Study of Antioxidants and Oxidants in Malnourished Children

Study Overview
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Brief Summary
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It is believed that the organs of severely malnourished children malfunction because harmful compounds called oxidants injure the tissues in these organs. In a healthy person oxidants are made harmless because another compound called glutathione neutralizes them. Glutathione is made from three amino acids that we get from the protein we eat in our food. We found that malnourished children were not making enough glutathione because they lacked one of these amino acids called cysteine. In this study we determine why malnourished children do not have sufficient cysteine, and we will feed malnourished children a whey-based diet which is rich in cysteine during their treatment to determine whether they will make more glutathione. This in turn may make their organs recover faster. These findings will let us know whether malnourished children can recover faster if they are given more cysteine during the early phase of treatment.

Official Title
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Glutathione Homeostasis and Oxidant Damage in Kwashiorkor

Conditions
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Protein-energy Malnutrition, Kwashiorkor, Marasmus

Intervention / Treatment
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* Dietary Supplement: sulfur amino acids


Participation Criteria
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Eligibility Criteria
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Infants and toddlers, 6-18 months of age Suffering from severe protein-energy malnutrition, kwashiorkor and marasmic-kwashiorkor

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 18 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sulfur Amino Acids<br>12 children with edematous severe malnutrition will be assigned to receive 0.65 mmol/kg/d of sulfur amino acids. Supplements will be added to the children's daily diets. | Dietary Supplement: sulfur amino acids<br>* Sixteen (16) children with edematous SCU will be randomly assigned to either a supplement of SAA or an isonitrogenous amount of alanine<br>|
| Placebo Comparator: Alanine<br>12 children with edematous severe malnutrition are assigned to receive 0.65 mmol/kg/d of alanine as placebo. Supplements will be added to the children's daily diets. | Dietary Supplement: sulfur amino acids<br>* Sixteen (16) children with edematous SCU will be randomly assigned to either a supplement of SAA or an isonitrogenous amount of alanine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| small intestine, skin function and red blood cell gluathione synthesis | The effect of dietary supplementation with either a mixture of SAAs or alanine (controls) on: buccal tissue protein synthesis, small intestine structure, integrity and function (i.e. mixed mucosal and mucins protein synthesis rate, mucosal GSH synthesis and concentration, villous height and area and crypt depth, intestinal absorptive capacity and degree of mucosal leakiness, and synthesis of the starch digestive enzymes sucrase-isomaltase and maltase-glucoamylase, plus in vivo starch digestion and absorption) in groups of age- and gender-matched children with edematous SCU in the severely malnourished state. skin protein synthesis rate, rate of closure of skin lesions Red blood cell glutathione synthesis rate and cysteine production | after intervention | 
| immune capacity | synthesis rate of selected acute phase proteins | after intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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glutathione kinetics, oxidant damage, anti-oxidant capacity, oxidative stress, cysteine kinetics, severe childhood malnutrition