Effectiveness of Alternative Diets During the Stabilization Phase on Children With Complicated SAM

Study Overview
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Brief Summary
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Severe acute malnutrition (SAM) is a life threatening condition and is defined by 1) a weight-for-height Z-score more than three standard deviations (SD) below the median based on the 2006 World Health Organization (WHO) growth standards, 2) a mid-upper arm circumference (MUAC) of less than 115 mm or 3) by the presence of nutritional edema. Signs such as edema, mucocutaneous changes, hepatomegaly, lethargy, anorexia, anemia, severe immune deficiency and rapid progression to mortality characterize a state commonly coined as complicated SAM. Kwashiorkor is one of the forms of complicated SAM commonly distinguished by the unmistakable presence of bipedal edema. SAM results in high mortality rates of up to half a million child deaths annually. Undernourished children are at higher risk of mortality ranging from three times more risk among children with moderate malnutrition to 10-times in SAM children compared to well-nourished children. Children with complicated SAM require inpatient treatment in specialized centers. The Rehabilitation and Nutritional Education Center (CREN) is a specialized center in Burkina Faso receiving on average 10 SAM children per day. Recovery rate is lower than international standards; and adverse events and mortality remain strikingly high. Our main objective is to assess the underlying risk factors affecting the effectiveness of the nutritional therapeutic treatment protocol for complicated SAM children under 5 years of age who have been referred to the CREN, at the Centre Hôspitalier Universitaire Souro, Bobo Dioulasso, Burkina Faso. The specific objective is to assess the effectiveness of alternative dietary regimens during the stabilization phase on well-specified clinical and biochemical outcomes in children with complicated SAM. Dietary regimens differ by their carbohydrate profile and content, and by their different micronutrient composition including vitamin A, iron and zinc.

Detailed Description
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Severe acute malnutrition (SAM), defined as severe wasting [weight-to-height Z-score < -3 standard deviations (SD), based on the WHO Child Growth Standards] and / or the presence of nutritional edema, and / or mid-upper arm circumference (MUAC) <115 mm, is a condition that requires urgent attention and appropriate management to reduce mortality and promote recovery among children. Management of SAM children without complications is provided at the community level. Hospitalization in specialized care centers is necessary for SAM children with complications. SAM children with comorbidities have a greater risk of mortality and treatment failure. Our knowledge of the specific adequate nutritional needs of SAM is limited. For the treatment of SAM in hospital, the WHO recommends the use of therapeutic milk low in protein 'F75' in the stabilization phase; and more protein-rich F100 or F75 combined with ready-to-use therapeutic foods (RUTF) in the transition phase. The WHO also recommends using as an alternative formula made of cereal flour, skimmed milk powder, oil, sugar, and a therapeutic vitamin and mineral complex (CMV), in case of shortage of the standard therapeutic milk F75 / F100 or in case of signs of intolerance (vomiting, diarrhea). The Refeeding Center - Centre de Récupération et d'Education Nutritionnelle (CREN) of the Sourô Sanou University Hospital Center (CHUSS) in Burkina Faso specializes in the care of SAM children with complications. In 2018, out of 500 children aged 6-59 months admitted for SAM with complications, the CHUSS CREN registered 86.8% full recovery, 8.2% dropout and 5% death. Although the recovery rate is higher than international standards (greater than 75%), the mortality rate remains higher than the recommended 3% by international standards; in addition to the challenges that are faced locally in maintaining high standards of care. At the CREN, we observed that some SAM children with complications can have severe diarrhea and vomiting after taking F75 (first phase of the nutritional treatment). It was also observed that other SAM children with edema, whose edema resolved in the first phase of treatment under F75, redeveloped edema when they received RUTF (Plumpy Nut®) in the transition phase according to the WHO 2013 protocol. The second objective of the study is to assess the risk factors affecting the response to dietary treatment in this center (the CREN, Burkina Faso) and to compare alternatives for treatment during the nutritional rehabilitation. Problematic It was observed at the Refeeding Center (CREN) of the Sourô Sanou University Hospital (CHUSS) in Bobo Dioulasso, that SAM children with complications show during their treatment, signs of intolerance to F75 (diarrhea , vomiting). The pathophysiology of diarrhea in SAM involves several theories including that of lactose intolerance, and that of alteration of the intestinal microbiota. The study aims to assess the effectiveness of diet regimens [standard F75, or alternative F75 + mineral vitamin complex (CMV), or alternative F75 without CMV] during the stabilization phase from both a clinical and biochemical aspects in children with complicated SAM. Diets differ in their profile and carbohydrate content, and in their different micronutrient compositions, including vitamin A, iron and zinc. Our hypothesis is that the F75 alternative during the stabilization phase (the first phase) of complicated SAM children is associated with better compliance, less diarrhea and better outcomes than the recommended F75 formulation; and that children treated correctly with the F75 alternative containing CMV will perform better than the other two groups of children treated with F75 or the F75 alternative without CMV. This will be an open, randomized controlled trial aimed at testing the effectiveness of three therapeutic diet regimens during the first phase of hospital management of children with complicated SAM admitted to CREN, Bobo Dioulasso. After obtaining informed consent from parents / guardians for the inclusion of the child, the child will be randomized and will receive their assigned treatment. In accordance with the 2014 protocol for the management of SAM in Burkina Faso, an antibiotic will be given as part of the systematic treatment of complicated SAM, and other medical treatments depending on the associated complication. Deworming is provided also gratis, will be done only in children whose tests are positive for intestinal parasites and ONLY in the rehabilitation phase (the third phase of the treatment) as per the National Protocol for the management of complicated SAM. The dietetic treatment will be given by the nurses every 2 hours on the first day; then if tolerance is good, every 3 hours the following days. No family meals during phase 1. But the baby can breastfeed. The observance and tolerance of the treatment will be noted by the nurses: amount of milk taken, refusal, vomiting, diarrhea, presence of a nasogastric tube. The quantities will be given according to the weight of the child, the presence or not of edema, in accordance with the national protocol.

