A double-blind clinical trial to compare the efficacy and safety of a multiple amino acid-based ORS with the standard WHO-ORS in the management of non-cholera acute watery diarrhea in infants and young children: “VS002A” trial protocol

Abstract

Background Diarrhea is the second deadliest disease for under-five children globally and the situation is more serious in developing countries. Oral rehydration solution (ORS) is being used as a standard treatment for acute watery diarrhea for a long time. Our objective is 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 is a randomized, double-blind, two-cell clinical trial at Dhaka Hospital of icddr,b. A total of 312 male children aged 6–36 months old with acute non-bloody watery diarrhea are included in this study. Intervention arm participants get amino acid-based ORS (VS002A) and the control arm gets standard glucose-based WHO-ORS. The primary efficacy endpoint is the duration of diarrhea in the hospital. Discussion Oral rehydration therapy (ORT) with the present ORS formulation has certain limitations - it does not reduce the volume, frequency, or duration of diarrhea. Additionally, the failure of present standard ORS to significantly reduce stool output likely contributes to the relatively limited use of ORS by mothers as they do not feel that ORS is helping their child recover from the episode of diarrhea. Certain neutral amino acids (e.g., glycine, L-alanine, L-glutamine) can enhance the absorption of sodium ions and water from the gut. By using this concept, a shelf-stable, sugar-free amino acid-based hydration medicinal food named ‘VS002A’ that effectively rehydrates, and improves the barrier function of the bowel following infections targeting the gastrointestinal tract has been developed. If the trial shows significant benefits of VS002A use, this may provide evidence to support consideration of the use of VS002A in the present WHO diarrhea management guidelines. Conversely, if there is no evidence of benefit, these results will reaffirm the current guidelines. Trial registration ClinicalTrials.gov NCT04677296. Registered on December 21, 2020.

Citrulline and kynurenine to tryptophan ratio: potential EED (environmental enteric dysfunction) biomarkers in acute watery diarrhea among children in Bangladesh

“…), a requirement of additional intravenous fluids after being provided with an IV for 4 h on admission if severely dehydrated, has documentation of taking antibiotics and/or antidiarrheal within the last 48 h before hospitalization. The study protocol is described in detail 60 .…”

“…Study design, study setting, and study population. The current analyses are based on data from a subsample of 102 participants enrolled in the VS002A clinical trial 60 . The VS002A trial is a randomized, doubleblind, two-cell superiority clinical trial comparing WHO-ORS and amino acid-based ORS: VS002A conducted in children, presenting with non-bloody acute non-cholera diarrhea with some dehydration in the Dhaka Hospital of icddr,b situated in Dhaka, capital of Bangladesh.…”