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

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

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.

Study Overview

• Status: Completed
• Conditions: Severe Acute Malnutrition; Kwashiorkor; Marasmus; Nutritional Edema
• Intervention / Treatment: Dietary supplement: Standard F75; Dietary supplement: Alternative F75 with CMV; Dietary supplement: Alternative F75 without CMV

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 297
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Burkina Faso
  • Bobo Dioulasso
    • Bobo-Dioulasso, Bobo Dioulasso, Burkina Faso
      • Centre Hospitalier Universitaire Souro

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 4 years (Child)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard F75; 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; F-75 contains 75 kcal and 0.9 g protein per 100 ml
Experimental: Alternative F75 with CMV; 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; Alternative F75 With CMV contains cereal flour, oil, sugar, powdered milk with complex mineral-vitamin (CMV)
Experimental: Alternative F75 without CMV; 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; Alternative F75 without CMV contains cereal flour, oil, sugar, powdered milk without complex mineral vitamin (CMV).

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
HIV/AIDS	Detection of HIV/AIDS using polymerase chain reaction (PCR) in infants and children younger than 18 months or retroviral serology test in older children.	Three to Five days
Hepatitis infection	Blood test of hepatitis using the enzyme-linked immunosorbent assay (ELISA)	Three to Five days
Tuberculosis infection	Test of tuberculosis via search for Koch's Bacillus in gastric/spit tubing and molecular testing of stools using polymerase chain reaction (PCR)	Three to Five days

Collaborators and Investigators

• Sponsor: University Ghent
• Collaborators: Institut de Recherche en Sciences de la Sante, Burkina Faso; Centre Muraz; University Hospital Sourô Sanou of Bobo Dioulasso (Burkina Faso)
• Investigators: Principal Investigator: Stefaan De Henauw, Md. PhD, University of Ghent; Principal Investigator: Souheila Abbeddou, MSc. PhD, University of Ghent; Principal Investigator: Jerome Some, Md. PhD, Institut de Recherche en Sciences de la Sante, Burkina Faso; Principal Investigator: Bintou Sanogo, MSc. Md., Centre Hospitalier Universitaire Souro, Bobo Dioulasso, Burkina Faso.

Publications and helpful links

General Publications

• Bartz S, Mody A, Hornik C, Bain J, Muehlbauer M, Kiyimba T, Kiboneka E, Stevens R, Bartlett J, St Peter JV, Newgard CB, Freemark M. Severe acute malnutrition in childhood: hormonal and metabolic status at presentation, response to treatment, and predictors of mortality. J Clin Endocrinol Metab. 2014 Jun;99(6):2128-37. doi: 10.1210/jc.2013-4018. Epub 2014 Feb 27.
• Deen JL, Funk M, Guevara VC, Saloojee H, Doe JY, Palmer A, Weber MW. Implementation of WHO guidelines on management of severe malnutrition in hospitals in Africa. Bull World Health Organ. 2003;81(4):237-43. Epub 2003 May 16.
• Gopalan C. Kwashiorkor and marasmus: evolution and distinguishing features. 1968. Natl Med J India. 1992 May-Jun;5(3):145-51. No abstract available.
• Nguefack F, Adjahoung CA, Keugoung B, Kamgaing N, Dongmo R. [Hospital management of severe acute malnutrition in children with F-75 and F-100 alternative local preparations: results and challenges]. Pan Afr Med J. 2015 Aug 31;21:329. doi: 10.11604/pamj.2015.21.329.6632. eCollection 2015. French.
• Singh K, Badgaiyan N, Ranjan A, Dixit HO, Kaushik A, Kushwaha KP, Aguayo VM. Management of children with severe acute malnutrition: experience of Nutrition Rehabilitation Centers in Uttar Pradesh, India. Indian Pediatr. 2014 Jan;51(1):21-5. doi: 10.1007/s13312-014-0328-9. Epub 2013 Jul 5.

Helpful Links

• World Health Organization (2013) WHO guideline: updates on the management of severe acute malnutrition in infants and children.
• Enquête Nutritionnelle Nationale SMART 2016 au Burkina Faso. 2016 ; 47p
• Ministère de la Sante au Burkina Faso. Protocol National : Prise en charge intégrée de la malnutrition aigüe (PCIMA). 2014

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2021
• Primary Completion (Actual): August 31, 2023
• Study Completion (Actual): August 31, 2023

Study Registration Dates

• First Submitted: August 2, 2021
• First Submitted That Met QC Criteria: August 24, 2021
• First Posted (Actual): August 25, 2021

Study Record Updates

• Last Update Posted (Actual): October 30, 2023
• Last Update Submitted That Met QC Criteria: October 27, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Severe acute malnutrition; Nutritional rehabilitation; F75; Stabilization phase; Kwashiorkor; Marasmus; Therapeutic complex of vitamins and minerals (CMV)
• Additional Relevant MeSH Terms: Nutrition Disorders; Deficiency Diseases; Protein Deficiency; Malnutrition; Severe Acute Malnutrition; Protein-Energy Malnutrition; Kwashiorkor
• Other Study ID Numbers: BC-09443-A

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All the data that can affect the main or the secondary outcomes will be used in the analyses and shared as necessary.

Drug and device information, study documents

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