Official Title
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The Underlying Causes Affecting the Response to Dietary Rehabilitation in Severely Acutely Malnourished Children at the Center Hôspitalier Universitaire Sourô Sanou, Bobo Dioulasso, Burkina Faso

Conditions
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Severe Acute Malnutrition, Kwashiorkor, Nutritional Edema, Marasmus

Intervention / Treatment
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* Dietary Supplement: Standard F75
* Dietary Supplement: Alternative F75 with CMV
* Dietary Supplement: Alternative F75 without CMV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Severe acute malnutrition defined as Weight-for-Height Z-score (WHZ) <- 3 SD AND / OR MUAC <115 mm AND / OR with edema With complications Who are admitted and treated in the refeeding center (CREN) of the CHUSS Aged between 6 and 59 Months Parental Signed informed consent form Exclusion Criteria: Children younger than 6 months or older than 59 months of age Moderate Acute Malnutrition (MAM)

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: This will be an open, randomized controlled trial aimed at testing the effectiveness of three therapeutic diet regimens during the first phase of hospital management of children with complicated SAM admitted to CREN, Bobo Dioulasso. Children aged 6 to 59 months hospitalized in the pediatric department or other services of the Bobo Dioulassso CHUSS, and admitted to the CREN for complicated SAM (WHZ < -3 SD and/or MUAC < 115 mm and/or the presence of nutritional edema) will be randomly assigned to receive: Standard F75; Alternative F75 without CMV (mainly containing corn flour, sugar, powdered milk and oil); and Alternative F75 with CMV (includes most minerals and vitamins like F75 and F100).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard F75<br>At the admission, therapeutic food is given by the nurses every 2 hours on the first day; then if tolerance is good, every 3 hours the following days. No family meals during the stabilization phase. But the baby can breastfeed. A child will receive an antibiotic as per the national protocol, malaria treatment if diagnosed with malaria, Vitamin A if symptomatic eye damage, Folic acid in case of anemia, antifungal in case of candidiasis. | Dietary Supplement: Standard F75<br>* F-75 contains 75 kcal and 0.9 g protein per 100 ml<br>|
| Experimental: Alternative F75 with CMV<br>At the admission, therapeutic food is given by the nurses every 2 hours on the first day; then if tolerance is good, every 3 hours the following days. No family meals during the stabilization phase. But the baby can breastfeed. A child will receive an antibiotic as per the national protocol, malaria treatment if diagnosed with malaria, Vitamin A if symptomatic eye damage, Folic acid in case of anemia, antifungal in case of candidiasis. | Dietary Supplement: Alternative F75 with CMV<br>* Alternative F75 With CMV contains cereal flour, oil, sugar, powdered milk with complex mineral-vitamin (CMV)<br>|
| Experimental: Alternative F75 without CMV<br>At the admission, therapeutic food is given by the nurses every 2 hours on the first day; then if tolerance is good, every 3 hours the following days. No family meals during the stabilization phase. But the baby can breastfeed. A child will receive an antibiotic as per the national protocol, malaria treatment if diagnosed with malaria, Vitamin A if symptomatic eye damage, Folic acid in case of anemia, antifungal in case of candidiasis. | Dietary Supplement: Alternative F75 without CMV<br>* Alternative F75 without CMV contains cereal flour, oil, sugar, powdered milk without complex mineral vitamin (CMV).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recovery rate of children | Number of children treated and admitted to the transition phase | Three to Five days | 
| Daily weight gain | Average daily weight gain in the stabilization phase in Grams | Three to Five days | 
| Number of days during the first phase of treatment | Average number of days spent in the stabilization phase in Day | Three to Five days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| % of intake of the therapeutic regimen | Daily intake of the administered dietary treatment | Three to Five days | 
| Anorexia | Serious severe event that occurs at anytime during the treatment | Three to Five days | 
| Mortality | Serious severe event that occurs at anytime during the treatment | Three to Five days | 
| Diarrhea | Serious severe event that occurs at anytime during the treatment | Three to Five days | 
| Vomiting | Serious severe event that occurs at anytime during the treatment | Three to Five days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Severe acute malnutrition, Nutritional rehabilitation, F75, Stabilization phase, Therapeutic complex of vitamins and minerals (CMV), Kwashiorkor, Marasmus