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Effectiveness of Four Transition Dietary Regimens in the Hospital Management of Children With Kwashiorkor.

Not Applicable
Completed
Conditions
Kwashiorkor
Severe Acute Malnutrition
Nutritional Edema
Interventions
Dietary Supplement: Standard F100
Dietary Supplement: Standard F75 + Plumpynut
Dietary Supplement: Alternative F75 with CMV + Plumpynut
Dietary Supplement: Alternative F75 without CMV + Plumpynut
Registration Number
NCT05015257
Lead Sponsor
University Ghent
Brief Summary

In Burkina Faso the number of severely acute malnourished (SAM) children successfully treated has increased since the implementation of community-based management of acute malnutrition. SAM children with oedema have a higher risk of dying than SAM without oedema; they require inpatient care. Several theories have been proposed to explain the pathophysiology of oedema in SAM, but its etiology remains unclear. Knowledge on the nutritional adequacy of therapeutic regimens in kwashiorkor is limited. The World Health Organization (WHO) recommends to use in the treatment of complicated SAM a therapeutic milk 'F75' in the stabilization phase; F75+ready-to-use therapeutic foods (RUTF) or F100 at the transition phase. Alternatively the local formulas (maize flour, milk powder, oil, sugar, mineral-vitamin complex CMV) can be used in case of shortage or intolerance.

At the Nutritional Rehabilitation and Education Center of the University Hospital of Bobo Dioulasso it was found that some SAM children whose oedema resolved under F75 in the stabilization phase, re-developed oedema as they entered the transition phase with RUTF. RUTF has the same nutritional value as F100 but contains iron unlike F100 (\<0.07 mg/100 mL). It was observed that RUTF in some cases may be associated with higher mortality, probably due to high iron content (10-14 mg/100 g), which may increase the risk of infections and the formation of free radicals, thereby increasing damage to the body's cells. Clinical trials evaluating the current guidelines for the treatment of SAM with oedema are scarce. A better understanding of the risk factors affecting the effectiveness of the nutritional therapeutic protocol for children with Kwashiorkor will be useful to improve their care.

The main objective of this study is to determine whether the use of transition phase diets (Plumpy-Nut®+F75 or F100 or alternative F75+/- CMV+ Plumpy-Nut®) affect oedema resolving in Kwashiorkor children and to investigate the underlying factors for the relapse or non-responsiveness to the therapeutic treatment.

Detailed Description

Severe acute malnutrition (SAM) is a life threatening condition that requires urgent attention and appropriate management to reduce mortality and promote recovery among children. SAM is defined by 1) a weight-for-height Z-score more than three standard deviations (SD) below the median based on the 2006 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 (SAM with edema) is one of the forms of complicated SAM commonly distinguished by the unmistakable presence of bipedal edema. Kwashiorkor is characterized by the following clinical signs: 1) edemas symmetrical, painless, soft, bilateral, ascending, pitting; 2) lesions of the skin and integuments; 3) ulcerations and depigmentation; 4) alopecia; 5) constant weight loss marked by edema; 6) hepatomegaly; 7) clinical anemia; 8) intestinal transit disorders: persistent diarrhea, vomiting; 9) anorexia and behavioral disorders (apathy).

Severe acute malnutrition 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.

The objective of this study is to determine whether the use of different transition phase diets affect oedema resolving in Kwashiorkor children and to investigate the underlying factors for the relapse or non-responsiveness to the therapeutic treatment.

Hypotheses to be tested

* The first hypothesis is that RUTF (Plumpy-Nut®) because of its content in iron may compromise the effectiveness of the transition phase in children with kwashiorkor

* The second hypothesis is that underlying factors including co-morbidities and epigenetics may explain a difference in response to therapeutic regimens

This is an open label randomized controlled trial to test the effectiveness of four used transition phase diets in Kwashiorkor children in their transition to the rehabilitation phase. The four dietary regimens that will be tested are:

1. F100;

2. RUTF+F75;

3. RUTF+alternative F75 with complex mineral-vitamin (CMV); and

4. RUTF+alternative F75 without CMV.

When it is decided to move to the transition phase, the child will be assigned to one of the treatments depending on the treatment received during the stabilization phase and the results of the appetite test. That is a child who accepts the Plumpy Nut will receive it in combination with their regimen they had during the stabilization phase. If a child does not accept Plumpy Nut, then they will received F100 regardless of their initial therapeutic food regimen.

* For those who received F75 in the stabilization phase, they will receive standard F75 + Plumpy Nut

* For those who received alternative F75 with CMV in the stabilization phase, they will receive alternative F75 with CMV + Plumpy Nut®

* For those who received alternative F75 without CMV in the stabilization phase, they will receive alternative F75 without CMV + Plumpy Nut®.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
32
Inclusion Criteria
  • Severe acute malnutrition defined as the presence of edema
  • Who are admitted and treated in the refeeding center (CREN) of the CHUSS
  • Aged between 6 and 59 Months
  • Parental Signed informed consent form
  • Recruited in the first phase of the treatment and successfully admitted to the transition phase
Exclusion Criteria
  • SAM without edema
  • Moderate acute malnutrition (MAM)
  • Did not improve during the stabilization phase

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Standard F100Standard F100If the test of appetite at the end of the stabilization phase is negative (the child does not accept the Plumpynut)
Standard F75+PlumpynutStandard F75 + PlumpynutIf the test of appetite at the end of the stabilization phase is positive (the child accepts the Plumpynut) and the child received Standard F75 during the stabilization phase
Alternative F75 with CMV +PlumpynutAlternative F75 with CMV + PlumpynutIf the test of appetite at the end of the stabilization phase is positive (the child accepts the Plumpynut) and the child received Alternative F75 with CMV during the stabilization phase
Alternative F75 without CMV +PlumpynutAlternative F75 without CMV + PlumpynutIf the test of appetite at the end of the stabilization phase is positive (the child accepts the Plumpynut) and the child received Alternative F75 without CMV during the stabilization phase
Primary Outcome Measures
NameTimeMethod
Severe adverse eventThree to Seven days

Any serious severe adverse event ranging from diarrhea, vomiting, anorexia to death

Edema redevelopment during the transition phaseThree to Seven days

Number of children whose edema redeveloped after it has been resolved during the stabilization phase

Secondary Outcome Measures
NameTimeMethod
EpigeneticsThree to Seven days

In a subsample of children, DNA methylation is identified using Illumina Array Analysis Platform

Soil HelminthsThree to Seven days

Determination of intestinal parasites using Quantitative Real-Time polymerase chain reaction (qPCR)

Mean number of days for a complete edema resolvingThree to Seven days

Number of days for a complete edema resolving among Kwashiorkor children, in Day

Intestinal microbiotaThree to Seven days

16S rRNA sequencing of DNA extracts of fecal samples

Presence of acidic stoolsThree to Seven days

Measurement of stool potential Hydrogen (pH)

Trial Locations

Locations (1)

Centre Hospitalier Universitaire Souro

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Bobo-Dioulasso, Bobo Dioulasso, Burkina Faso

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