Clinical Trial to Compare the Efficacy and Safety of a Multiple Amino-acid Based ORS "VS002A" With the Standard WHO-ORS in the Management of Noncholera Acute Watery Diarrhea in Infants and Young Children

Background (brief):

1. Burden: Diarrhea is the second deadliest disease for under-five children globally and the situation is more serious in developing countries. It was responsible for 688 million illnesses and 499,000 deaths worldwide in children less than 5 years of age in 2015 (Kotloff, 2017). Majority of the deaths from diarrhea occur before the second birthday of the children and it contributes to more than 20% of overall death in infants and young children.
2. Knowledge gap: Oral rehydration solution (ORS) is being used as a standard treatment for acute watery diarrhea for long time and which is one of the best inventions in the history of medicine. The ORS currently recommended by the WHO/UNICEF contains glucose, sodium chloride, potassium chloride, and tri-sodium citrate dehydrate, which is optimal for rehydration of patients of all ages with dehydration from acute diarrhea of any aetiology. However, oral rehydration therapy (ORT) with the present ORS formulation has certain limitations - it does not reduce the volume, frequency or the duration of diarrhea. Additionally, the failure of present standard ORS to reduce dramatically stool output likely contributes to the relatively limited use of ORS by mothers as they do not feel that ORS is helping their child from the episode of diarrhea. Thus, it warrants the development of newer and improved formulation of ORS to become more effective against diarrhea.
3. Relevance: It has been reported that the glucose contained in standard ORS may fail to absorb fluid and electrolytes adequately from gut and worsen diarrhea in different patho-physiological ways as the present WHO ORS is hypo-osmolar. Whereas, certain neutral amino acids (e.g. glycine, L-alanine, L-glutamine) are able to enhance the absorption of sodium ions and water from gut. By using this concept, the University of Florida (UF), developed a sugar-free, shelf-stable amino acid-based hydration medicinal food named 'VS002A' that effectively rehydrates, and improves barrier function of the bowel following infections targeting the gastrointestinal tract. So, the investigators ought to know whether VS002A will be superior or not to WHO-ORS in the treatment of acute non-cholera watery diarrhea in infants and young children.

Hypothesis (if any): The amino acid-based ORS "VS002A" will reduce duration of non-cholera watery diarrhea in infants and young children when compared to treatment with standard WHO-ORS.

Objectives: To compare the efficacy of amino acid-based ORS "VS002A" compared to standard Glucose-based WHO ORS in infants and young children suffering from acute non-cholera watery diarrhea.

Methods:

• It will be a randomized, double-blind, two cell clinical trial at Dhaka Hospital of icddr,b. Total 312 (156 in each arm) male children aged 6-36 months old with acute (onset <48 hours) non-bloody watery diarrhea will be included in this study. However, patients with severe malnutrition, any systemic illness, cholera, unwilling to comply with study protocol, remain significantly dehydrated 4 hours after intravenous fluid infusion (if required at start), has documentation of taking antibiotics or antidiarrheal 48 hours before admission will be excluded.
• Intervention arm participants will get amino acid ORS (VS002A) and control arm will get standard glucose based WHO-ORS. Other aspects of clinical managements for diarrhea as per hospital guideline will be similar in both cases and controls