Exploratory Study to Evaluate the Effect of L-isoleucine Supplemented Oral Rehydration Solution in the Treatment of Acute Diarrhoea in Children and in Inducing Innate Immunity
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 50
- Locations
- 2
- Primary Endpoint
- 1. Weight of abnormal (watery/liquid) stool for each 6-hour and 24-hour (day) of the study as well as cumulative weight until resolution of diarrhoea (maximum of 5 days)
Study Overview
Brief Summary
Efforts are continuing to improve the efficacy of oral rehydration solution in terms of reducing the severity (stool volume) and duration of diarrhoea (enhancement of recovery). Antimicrobial peptides, produced by the epithelial cells, represent an important component of the innate immunity of all epithelial surfaces of the body including intestine. Induction of expression of antimicrobial peptides on epithelial cell surface, may thus hasten recovery from infectious diarrhoea. Isoleucine is an essential amino acid that is easily available and not very expensive, and its addition to oral rehydration solution might help early clearance of diarrhoeal pathogen by inducing secretion of antimicrobial peptide by the small intestinal epithelial cells. Additionally, it is expected to hasten recovery from diarrhoea by reestablishing the commensal bacteria. The aim of this pilot study is to assess if addition of isoleucine to oral rehydration solution induces secretion of antimicrobial peptide, help establish normal bacterial populations in the intestine, and favourably impacts the severity and duration of diarrhoea in young children. If the results are found encouraging, a therapeutic trial with adequate sample size would be justified.
Detailed Description
Globally, diarrhoea still accounts for 1.6 to 2.5 million deaths annually, and children in the developing world experience an average of 3 episodes of diarrhoea each year. Despite the decline in diarrhoeal mortality, it remains a leading cause of childhood morbidity and deaths [1]. Prevention of dehydration using appropriate home-made fluids or ORS solution, and correction of dehydration using ORS solution or intravenous fluid as indicated followed by maintenance of hydration using ORS solution, along with continuation of usual food including breastfeeding are most important elements of management of acute diarrhea. Antimicrobial therapy is recommended in the management of a few specific etiologic diarrhoeas such as severe cholera, shigellosis, invasive intestinal amoebiasis, and symptomatic giardiasis. The cost of therapy and more importantly the emergence of resistance pathogens are the major concerns for antimicrobial therapy for diarrhoea as for other bacterial infections.
ORS plays a major role in the treatment diarrhoeal diseases; however, it does neither reduce the severity nor the duration of diarrhoea, its major limitations. Efforts are continuing to overcome these limitations by developing newer formulations and delivery mechanisms e.g.
- Changing/replacing the substrates (e.g. addition of alanine or glycine to glucose or replacing glucose by multodextrin and rice powder)
- Reducing the concentration of glucose and sodium and thus osmolarity of ORS solution.
Alanine/glycine and rice powder containing ORS demonstrated some reduction in the stool output [2-5]. However, none of the formulations developed and tested till date demonstrated any beneficial effect on the duration of diarrhoea. Similarly, reduced osmolarity ORS has some beneficial effect on reducing the stool output and vomiting, and reducing failure of ORT mainly in children with non-cholera diarrhea, but did not have any effect on the diarrhoea duration [6]. The World Health Organization (WHO) and the United Nations Children Fund (UNICEF) have recently recommended routine use of the reduced-osmolarity ORS in the management of diarrhoeal diseases [7]; however, there are scopes to further improve its efficacy.
Antimicrobial peptides and innate immunity
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 6 Months to 36 Months (Child)
- Sex
- Male
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age: 6 months-36 months
- •Sex: only males, for precise separation of stool and urine
- •History of diarrhoea duration of <48 hours
- •Dehydration: some
Exclusion Criteria
- •Diarrhoea due to Vibrio cholerae that requires antimicrobial therapy by dark field microscopy
- •Dysentery (blood in stool), which requires antimicrobial therapy
- •Concomitant infection(s) e.g. ARI, meningitis, and sepsis
- •History of taking antibiotics for the current diarrhoea episode
- •Severely malnourished children (Wt for length < 70%) or patients with edema
Outcomes
Primary Outcomes
1. Weight of abnormal (watery/liquid) stool for each 6-hour and 24-hour (day) of the study as well as cumulative weight until resolution of diarrhoea (maximum of 5 days)
Time Frame: 12 months
Secondary Outcomes
- 1. ORS intake in different time periods, for each 6-hour and 24-hour (day) of the study as well as cumulative weight until resolution of diarrhoea (maximum of 5 days)(12 months)