Clinical trial NCT05020847: Effectiveness of Alternative Diets During the Stabilization Phase on Children With Complicated SAM
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Severe Acute Malnutrition
Kwashiorkor
Nutritional Edema
Marasmus
Keywords: Severe acute malnutrition
Nutritional rehabilitation
F75
Stabilization phase
Therapeutic complex of vitamins and minerals (CMV)
Kwashiorkor
Marasmus
Lead sponsor: University Ghent
Sponsor class: OTHER
Collaborators: name: Institut de Recherche en Sciences de la Sante, Burkina Faso
name: University Hospital Sourô Sanou of Bobo Dioulasso (Burkina Faso)
name: Centre Muraz
First posted: 2021-08-25
Enrollment: 297
Sex: ALL
Minimum age (years): 6
Maximum age (years): 59
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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:

1. Standard F75;
2. Alternative F75 without CMV (mainly containing corn flour, sugar, powdered milk and oil); and
3. Alternative F75 with CMV (includes most minerals and vitamins like F75 and F100).
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Recovery rate of children
timeFrame: Three to Five days
measure: Daily weight gain
timeFrame: Three to Five days
measure: Number of days during the first phase of treatment
timeFrame: Three to Five days
Secondary outcomes:
measure: % of intake of the therapeutic regimen
timeFrame: Three to Five days
measure: Anorexia
timeFrame: Three to Five days
measure: Mortality
timeFrame: Three to Five days
measure: Diarrhea
timeFrame: Three to Five days
measure: Vomiting
timeFrame: Three to Five days
Other outcomes:
measure: HIV/AIDS
timeFrame: Three to Five days
measure: Hepatitis infection
timeFrame: Three to Five days
measure: Tuberculosis infection
timeFrame: Three to Five days
Locations:
city: Bobo-Dioulasso
country: Burkina Faso
facility: Centre Hospitalier Universitaire Souro
state: Bobo Dioulasso
Study officials:
affiliation: University Ghent
name: Stefaan De Henauw, Md. PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Ghent
name: Souheila Abbeddou, MSc. PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut de Recherche en Sciences de la Sante, Burkina Faso
name: Jerome Some, Md. PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Hospitalier Universitaire Souro, Bobo Dioulasso, Burkina Faso.
name: Bintou Sanogo, MSc. Md.
role: PRINCIPAL_INVESTIGATOR
References:
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citation: 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.