Effectiveness of Four Transition Dietary Regimens in the Hospital Management of Children With Kwashiorkor.
Condition: Severe Acute Malnutrition; Kwashiorkor; Nutritional Edema
MeSH terms: Malnutrition; Severe Acute Malnutrition; Kwashiorkor
Study type: Interventional

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®.
    

Intervention name(s): Standard F100; Standard F75 + Plumpynut; Alternative F75 with CMV + Plumpynut; Alternative F75 without CMV + Plumpynut
Intervention type(s): Dietary Supplement; Dietary Supplement; Dietary Supplement; Dietary Supplement
Intervention description(s): 100 kcal and 3 g protein per 100 ml; Standard F75 with ready to-use therapeutic food (Plumpynut); Alternative F75 containing CMV with ready to-use therapeutic food (Plumpynut); Alternative F75 with no CMV with ready to-use therapeutic food (Plumpynut)
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This is an open label randomized controlled trial to test the effectiveness of four diets in Kwashiorkor children in their transition phase.
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®.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Severe acute malnutrition; Nutritional rehabilitation; F100; Transition phase; Therapeutic complex of vitamins and minerals (CMV); Kwashiorkor; Ready-to-use Therapeutic Food