Registration Dates

• First Submitted: September 8, 2023
• First Submitted That Met QC Criteria: September 24, 2023
• First Posted (Actual): September 29, 2023

Study Record Updates

• Last Update Posted (Actual): September 29, 2023
• Last Update Submitted That Met QC Criteria: September 24, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Malnutrition; Severe Acute Malnutrition; Anti-Infective Agents; Anti-Bacterial Agents; Amoxicillin
• Other Study ID Numbers: MODAM-SAM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No